Trials

Evaluating the effectiveness of early urethral catheter removal combined with intermittent catheterization for promoting early recovery of bladder function after laparoscopic radical hysterectomy: a study protocol for a randomized controlled trial

Abstract Background Bladder dysfunction, notably urinary retention, emerges as a significant complication for cervical cancer patients following radical hysterectomy, predominantly due to nerve damage, severely impacting their postoperative quality of life. The challenges to recovery include insufficient pelvic floor muscle training and the negative effects of prolonged postoperative indwelling urinary catheters. Intermittent catheterization represents the gold standard for neurogenic bladder management, facilitating bladder training, which is an important behavioral therapy aiming to enhance bladder function through the training of the external urethral sphincter and promoting the recovery of the micturition reflex. Nevertheless, gaps remain in current research regarding optimal timing for intermittent catheterization and the evaluation of subjective symptoms of bladder dysfunction. Methods Cervical cancer patients undergoing laparoscopic radical hysterectomy will be recruited to this randomized controlled trial. Participants will be randomly assigned to either early postoperative catheter removal combined with intermittent catheterization group or a control group receiving standard care with indwelling urinary catheters. All these patients will be followed for 3 months after surgery. The study’s primary endpoint is the comparison of bladder function recovery rates (defined as achieving a Bladder Function Recovery Grade of II or higher) 2 weeks post-surgery. Secondary endpoints include the incidence of urinary tract infections, and changes in urodynamic parameters, and Mesure Du Handicap Urinaire scores within 1 month postoperatively. All analysis will adhere to the intention-to-treat principle. Discussion The findings from this trial are expected to refine clinical management strategies for enhancing postoperative recovery among cervical cancer patients undergoing radical hysterectomy. By providing robust evidence, this study aims to support patients and their families in informed decision-making regarding postoperative bladder management, potentially reducing the incidence of urinary complications and improving overall quality of life post-surgery. Trial registration ChiCTR2200064041, registered on 24th September, 2022.

The SHOW RESPECT adaptable framework of considerations for planning how to share trial results with participants, based on qualitative findings from trial participants and site staff

Abstract Background Sharing trial results with participants is a moral imperative, but too often does not happen in appropriate ways. Methods We carried out semi-structured interviews with patients (n = 13) and site staff (n = 11), and surveyed 180 patients and 68 site staff who were part of the Show RESPECT study, which tested approaches to sharing results with participants in the context of the ICON8 ovarian cancer trial (ISRCTN10356387). Qualitative and free-text data were analysed thematically, and findings used to develop the SHOW RESPECT adaptable framework of considerations for planning how to share trial results with participants. This paper presents the framework, with illustrations drawn from the Show RESPECT study. Results Our adaptable ‘SHOW RESPECT’ framework covers (1) Supporting and preparing trial participants to receive results, (2) HOw will the results reach participants?, (3) Who are the trial participants?, (4) REsults—what do they show?, (5) Special considerations, (6) Provider—who will share results with participants?, (7) Expertise and resources, (8) Communication tools and (9) Timing of sharing results. While the data upon which the framework is based come from a single trial, many of our findings are corroborated by findings from other studies in this area, supporting the transferability of our framework to trials beyond the UK ovarian cancer setting in which our work took place. Conclusions This adaptable ‘SHOW RESPECT’ framework can guide researchers as they plan how to share aggregate trial results with participants. While our data are drawn from a single trial context, the findings from Show RESPECT illustrate how approaches to communication in a specific trial can influence patient and staff experiences of feedback of trial results. The framework generated from these findings can be adapted to fit different trial contexts and used by other researchers to plan the sharing of results with their own participants. Trial registration ISRCTN96189403. Registered on February 26, 2019. Show RESPECT was supported by the Medical Research Council (MC_UU_12023/24 and MC_UU_00004/08) and the NIHR CRN.

Direct letters to relatives at risk of hereditary cancer—study protocol for a multi-center randomized controlled trial of healthcare-assisted versus family-mediated risk disclosure at Swedish cancer genetics clinics (DIRECT-study)

Abstract Background The results of germline genetic testing for hereditary cancer are of importance not only to the patients under investigation but also to their genetic at-risk relatives. Standard care is to encourage the proband (first family member under investigation) to pass on this risk information to the relatives. Previous research suggests that with family-mediated disclosure, only about a third of at-risk relatives contact health care to receive genetic counselling. In some studies, complementing family-mediated risk disclosure with healthcare-assisted risk disclosure almost doubles the uptake of genetic counselling in at-risk relatives. In this study, we evaluate healthcare-assisted direct letters to relatives at risk of hereditary cancer syndromes in a randomized controlled trial. Methods Probands are recruited from Swedish outpatient cancer genetics clinics to this two-arm randomized controlled trial. The study recruits probands with either a pathogenic variant in a cancer susceptibility gene ( BRCA1 , BRCA2 , PALB2 , MLH1 , MSH2 , MSH6 , PMS2 ) or probands with familial breast and colorectal cancer based on clinical and pedigree criteria. In both arms, probands receive standard care, i.e., are encouraged and supported to pass on information to relatives. In the intervention arm, the proband is also offered to have direct letters sent to the at-risk relatives. The primary outcome measure is the proportion of at-risk relatives contacting a Swedish cancer genetics clinic within 12 months of the proband receiving the test results. Discussion This paper describes the protocol of a randomized controlled clinical trial evaluating a healthcare-assisted approach to risk disclosure by offering the probands to send direct letters to their at-risk relatives. The results of this study should be informative in the future development of risk disclosure practices in cancer genetics clinics. Trial registration ClinicalTrials.gov. Identifier NCT04197856 (pre-trial registration on December 13, 2019). Also registered at the website “RCC Cancerstudier i Sverige” as study #86719.

HPV self-sampling for cervical cancer screening among women living with HIV in Ghana: protocol for a hybrid type 1 effectiveness-implementation randomized controlled trial

Women living with HIV (WLWH) face a significantly higher risk of developing cervical cancer (CC) due to immune system suppression, which impairs the body's ability to clear high-risk HPV infections. Despite this increased risk, cervical cancer screening rates remain low among WLWH in Ghana, hindered by financial, logistical, and cultural barriers. Evidence-based interventions, such as HPV self-sampling and the 3R communication model (reframe, reprioritize, and reform) offer promising strategies to improve screening uptake. The primary objective of this study was to evaluate the effectiveness of the Home-based self-sampling for cervical cancer Prevention Education (HOPE) toolkit in increasing CC screening among WLWH in Ghana. Secondary objectives include assessing the feasibility, acceptability, appropriateness and adoptability of the HOPE intervention, as well as identifying key factors that influence its implementation. The study will be conducted at the Cape Coast Teaching Hospital (CCTH) in Ghana, using a Hybrid Type 1 effectiveness-implementation randomized controlled trial (RCT) design. A total of 108 WLWH will be randomly assigned to either the HOPE intervention group, which includes HPV self-sampling and 3R messaging, or a control group receiving standard care. Data will be collected through structured surveys, key informant interviews, and focus group discussions. The study will also engage a stakeholder advisory board (SAB) comprising WLWH, healthcare providers and community members to co-develop and adapt the intervention through nominal group technique. By leveraging existing healthcare infrastructure and community engagement, this study seeks to provide a scalable, evidence-based approach to improving CC screening among WLWH in Ghana. Findings will inform national strategies for integrating HPV self-sampling and health communication interventions to enhance early detection and reduce cervical cancer-related morbidity and mortality in this high-risk population. ClinicalTrials.gov NCT06739772. Registered on 18 December 2024.

Prophylactic para-aortic irradiation vs pelvic radiotherapy in pelvic node-positive carcinoma cervix in the setting of concurrent chemoradiation: a phase II open-label multi centric randomized controlled trial (PRO-PARA)

EMBRACE and Retro EMBRACE studies have shown that excellent local control and pelvic control could be achieved with concurrent chemoradiation and MRI-based brachytherapy in carcinoma cervix. Para-aortic nodal failure rates are higher in pelvic node-positive cases as compared to pelvic node-negative cases as demonstrated in EMBRACE studies. The current study aims to find out the benefit of adding prophylactic para-aortic node irradiation in patients of carcinoma cervix who have involved pelvic nodes on volumetric imaging. This will be a two-arm, parallel group, phase II/III open-label multicenter randomized controlled trial. Patients will be enrolled in a phase II trial where the primary endpoint will be demonstration of reduction in the risk of para-aortic recurrence. If the primary endpoint is met, a phase III trial will be initiated using the same trial design and intervention. Patients in arm A (control arm) will receive pelvic radiotherapy covering the common iliac nodes with Intensity Modulated Radiotherapy (IMRT) to a dose of 45 Gy/25 fractions over 5 weeks. Radiologically involved lymph nodes will be boosted to a dose of 55 Gy/25 fractions with simultaneous integrated boost (SIB). Patients in arm B (Experimental arm) will receive pelvic and elective para-aortic radiotherapy up to the lower border of the renal vein (IMRT) to dose of 45 Gy/25 fractions over 5 weeks. Radiologically involved lymph nodes will be boosted to a dose of 55 Gy/25 fractions with simultaneous integrated boost (SIB). Concurrent chemotherapy with cisplatin 40 mg/m This trial will demonstrate the efficacy of prophylactic para-aortic radiation in pelvic node-positive carcinoma cervix. It also gives an opportunity to standardize and assess the quality-assurance radiotherapy practices in carcinoma cervix across multiple premier institutes of the nation at the same time. Clinical Trial Registry of India (CTRI): CTRI/2023/08/057075. Registered on 30th August 2023.

Completeness and accuracy of national cancer and death registration for outcome ascertainment in trials—an ovarian cancer exemplar

Abstract Background There is a trend to increasing use of routinely collected health data to ascertain outcome measures in trials. We report on the completeness and accuracy of national ovarian cancer and death registration in the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Methods Of the 202,638 participants, 202,632 were successfully linked and followed through national cancer and death registries of Northern Ireland, Wales and England. Women with registrations of any of 19 pre-defined ICD-10 codes suggestive of tubo-ovarian cancer or notification of ovarian/tubal/peritoneal cancer from hospital episode statistics or trial sites were identified. Copies of hospital and primary care notes were retrieved and reviewed by an independent outcomes review committee. National registration of site and cause of death as ovarian/tubal/peritoneal cancer (C56/C57/C48) obtained up to 3 months after trial censorship was compared to that assigned by outcomes review (reference standard). Results Outcome review was undertaken in 3110 women on whom notification was received between 2001 and 2014. Ovarian cancer was confirmed in 1324 of whom 1125 had a relevant cancer registration. Sensitivity and specificity of ovarian/tubal/peritoneal cancer registration were 85.0% (1125/1324; 95% CI 83.7–86.2%) and 94.0% (1679/1786; 95% CI 93.2–94.8%), respectively. Of 2041 death registrations reviewed, 681 were confirmed to have a tubo-ovarian cancer of whom 605 had relevant death registration. Sensitivity and specificity were 88.8% (605/681; 95% CI 86.4–91.2%) and 96.7% (1482/1533, 95% CI 95.8–97.6%), respectively. When multiple electronic health record sources were considered, sensitivity for cancer site increased to 91.1% (1206/1324, 95% CI 89.4–92.5%) and for cause of death 94.0% (640/681, 95% CI 91.9–95.5%). Of 1232 with cancer registration, 8.7% (107/1232) were wrongly designated as ovarian/tubal/peritoneal cancers by the registry and 4.0% (47/1172) of confirmed tubo-ovarian cancers were mis-registered. In 656 with death registrations, 7.8% (51/656) were wrongly assigned as due to ovarian/tubal/peritoneal cancers while 6.2% (40/645) of confirmed tubo-ovarian cancer deaths were mis-registered. Conclusion Follow-up of trial participants for tubo-ovarian cancer using national registry data will result in incomplete ascertainment, particularly of the site due in part to the latency of registration. This can be reduced by using other routinely collected data such as hospital episode statistics. Central adjudication by experts though resource intensive adds value by improving the accuracy of diagnoses. Trial registration ISRCTN: ISRCTN22488978 . Registered on 6 April 2000

Optimizing bevacizumab dosing in first-line ovarian cancer treatment: the PGOG-ov1 trial

The management of advanced ovarian cancer has significantly developed with the integration of bevacizumab into standard therapeutic regimens. While the efficacy of bevacizumab has been established in trials such as GOG218, ICON7, and PAOLA-1, there remains a gap in understanding the advantages of the 7.5 mg/kg dose over the 15 mg/kg regimen. This study addresses this gap by evaluating the efficacy, safety, and cost effectiveness of these two dosing strategies, considering the heterogeneity of patient profiles, including BRCA mutation status and homologous recombination deficiency (HRD). This multicenter, randomized clinical trial will recruit patients with newly diagnosed, advanced-stage (FIGO III/IV) ovarian, fallopian tube, or primary peritoneal cancer. Participants will undergo three cycles of neoadjuvant chemotherapy with bevacizumab, followed by interval debulking surgery and randomization into four treatment arms stratified by BRCA and HRD status. Patients will receive either 7.5 mg/kg or 15 mg/kg bevacizumab in combination with chemotherapy during the adjuvant treatment phase and continue with maintenance therapy for up to 64 weeks, with or without the addition of olaparib. The primary endpoint is progression-free survival. The secondary endpoints include the overall response rate, quality of life, and safety profile. Data analysis focuses on subgroup evaluation of the influence of BRCA and HRD status on treatment outcomes. This study is expected to provide critical insights into optimizing bevacizumab dosing, potentially enabling the inclusion of cost-effective and safer treatment protocols without compromising efficacy. TRIAL REGISTRATION: EUCT number: 2023-509659-15-00. Registered on 09.07.2024.

HOPPSA update: changes in the study protocol of Hysterectomy and OPPortunistic SAlpingectomy, a registry-based randomized controlled trial

Abstract Background The HOPPSA trial is a multi-center national registry-based randomized controlled trial to test the safety and effectiveness of performing opportunistic salpingectomy at hysterectomy to reduce the risk of epithelial ovarian cancer (EOC). The study protocol was first published in January 2019 and is available at https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-018-3083-8. Here, we report amendments made to the study protocol since commencement of the trial. Changes in methods and analysis The primary outcomes analyses have been changed. (1) Complications will be analyzed using binomial generalized estimating equation (GEE) with log link function, while the unadjusted analyses according to Miettinen and Nurminen will be performed as a sensitivity analysis. (2) Absolute change in Menopause Rating Scale (MRS) will primarily be analyzed using a mixed effects model, adjusted for baseline MRS and center as a random effect. (3) Time to EOC will be analyzed using the mixed effects Cox regression model with center as random effect, while the unadjusted log-rank test will be performed as a sensitivity analysis. The primary outcome Complications will be based solely on the specific assessment in the GynOp quality registry. The Clavien-Dindo classification will be evaluated as a secondary outcome. Furthermore, MRS is also measured three years postoperatively to better pinpoint the onset of menopausal symptoms. Discussion The changes to the protocol mainly concern the analyses of data. No changes to recruitment, randomization, intervention, or follow-up of primary outcomes have been made. An interim analysis during 2021 concluded that the study should continue until the target sample size is reached. Trial registration ClinicalTrials.gov, NCT03045965. Registered 8 February 2017.

A multicenter noninferior randomized controlled study comparing the efficacy of laparoscopic versus abdominal radical hysterectomy for cervical cancer (stage IB3 and IIA2): study protocol of the LAUNCH 3 trial

Abstract Background Cervical cancer is and will remain to be an important health problem in China, especially with an increasing proportion of younger patients who has more specific needs. In China, surgery to remove tumor burden followed by postoperative treatment with radiotherapy and chemotherapy based on clinicopathologic factors may be the best choice for stages IB3 and IIA2 patients. Radical hysterectomy in cervical cancer has been a classic landmark surgery in gynecology. The current trial is designed to evaluate whether there is a difference between laparoscopic RH and abdominal RH in cervical cancer (stages IB3 and IIA2) patient survival under stringent operation standards and consistent surgical oncologic principles. This paper reports the rationale, design, and implementation of the trial. Methods/design This is an investigator-initiated, prospective, randomized, open, blinded endpoint (PROBE) controlled trial. A total of 1104 patients with stage IB3 and IIA2 cervical cancer will be enrolled over a period of 3 years. Patients are randomized (1:1) to either the laparoscopic RH or the abdominal RH group. Patients will then be followed up for at least 5 years. The primary end point will be 5-year overall survival, and secondary endpoints include 5-year progression-free survival, recurrence, and quality of life measurements. Discussion The study results will provide more convincing evidence-based information for stages IB3 and IIA2 cervical cancer patients and their gynecologic cancer surgeons in their choice of surgical method. Trial registration ClinicalTrials.gov, NCT04939831, retrospectively registered on 25 June 2021.

The prevention of rectovaginal fistula after rectal cancer surgery by packing with laparoscopic dislocated fat flap containing ovarian vascular pedicle anterior to the anastomotic stoma: a parallel group randomized controlled trial protocol

Abstract Background Rectovaginal fistula (RVF) is an abnormal channel formed by epithelial tissue between the anterior wall of the rectum and the posterior wall of the vagina, which manifests as vaginal gassing and defecation. It is one of the common complications of female pelvic surgeries. With the increased number of proctectomies for rectal cancer, the number of postoperative rectovaginal fistulas also increases. Once RVF occurs, the failure rate is still high with various treatments available. RVF causes great suffering to women and is still a major problem in treatment. Therefore, it is significant for female rectal cancer patients to prevent RVF after rectal cancer surgery. In this study, we introduce a new method to prevent RVF during rectal cancer radical operation. Methods In this randomized controlled trial (RCT), all operations are performed according to the principle of total mesorectal excision (TME) radical resection in rectal cancer surgery. All eligible participants will be divided into two groups: the experimental group and the control group. Experimental group: the anterior rectal wall of about 1 cm distal to the anastomosis was dislocated. Before the anastomosis of the rectal end, a fat flap (usually left side) containing the ovarian vascular pedicle was dislocated, measured by 10–15 cm in length and 2 cm in width. The fat flap containing the ovarian vascular pedicle was packed and fixed anterior to the anastomotic stoma with fibrin glue. Control group: surgery will be carried out in accordance with the TME principle. Participants will be compared on several variables, including the incidence of RVF after operation (primary outcomes), the occurrence time of postoperative RVF, the occurrence time of RVF after stoma closure, and other postoperative complications, such as anastomotic leakage, chylous leakage, and intestinal obstruction (secondary outcomes). The follow-up data collection will be conducted according to the follow-up time point, and the baseline data will also be collected for follow-up analysis. By comparing the incidence of rectovaginal leakage between the experimental group and the control group, we aim to explore the feasibility of this method for the prevention of postoperative RVF. Discussion This RCT will explore the feasibility of packing with a laparoscopic dislocated fat flap containing an ovarian vascular pedicle anterior to the anastomotic stoma after rectal cancer surgery to prevent RVF. Trial registration Chinese Clinical Trial Registry (ChiCTR) registration ChiCTR2000031449. Registered on June 26, 2019. All items of the WHO Trial registration data set can be found within the protocol.

Comparing niraparib versus platinum-taxane doublet chemotherapy as neoadjuvant treatment in patients with newly diagnosed homologous recombination–deficient stage III/IV ovarian cancer: study protocol for cohort C of the open-label, phase 2, randomized controlled multicenter OPAL trial

Abstract Background Maintenance therapy with niraparib, a poly(ADP-ribose) polymerase inhibitor, has been shown to extend progression-free survival in patients with newly diagnosed advanced ovarian cancer who responded to first-line platinum-based chemotherapy, regardless of biomarker status. However, there are limited data on niraparib’s efficacy and safety in the neoadjuvant setting. The objective of Cohort C of the OPAL trial (OPAL-C) is to evaluate the efficacy, safety, and tolerability of neoadjuvant niraparib treatment compared with neoadjuvant platinum-taxane doublet chemotherapy in patients with newly diagnosed stage III/IV ovarian cancer with confirmed homologous recombination–deficient tumors. Methods OPAL is an ongoing global, multicenter, randomized, open-label, phase 2 trial. In OPAL-C, patients will be randomized 1:1 to receive three 21-day cycles of either neoadjuvant niraparib or platinum-taxane doublet neoadjuvant chemotherapy per standard of care. Patients with a complete or partial response per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) will then undergo interval debulking surgery; patients with stable disease may proceed to interval debulking surgery or alternative therapy at the investigator’s discretion. Patients with disease progression will exit the study treatment and proceed to alternative therapy at the investigator’s discretion. After interval debulking surgery, all patients will receive up to three 21-day cycles of platinum-taxane doublet chemotherapy followed by niraparib maintenance therapy for up to 36 months. Adult patients with newly diagnosed stage III/IV ovarian cancer eligible to receive neoadjuvant platinum-taxane doublet chemotherapy followed by interval debulking surgery may be enrolled. Patients must have tumors that are homologous recombination–deficient. The primary endpoint is the pre–interval debulking surgery unconfirmed overall response rate, defined as the investigator-assessed percentage of patients with unconfirmed complete or partial response on study treatment before interval debulking surgery per RECIST v1.1. Discussion OPAL-C explores the use of niraparib in the neoadjuvant setting as an alternative to neoadjuvant platinum-taxane doublet chemotherapy to improve postsurgical residual disease outcomes for patients with ovarian cancer with homologous recombination–deficient tumors. Positive findings from this approach could significantly impact preoperative ovarian cancer therapy, particularly for patients who are ineligible for primary debulking surgery. Trial registration ClinicalTrials.gov NCT03574779. Registered on February 28, 2022.

Effectiveness of educational intervention on cervical cancer screening knowledge, attitude, and practice among Yemeni immigrant women in Klang Valley, Malaysia: a randomized controlled trial

Abstract Background Cervical cancer is one of the leading causes of cancer-related deaths worldwide. Despite the fact that several studies have looked at the topic among women in various countries, few studies have attempted to address the significance of cervical cancer screening among immigrant women. This study aims to develop and evaluate the effectiveness of an educational intervention on knowledge, attitude, and practice of cervical screening among Yemeni immigrant women in Klang Valley, Malaysia. The intervention was guided by the Health Belief Model. Methods One hundred and ten Yemeni immigrant women participated in a randomized controlled trial in Klang Valley, Malaysia. The participants were randomly assigned to either the intervention group or the control group. An online health education program on cervical cancer and cervical screening was given to the intervention group participants. Data was gathered at the baseline, immediately after the intervention, and then again 3 months later. Generalized estimating equations (GEE) were used to analyze the data using IBM SPSS software 25.0 in order to evaluate the differential changes over time. Results The results of the study show that there was a significant improvement in cervical cancer screening practice between the intervention (51%) and control groups (9%). In addition, there was a significant improvement in the mean scores of knowledge (0.04 to 0.628), perceived susceptibility (2.82 to 3.652), perceived seriousness (3.02 to 3.650), perceived benefits (2.5 to 3.777), health motivation (2.98 to 3.609) after the intervention compared with the scores before the intervention. Besides, there has been a significant decrease in the barriers to screening (3.6 to 2.795). Conclusions Online educational intervention was effective in improving women’s knowledge, attitudes, and practices regarding cervical cancer and its screening. Trial registration This trial is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR) number ACTRN12622001445763 on 11/11/2022.

The effectiveness of relugolix compared with leuprorelin for preoperative therapy before laparoscopic myomectomy in premenopausal women, diagnosed with uterine fibroids: protocol for a randomized controlled study (MyLacR study)

Abstract Background The oral gonadotropin-releasing hormone antagonist relugolix, which temporarily stops menstruation, is used to treat heavy menstrual bleeding, pelvic pressure, and low back pain in women with uterine fibroids. Treatment can also help women recover from low hemoglobin levels and possibly shrink the fibroids. However, evidence of preoperative use of relugolix before laparoscopic myomectomy is limited. Nevertheless, the treatment could reduce interoperative blood loss, decrease the risk of developing postoperative anemia, and shorten the operative time. Thus, we aim to test whether 12-week preoperative treatment with relugolix (40 mg orally, once daily) is similar to or not worse than leuprorelin (one injection every 4 weeks) to reduce intraoperative blood loss. Methods Efficacy and safety of preoperative administration of drugs will be studied in a multi-center, randomized, open-label, parallel-group, noninferiority trial enrolling premenopausal women ≥ 20 years of age, diagnosed with uterine fibroids and scheduled for laparoscopic myomectomy. Participants (n = 80) will be recruited in the clinical setting of participating institutions. The minimization method (predefined factors: presence or absence of fibroids ≥ 9 cm and the International Federation of Gynecology and Obstetrics [FIGO] type 1–5 fibroids) with randomization is used in a 1:1 allocation. Relugolix is a 40-mg oral tablet taken once a day before a meal, for 12 weeks, up to the day before surgery. Leuprorelin is a 1.88 mg, or 3.75 mg subcutaneous injection, given in three 4-week intervals during patient visits before the surgery. For the primary outcome measure of intraoperative bleeding, the blood flow is collected from the body cavity, surgical sponges, and collection bag and measured in milliliters. Secondary outcome measures are hemoglobin levels, myoma size, other surgical outcomes, and quality-of-life questionnaire responses (Kupperman Konenki Shogai Index and Uterine Fibroid Symptoms—Quality of Life). Discussion Real-world evidence will be collected in a clinical setting to use pre-treatment with an oral gonadotropin-releasing hormone antagonist to reduce intraoperative bleeding in women who undergo laparoscopic myomectomy. Trial registration jRCTs031210564 was registered on 19 January 2022 in the Japan Registry of Clinical Trials (https://jrct.niph.go.jp).

A phase III randomized clinical trial comparing laparoscopic radical hysterectomy based on open state with abdominal radical hysterectomy in patients with early-stage cervical cancer

Abstract Background Cervical cancer is the fourth most frequently diagnosed cancer and the fourth leading cause of cancer death in women, The standard treatment recommendation for women with early cervical cancer is radical hysterectomy with pelvic lymph node dissection, however, articles published in recent years have concluded that the treatment outcome of laparoscopic surgery for cervical cancer is inferior to that of open surgery. Thus, we choose a surgically new approach; the laparoscopic cervical cancer surgery in the open state is compared with the traditional open cervical cancer surgery, and we hope that patients can still have a good tumor outcome and survival outcome. This trial will investigate the effectiveness of laparoscopic cervical cancer surgery in the open-state treatment of early-stage cervical cancer. Method and design This will be an open-label, 2-armed, randomized, phase-III single-center trial of comparing laparoscopic radical hysterectomy based on open state with abdominal radical hysterectomy in patients with early-stage cervical cancer. A total of 740 participants will be randomly assigned into 2 treatment arms in a 1:1 ratio. Clinical, laboratory, ultrasound, and radiology data will be collected at baseline, and then at the study assessments and procedures performed at baseline and 1 week, 6 weeks, and 3 months, and follow-up visits begin at 3 months following surgery and continue every 3 months thereafter for the first 2 years and every 6 months until year 4.5. The primary aim is the rate of disease-free survival at 4.5 years. The secondary aims include treatment-related morbidity, costs and cost-effectiveness, patterns of recurrence, quality of life, pelvic floor function, and overall survival. Conclusions This prospective trial aims to show the equivalence of the laparoscopic cervical cancer surgery in the open state versus the transabdominal radical hysterectomy approach for patients with early-stage cervical cancer following a 2-phase protocol. Trial registration ChiCTR2300075118. Registered on August 25, 2023.

Increasing uptake of evidence-based screening services though a community health worker-delivered multimodality program: study protocol for a randomized pragmatic trial

Abstract Background Underserved ethnic minority populations experience significant disparities in HIV, hepatitis C virus (HCV), colorectal cancer (CRC), and cervical cancer incidence and mortality. Much of the excess burden of these diseases among underserved communities is due to lack of preventive care, including screening. Barriers to disease screening include low awareness, lack of access to care and health insurance, and cultural beliefs regarding disease prevention. Our current trial aims to examine community health worker (CHW)-delivered, home-based multi-modality screening for HIV, HCV, CRC, and cervical cancer simultaneously. Design We are conducting a randomized pragmatic trial among 900 Haitian, Hispanic, and African-American participants from diverse underserved communities in South Florida. People between the ages of 50 and 65 who have not had appropriate HIV, HCV, CRC, and cervical cancer screening per United States Preventive Services Task Force (USPSTF) recommendations are eligible for the study. Participants are recruited by CHWs and complete a structured interview to assess multilevel determinants of disease risk. Participants are then randomized to receive HIV, HCV, CRC, and cervical cancer screening via navigation to care by a CHW (Group 1) or via CHW-delivered home-based screening (Group 2). The primary outcome is completion of screening for each of these diseases within 6 months post-enrollment. Discussion Our trial is among the first to examine the effectiveness of a CHW-delivered, multimodality, home-based disease-screening approach. If found to be effective, this approach may represent a cost-effective strategy for disease screening within underserved and underscreened minority groups. Trial registration Clinical Trials.gov # NCT02970136, registered November 21, 2016.

Comparison of outcomes and side effects for neoadjuvant chemotherapy with weekly cisplatin and paclitaxel followed by chemoradiation vs. chemoradiation alone in stage IIB–IVA cervical cancer: study protocol for a randomized controlled trial

Abstract Background Currently, the standard treatment for locally advanced cervical cancer is concurrent chemoradiation (CCRT). The effect of neoadjuvant chemotherapy in advanced cervical cancer is controversial. Studies have shown that the addition of a weekly regimen of neoadjuvant chemotherapy (NACT) followed by CCRT may be superior to a thrice-weekly regimen of NACT and CCRT. Among patients who had not received prior cisplatin, a cisplatin and paclitaxel (TP) regimen resulted in longer overall survival than other regimens. This study aims to investigate the feasibility, safety, and efficacy of NACT with weekly TP followed by CCRT. Methods This is a prospective, randomized, open-labeled, multicentered phase III study. Based on a 65% of 2-year disease-free survival (DFS) rate in the CCRT group and 80% of that in NACT followed by CCRT group, and on prerequisite conditions including an 8% loss to follow-up, a two-sided 5% of type I error probability, and an 80% of power, a total of 300 cases were required for enrollment. Patients with IIB–IVA cervical cancer will be randomly allocated in a 1:1 ratio to one of two intervention arms. In the study arm, patients will receive dose-dense cisplatin (40 mg/m2) and paclitaxel (60 mg/m2) weekly for 4 cycles followed by CCRT (45 Gy in 5 weeks concurrent with cisplatin 40 mg/m2 weekly) plus image-guided adaptive brachytherapy (IGBRT). In the control arm, patients will undergo CCRT treatment. The primary endpoint of the study is 2-year disease-free survival (DFS); the secondary endpoints are 5-year overall survival (OS) and disease-free survival (DFS), the response rate 3 months after treatment completion, grade III/IV adverse effects, and quality of life, and potential biomarkers for predicting treatment response will also be studied. Discussion The data gathered from the study will be used to determine whether NACT with weekly TP followed by CCRT may become an optimized treatment for locally advanced cervical cancer. Trial registration Chinese Clinical Trial Registry ChiCTR1900025327. Registered on 24 August 2019. medresman.org.cn ChiCTR1900025326

dVP_FAM—development and evaluation of a transsectoral digital care platform for individuals with familial cancer risks: study protocol for a multi-centre, cluster-randomised, mixed-methods study

Abstract Background Individuals with a family history of cancer face an increased risk of developing breast and ovarian cancer. Up to 30% of the 70,000 annual breast cancer cases in Germany are associated with a familial cancer burden. Early identification of these risks is crucial as personalised measures can enable early detection or prevention of cancer. Primary care gynaecologists are uniquely suited to assess family histories and facilitate referrals to hereditary cancer centres. However, solutions on how to support early referral are still lacking. This study evaluates the impact of the digital care platform dVP_FAM as a potential remedy compared to standard care. The primary hypothesis is that the platform will increase the proportion of care-seeking women with a familial cancer risk who have not yet developed cancer. Secondary outcomes include improvements in care efficiency, patient empowerment, and health-related quality of life. Methods The study is a multi-centre, cluster-randomised, mixed-method trial involving 44 gynaecological centres and 800 participants recruited through hereditary breast and ovarian cancer centres. All participants receive standard guideline-based care, while the intervention group also uses the dVP_FAM platform. The primary endpoint measures the proportion of participants with a familial cancer history who are cancer-free when seeking specialist counselling. Secondary outcomes are assessed using validated tools like the SF-12 and custom measures. Data collection employs a convergent mixed-methods approach, integrating quantitative and qualitative evidence. Discussion The dVP_FAM platform represents an innovative approach to digitising cancer prevention in Germany, enhancing early detection and care coordination. If successful, dVP_FAM could serve as a scalable model for digital health innovations, improving efficiency and modernising the delivery of personalised care across health systems. Trial registration German Clinical Trials Register, DRKS00030371. Registered on 02 October 2023.

GnRH-a-based fertility-sparing treatment of atypical endometrial hyperplasia (AEH) and early endometrial carcinoma (EC) patients: a multicenter, open-label, randomized designed clinical trial protocol

Around 4% of women receive an endometrial cancer diagnosis before turning 40, mainly those without prior childbirth experience and a strong desire to preserve their ability to conceive. Consequently, for young patients diagnosed with atypical endometrial hyperplasia (AEH) or early endometrial carcinoma (EC), a fertility-preserving approach employing high-dose oral progesterone has been adopted. However, previous research has shown a notable relapse rate. Furthermore, the extended use of substantial oral progesterone doses may hinder ovarian function and raise the risk of weight gain, liver issues, blood clotting, and breast cancer. We previously assessed the clinical effectiveness and pregnancy outcomes of gonadotropin-releasing hormone agonist (GnRH-a) based re-treatment for women with EC and AEH who did not respond to oral progestin therapy but achieved favorable treatment results and reproductive outcomes. This study will be an open-label, two-armed, randomized, investigator-initiated multicenter trial evaluating the combination of GnRH-a with the levonorgestrel-releasing intrauterine system or the combination of GnRH-a with an aromatase inhibitor (comprising a subcutaneous GnRH-a injection every 4 weeks and daily oral letrozole 2.5 mg). A total of 226 participants will be randomly allocated to one of the two treatment groups in a 1:1 ratio. The primary objective is to determine the effectiveness of GnRH-a-based re-treatment in achieving a complete response (CR) at 24 weeks for patients with AEH or EC. Secondary objectives include assessing the pregnancy rate 12 weeks after treatment, as well as post-treatment pregnancy outcomes and the rate of recurrence. The protocol received approval from the Institutional Review Board of Peking Union Medical College Hospital and from boards at five other institutions. The trial will adhere to the principles outlined in the World Medical Association's Declaration of Helsinki and follow Good Clinical Practice standards. The trial results will be disseminated through publication in a peer-reviewed journal. Prospective evidence supporting conservative treatment for EC and AEH is limited. There is a need for new approaches that can achieve higher CR rates with fewer side effects. This trial will assess the effectiveness of GnRH-a-based fertility-sparing treatment in obese women and recurrent patients, offering a promising alternative for patients with EC and AEH. Chinese Clinical Trial Registry ChiCTR2200067099. Registered on December 27, 2022.

The clinical trial of alternative relugolix administration for uterine leiomyoma prior to surgically treatment: a study protocol for Non-Adverse Relugolix Administration (NARA) trial

Abstract Background Uterine leiomyomas are common for reproductive-aged women and affect women’s quality of life due to heavy menstrual bleeding or dysmenorrhea. Leiomyomas grow according to estradiol exposure and decrease after post-menopause. In case serious symptoms are caused by leiomyomas, pharmacotherapy or surgical treatment is proposed. Prior to surgical treatment, pharmacotherapies aimed at the reduction of leiomyoma and uterine volume or improvement of anemia are introduced to conduct minimum invasive surgery (i.e., to reduce blood loss or surgical duration). Recently, relugolix (40 mg orally once daily) as a gonadotropin-releasing hormone (GnRH) receptor antagonist has proved its sufficient efficacy in suppressing estradiol levels without the transient estradiol flare-up compared with GnRH agonist. However, long-term administration should not be permitted liable to for climacteric disorder or osteoporosis, and evidence is lacking on the actual efficacy and extent of adverse effects of the every-other-day dosing regimen. This trial aimed to prove non-inferiority in volume reduction effect on leiomyoma and safety (i.e., reduction of adverse effects) by every-other-day administration after 2 months of everyday administration compared to daily administration throughout the duration. Methods A minimization adaptive randomized control trial (RCT) will be conducted. Patients (over 20 years old) harboring leiomyoma who will be undergoing surgical treatment will be invited to participate. Patients who are enrolled in the intervention group will receive every-other-day administration for 16 weeks after 8 weeks of daily administration. Patients who are enrolled in the control group will receive daily throughout the 24 weeks. The primary outcome is the leiomyoma volume reduction, and the secondary endpoints are the reduction of uterine volume, the occurrence of the climacteric disorder, genital bleeding days, change rate of serum hormone or bone turnover markers, and bone mineral density after 24 weeks compared to before administration. Discussion This study aims to prove both the non-inferiority in leiomyoma volume reduction and superiority in adverse effects occurrence reduction, which will provide a novel method to escape adverse effects while maintaining the effect of leiomyoma reduction. Trial registration Japan Registry of Clinical Trials jRCTs051230078. Registered on 26 July 2023.

Attitudes and barriers to participation in window-of-opportunity trials reported by White and Asian/Asian British ethnicity patients who have undergone treatment for endometrial cancer

Abstract Purpose Window-of-opportunity trials (WOT) are a study design that have been used to investigate drug activity in endometrial cancer (EC). Recruitment to cancer clinical trials by patients from ethnic minority groups is reported to be lower than for patients of White ethnicity. Methods A verbal questionnaire was conducted with White and Asian/Asian British ethnicity patients who had undergone treatment for EC. Strategic purposeful sampling was used to recruit patients from diverse social/educational backgrounds. Questions explored: background knowledge of clinical research, WOT study design, and views on medications that might be investigated. Thematic analysis was used to explore motivations for WOT participation and perceived barriers. Results In total, 21 patients were recruited to the study (15 White and 6 Asian/Asian British). Views on optimum time to receive trial information differed, preferences ranging from 'at the time of diagnosis' to 'a few days after diagnosis'. The choice of medication under investigation had a strong influence on potential willingness to participate, with greater interest reported in medications derived from vitamins or food supplements rather than hormone-based drugs. Potential barriers to participation included concern over potential side-effects and the emotional/physical burden of a cancer diagnosis prior to major surgery. Discussion This study provides important insights into patients’ views on WOT participation in EC and raises issues that need to be considered for future trial design and participant recruitment materials. The timing and format of study information and type of substance under investigation were factors influencing potential participation. Future studies should consider using multi-lingual visual information videos to address information needs, as this may encourage participation by ethnic minority patients.

Minimally invasive versus open radical trachelectomy for early-stage cervical cancer: protocol for a multicenter randomized controlled trial in China

Abstract Background There are limited data comparing the oncologic and fertility outcomes of patients with early-stage cervical cancer (CC) treated by minimally invasive radical trachelectomy (MIRT) or abdominal radical trachelectomy (ART). The purpose of this multicenter study is to compare the oncologic and fertility outcomes of patients treated by MIRT or ART in a randomized controlled manner in China. Methods This is a noninferiority, randomized controlled trial performed at 28 Chinese centers; the study is designed to compare the oncologic and fertility outcomes of patients treated by MIRT (robot-assisted or laparoscopic RT) or ART. Patients will be recruited if they have been diagnosed with stage IA1 (with lymphovascular space invasion), IA2, or IB1 CC (with a maximum tumor diameter ≤ 2 cm) in the FIGO 2009 staging system and histological subtypes of squamous carcinoma, adenocarcinoma, or adenosquamous carcinoma and if they are also aged 18 to 40 years. These candidates will be randomly assigned to undergo MIRT or ART. The primary endpoint will be disease-free survival. Secondary endpoints will consist of overall and disease-free survival rates, fertility outcomes, and quality of life. A total of 414 patients are needed to accomplish the study goal, with 90.1% power at a 0.050 significance level to detect an equivalence hazard ratio of 0.75 in the ART group, considering 20% loss to follow-up. Discussion The results of the trial should provide robust evidence to surgeons regarding options for the surgical approach in patients with early-stage CC who have a strong willingness to preserve fertility. Trial registration ClinicalTrials.gov NCT03739944. Registered on November 14, 2018

UKCTOCS update: applying insights of delayed effects in cancer screening trials to the long-term follow-up mortality analysis

Abstract Background During trials that span decades, new evidence including progress in statistical methodology, may require revision of original assumptions. An example is the continued use of a constant-effect approach to analyse the mortality reduction which is often delayed in cancer-screening trials. The latter led us to re-examine our approach for the upcoming primary mortality analysis (2020) of long-term follow-up of the United Kingdom Collaborative Trial of Ovarian Cancer Screening (LTFU UKCTOCS), having initially (2014) used the proportional hazards (PH) Cox model. Methods We wrote to 12 experts in statistics/epidemiology/screening trials, setting out current evidence, the importance of pre-specification, our previous mortality analysis (2014) and three possible choices for the follow-up analysis (2020) of the mortality outcome: (A) all data (2001–2020) using the Cox model (2014), (B) new data (2015–2020) only and (C) all data (2001–2020) using a test that allows for delayed effects. Results Of 11 respondents, eight supported changing the 2014 approach to allow for a potential delayed effect (option C), suggesting various tests while three favoured retaining the Cox model (option A). Consequently, we opted for the Versatile test introduced in 2016 which maintains good power for early, constant or delayed effects. We retained the Royston-Parmar model to estimate absolute differences in disease-specific mortality at 5, 10, 15 and 18 years. Conclusions The decision to alter the follow-up analysis for the primary outcome on the basis of new evidence and using new statistical methodology for long-term follow-up is novel and has implications beyond UKCTOCS. There is an urgent need for consensus building on how best to design, test, estimate and report mortality outcomes from long-term randomised cancer screening trials. Trial registration ISRCTN22488978 . Registered on 6 April 2000.

DICE: Dual mTorc Inhibition in advanCed/recurrent Epithelial ovarian cancer resistant to standard treatment—a study protocol for a randomised trial investigating a novel therapy called TAK228

Abstract Background The standard initial treatment for ovarian cancer is surgery and platinum-based chemotherapy and potentially maintenance therapy with avastin or inhibitors of poly-ADP ribose polymerase (PARP). While a proportion of women are cured by this approach, the vast majority will relapse and become resistant to platinum chemotherapy either initially or on subsequent treatment. There is an unmet need to improve response to treatment and quality of life in these women. TAK228 is a novel therapy that can be added to standard treatment in the participant population and the aim of the DICE trial is to assess its effectiveness. Laboratory and clinical research has shown that these ovarian cancers may respond to the molecular target of a drug such as TAK228, and there have been studies using it in other advanced solid tumours including endometrial cancer. Methods One hundred twenty-four eligible women will be recruited from participating research sites in the United Kingdom (UK) and Germany. Randomised participants will receive either weekly paclitaxel alone (standard treatment, n = 62) or TAK228 plus weekly paclitaxel (n = 62) until the cancer significantly worsens; there are significant adverse events or any other protocol-defined stopping criteria. Participants will be monitored for response to treatment (using radiological imaging), adverse events and quality of life during both randomised treatment and subsequent follow-up. Discussion The primary objective/endpoint of the study is to compare the two treatments in terms of progression-free survival, or the length of time that each participant is alive without the cancer significantly worsening according to defined assessment criteria. If the addition of TAK228 to weekly paclitaxel chemotherapy is shown to significantly improve this statistically, and adverse events and quality of life are not significantly worse than standard treatment, then TAK228 plus weekly paclitaxel could potentially be taken forward within the context of a larger phase III trial. Trial registration ClinicalTrials.govNCT03648489. Registered on 27 August 2018.

Evaluation of two evidence-based decision aids for female BRCA1/2 mutation carriers in Germany: study protocol for a randomised controlled parallel-group trial

Abstract Background Women with BRCA1/2 mutations have a higher risk of developing breast and ovarian cancer compared to women of the general population. Various preventive options are available to deal with the increased risk of developing cancer. These include intensified breast cancer screening and risk-reducing bilateral mastectomy and salpingo-oophorectomy. The choice of a preventive option can lead to increased decisional conflict. To support these women in their decision-making process, two evidence-based decision aids were developed in an upstream research process and adapted to the German healthcare context. These will be evaluated within a randomised controlled trial (RCT) in terms of their effects on decision-making, women’s level of information and psychological outcome variables. Methods A sample of 310 women carrying BRCA1/2 mutations (A) without a history of cancer or (B) with a history of unilateral breast cancer who have received post-test genetic counselling will be enrolled. Upon study consent, women will be randomly assigned to either the intervention or the control group. All participants will receive standard care including a physician’s letter summarising the counselling content. After baseline data collection (t0), the intervention group receives the respective decision aid while the control group receives standard care only. The primary outcome variable assessed at a 3-month follow-up (t1) is the change of extent in decisional conflict (measured with the Decisional Conflict Scale). Secondary outcome variables comprise the stage of decision-making, self-reported symptoms of anxiety, depression and stress due to the genetic test result, and knowledge regarding cancer risks and preventive options. At t1, the extent of preparation for decision-making and acceptability of the decision aids will also be examined. Another secondary outcome variable assessed at 6-month follow-up (t2) is the extent of decision regret. Discussion These will be the first decision aids available for BRCA1/2 mutation carriers in Germany to be evaluated regarding their effectiveness and acceptability in clinical use within an RCT. Subsequently, they are to be integrated into the care concept of the centres of the German Consortium for Hereditary Breast and Ovarian Cancer and the affiliated breast centres. Trial registration {2a} DRKS DRKS00015823. Retrospectively registered on 14 June 2019

Statistical analysis plan for the Dual mTorc Inhibition in advanCed/recurrent Epithelial ovarian, fallopian tube or primary peritoneal cancer (of clear cell, endometrioid and high-grade serous type, and carcinosarcoma) trial (DICE)

Abstract Background Treatment for ovarian cancer includes platinum-based chemotherapy, but many women become resistant to chemotherapy, becoming platinum-resistant. Standard of care for these women is weekly paclitaxel chemotherapy, but cancers can often become paclitaxel resistant. TAK228, an investigational dual TORC1/2 inhibitor, is an oral therapy that can be added to standard treatment. The DICE trial is a phase II international multicentre, parallel-group, superiority clinical trial with 1:1, open label randomisation which has the aim of investigating the effectiveness of TAK228 plus weekly paclitaxel. The planned sample size is 124 women (62 per treatment arm) with platinum-resistant ovarian cancer. Objective To outline the planned analyses for DICE in a statistical analysis plan (SAP) before database hard lock and the start of analysis. This ensures that bias is minimised during the analysis phase. Results This SAP provides detailed descriptions of the analysis principles and statistical procedures for analysing primary and secondary outcomes of the trial. The primary outcome is overall progression-free survival (PFS). Secondary outcomes include progression-free survival (PFS) at 24 weeks, overall response rate (ORR), duration of response (DoR), time to progression (TTP), clinical benefit rate (CBR) at 4 months, Cancer Antigen 125 (CA125) response according to Gynaecological Cancer Intergroup (GCIG) criteria, overall survival (OS), safety and tolerability as assessed by adverse events and the quality-of-life questionnaires (EORTC QLQ-C30 and EORTC QLQ-OV28). This detailed description includes significance levels, sensitivity analyses and compliance analysis. Discussion The DICE trial will determine whether the addition of TAK228 to weekly paclitaxel chemotherapy shows a statistically significant improvement to participant’s progression free and overall survival and that the adverse events (AEs) and quality of life (QoL) are not significantly worse than the standard treatment. The study commenced recruitment in September 2018. An interim analysis was performed in early 2021, the results of which advised continuation of the trial. The study recruitment is ongoing and is due to complete by the end of 2021. Trial registration ClinicalTrials.govNCT03648489. Registered on 27 August 2018

Safety and efficacy of the new CryoPop® cryotherapy device for cervical dysplasia in low- and middle-income countries: study protocol for a multicenter open-label non-inferiority clinical trial with historical controls

Abstract Background Cervical cancer is the fourth most common cancer in the world, affecting mainly women residing in low- and middle-income countries. Progression from a pre-invasive phase to that of an invasive phase generally takes years and provides a window of opportunity to screen for and treat precancerous lesions. Methods This study is being conducted at four sites in north Karnataka, India. Community sensitization activities have been organized in the study areas to create awareness among stakeholders, including elected representatives, physicians, health care workers, and potential participants. Organized community based as well as hospital-based screening is being conducted using visual inspection with acetic acid (VIA). Screen positive women are referred to respective study hospitals for colposcopy and directed biopsy. Participants with confirmed high-grade cervical dysplasia (high-grade squamous intraepithelial lesions or HSIL) who fit all other eligibility criteria will be recruited to the study and will receive cryotherapy using CryoPop®, an innovative new cryotherapy device. Discussion There is a need to develop an inexpensive, simple, and effective cryotherapy device for use by frontline health care providers at locations where screening and timely treatment can be given, accelerating access to cervical cancer prevention services and minimizing loss to follow-up of women with precancerous lesions who need treatment. Trial registration Clinical Trial Registry - India CTRI/2019/01/017289 ClinicalTrials.Gov number NCT04154644 . Registered on November 6, 2019.

Single-dose HPV vaccination efficacy among adolescent girls and young women in Kenya (the KEN SHE Study): study protocol for a randomized controlled trial

AbstractBackgroundHPV infection is the primary cause of cervical cancer, a leading cause of cancer among women in Kenya and many sub-Saharan African countries. High coverage of HPV vaccination is a World Health Organization priority to eliminate cervical cancer globally, but vaccine supply and logistics limit widespread implementation of the current two or three dose HPV vaccine schedule.MethodsWe are conducting an individual randomized controlled trial to evaluate whether a single dose of the bivalent (HPV 16/18) or nonavalent (HPV 16/18/31/33/45/52/58/6/11) HPV vaccine prevents persistent HPV infection, a surrogate marker for precancerous lesions and cervical cancer. The primary objective is to compare the efficacy of immediate, single-dose bivalent or nonavalent vaccination with delayed HPV vaccination. Kenyan women age 15–20 years old are randomized to immediate bivalent HPV and delayed meningococcal vaccine (group 1), immediate nonavalent HPV vaccine and delayed meningococcal vaccine (group 2), or immediate meningococcal vaccine and delayed HPV vaccine (group 3) with 36 months of follow-up. The primary outcome is persistent vaccine-type HPV infection by month 18 and by month 36 for the final durability outcome. The secondary objectives include to (1) evaluate non-inferiority of antibody titers among girls and adolescents (age 9 to 14 years) from another Tanzanian study, the DoRIS Study (NCT02834637), compared to KEN SHE Study participants; (2) assess the memory B cell immune response at months 36 and 37; and (3) estimate cost-effectiveness using the trial results and health economic models.DiscussionThis study will evaluate single-dose HPV vaccine efficacy in Africa and has the potential to guide public health policy and increase HPV vaccine coverage. The secondary aims will assess generalizability of the trial results by evaluating immunobridging from younger ages, durability of the immune response, and the long-term health benefits and cost of single-dose HPV vaccine delivery.Trial registrationClinicalTrials.govNCT03675256. Registered on September 18, 2018

Community-based intervention for cervical cancer screening uptake in a semi-urban area of Pokhara Metropolitan, Nepal (COBIN-C): study protocol for a cluster-randomized controlled trial

Abstract Background Previous studies suggest that health intervention designed to increase cervical cancer screening has been effective to reduce cervical cancer incidence and mortality. The aim of this study is to determine the effect of a home-based health education intervention for increasing cervical cancer screening uptake delivered by trained female community health volunteers (FCHVs), a category of community health worker in Nepal. Methods A community-based, open-label, two-armed, cluster-randomized trial [seven clusters (geographical wards) randomized for the intervention, and seven for the control arm]. The participants are recruited from a population-based survey with a sample size of 884. Based on population proportion size, 277 women will be recruited for the intervention group and 413 women recruited for the control group. A 12-month community-based health education intervention will be administered mobilizing the FCHVs, based on the Health Belief Model. The primary outcome measure of the study will be the difference in percentage of cervical cancer screening uptake between the two study arms. The primary outcomes will be modeled by using mixed-effect logistic regression analysis. Discussion COBIN-C is the first study investigating the effect of a community-based health education intervention by FCHVs on increasing cervical cancer screening uptake among women in Nepal. The purpose of this study is to develop and implement a home-based, culturally sensitive program to increase cervical cancer screening coverage at the community level. Trial registration ClinicalTrials.gov NCT03808064 . Registered on January 14, 2019.

Impact of health education intervention on demand of women for cervical cancer screening: a cluster-randomized controlled trial

Abstract Background Cervical cancer is considered preventable disease, though it is the second largest killer of women’s cancer in low and middle-income countries. Despite the government’s attempts to broaden screening facilities, the screening service utilization was poor. Our study evaluated the impact of health education intervention on women’s demand for cervical cancer screening. Methods Community-based cluster-randomized controlled trial was conducted in thirty district towns as clusters in Tigray region, Ethiopia. A total of 700 women aged 20 to 60 years were recruited for both groups using simple random sampling from April to July, 2018. After baseline data collection, health education intervention was given to the intervention group by trained health professionals using power point presentation and peer group discussion at the nearest health institution. The health education was given for three days followed by subsequent consultations for 6 months. The outcome variable was demand of women for cervical cancer screening. The intent-to-treat and per-protocol analysis were considered to evaluate the inflation of the loss to follow-up on effect size. Chi-square test was used to assess the difference of variables between control and intervention groups at baseline data. Finally, difference in difference analysis was used to see the true effect of the intervention on outcome variable. Results A total of 674 participants (340 in intervention and 334 in control groups) were able to complete the follow-up, making a response rate of 96.3%. At baseline, the differences in proportion of all outcome variables in control and intervention groups were not statistically significant. After follow-up, a statistically significant difference between control and intervention groups was observed in the proportion of willingness to screen (p value = 0.000), having plan to screen (p value = 0.000), ever screened (p value = 0.000), and the overall demand for cervical cancer screening (p value = 0.000). Finally, the impact of intervention was explained by the difference in differences in the proportion of willingness to screen (36.6%) (p value < 0.000), having plan to screen (14.6%) (p value < 0.000), ever screened (16.9%) (p value < 0.000), and overall demand for cervical cancer screening (36.9%) (p value < 0.000). Conclusion This study revealed that health education intervention could increase in overall demand of women for cervical cancer screening. Thus, it would be helpful to consider health education in health planning and service provision. Trial registration The registration number is PACTR201808126223676; date registered: 23 April 2018, and the type is “retrospectively registered.”

Improve the cervical cancer prevention behaviors through mobile-based educational intervention based on I-CHANGE model: study protocol for a randomized controlled trial

AbstractBackgroundApplications of mobile technologies (mHealth) have the potential to reduce health inequalities, give patients more control over their health, and improve health care’s cost-effectiveness. The widespread use of mobile phones offers us a new way to prevent cervical cancer. The objective of the study was to design and develop a mobile phone application (app) that aims to conduct a behavioral intervention for women and to evaluate the efficacy of the app-based intervention.MethodsThis study involves 5 phases. In the first phase, understanding women’s perspectives will be identified using a qualitative approach based on the I-Change model. In phase 2, the results from the qualitative approach and requirement prioritization through providing experts’ perspectives will be done. The main outputs of this phase will be resulted in prioritizing the main measurable effective variables of the I-Change model. Phase 3 will be processed for the development and psychometric of an assessment tool regarding selected constructs. In phase 4, the App framework and content development will be performed. In phase 5, a three-armed, parallel-design randomized controlled trial will be conducted on women. Two hundred ten women will be randomly assigned to three groups including two intervention groups and one control group. The intervention groups included the following: (1) a mobile application and (2) a digital book. The data will be evaluated using tools designed and constructed in phase 3 of the study at baseline in 3-month follow-up assessments. The impact of the two interventions on cervical cancer prevention behaviors through mobile-based educational intervention will then be evaluated.DiscussionA theory-based health education program using a mobile app to improve cervical cancer-preventive behaviors will be implemented for the first time in Iran. With an effective health mobile-based educational design, it is very important to determine whether Iranian women will be motivated to adhere to preventive behavior related to CC.Trial registrationIranian Clinical Trial Register IRCT20181205041861N3. Registered V2.0 on 26 October 2021.

A prospective trial to evaluate the clinical efficacy and safety of neoadjuvant chemotherapy with arsenic trioxide and carboplatin in locally advanced cervical cancer: a study protocol for randomized controlled clinical

Abstract Background Cervical cancer is the fourth most common malignancy in women, which is threatening female reproductive tract health. Chemotherapy can be used for neoadjuvant therapy of locally advanced cervical cancer and postoperative adjuvant therapy for patients with high-risk factors, so as to reduce the focus, sensitize radiotherapy, and reduce recurrence. The current first-line treatment is paclitaxel combined with platinum. Many literature studies have found that As2O3 alone or in combination with platinum drugs have good efficacy in a variety of tumors both in vivo and in vitro. Moreover, our research group has verified that the efficacy of As2O3 combined with platinum drugs in the treatment of cervical cancer is not inferior to the traditional first-line regimen at the cellular and animal levels, and paclitaxel is more expensive than As2O3. Hence, we aim to evaluate the clinical efficacy and safety of neoadjuvant chemotherapy with As2O3 and carboplatin in locally advanced cervical cancer. Methods Sixty participants in the IB2, IIA2, and IIB stages of cervical cancer will be recruited in this study. After excluding patients who did not meet the criteria, they were randomly assigned to two groups in a 1:1 ratio. All patients underwent colposcopic biopsies to confirm the diagnosis and detailed clinical examinations. Eligible patients will receive either 2 cycles of paclitaxel and carboplatin or As2O3 and carboplatin every 3 weeks. Patients were assessed for clinical efficacy after the second cycle of chemotherapy. Patients who had disease stable or disease progression at these time points will receive concurrent chemotherapy and radiation directly, while responders will receive PiverRutledge grade III radical hysterectomy and bilateral pelvic lymphadenectomy. Both groups of patients undergoing radical hysterectomy were given adjuvant therapy as per protocol-defined criteria. The efficacy and toxicity of the two groups were evaluated according to WHO acute and subacute toxicity classification standards. Discussion This is the first single-center, prospective, two-arm design, open-label randomized control trial that will evaluate the clinical efficacy and safety of neoadjuvant chemotherapy with As2O3 and carboplatin in locally advanced cervical cancer. Trial registration ChineseClinicalTrialRegistryChiCTR1900023822. Registered on 13 June 2019.

A multicenter non-inferior randomized controlled study comparing the efficacy of laparoscopic versus abdominal radical hysterectomy for cervical cancer (stages IB1, IB2, and IIA1): study protocol of the LAUNCH 2 trial

Abstract Background A retrospective study and a randomized controlled trial published in late 2018 have shown that laparoscopic radical hysterectomy (RH) was associated with worse survival than abdominal RH among patients with early-stage cervical cancer. Radical hysterectomy in cervical cancer has been a classic landmark surgery in gynecology; therefore, this conclusion is pivotal. The current trial is designed to reconfirm whether there is a difference between laparoscopic RH and abdominal RH in cervical cancer (stages IB1, IB2, and IIA1) patient survival under stringent operation standards and consistent surgical oncologic principles. Methods/design This is an investigator-initiated, Prospective, Randomized, Open, Blinded End-point (PROBE)-controlled non-inferiority trial. A total of 780 patients with stage IB1, IB2, and IIA1 cervical cancer will be enrolled over a period of 3 years. Patients are randomized (1:1) to either the laparoscopic RH or the abdominal RH group. Patients will then be followed up for at least 5 years. The primary endpoint will be 5-year progression-free survival, and secondary endpoints include 5-year overall survival, recurrence, and quality of life measurements. Discussion The debate on laparoscopic versus abdominal RH is still ongoing, and high-quality evidences are needed to guide clinical practice. The study results will provide more convincing evidence-based information for early-stage cervical cancer patients and their gynecologic cancer surgeons in their choice of surgical method. Trial registration ClinicalTrials.govNCT04929769. Registered on 18 June 2021