Surgery or Chemotherapy in Recurrent Ovarian Cancer (SOC 1 Trial)?

NCT01611766UNKNOWNPHASE3INTERVENTIONAL

Summary

Key Facts

Lead Sponsor

Shanghai Gynecologic Oncology Group

Enrollment

356

Start Date

2012-07-19

Completion Date

2019-12-01

Study Type

INTERVENTIONAL

Official Title

Evaluation of Secondary Cytoreductive Surgery in Platinum-Sensitive Recurrent Ovarian Cancer: A Phase III, Multicenter, Randomized Trial

Interventions

Secondary Cytoreductive SurgerySalvage Chemotherapy

Conditions

Ovarian Epithelial Cancer RecurrentFallopian Tube CarcinomaPrimary Peritoneal Carcinoma

Eligibility

Age Range

18 Years – 80 Years

Sex

FEMALE

Inclusion Criteria:

* Age at recurrence ≥ 18 years
* Patients with platinum-sensitive, first relapsed epithelial ovarian, primary peritoneal, or fallopian tube cancer (EOC, PPC, FTC), which is defined as those with treatment -free interval of 6 months or more.
* A complete secondary cytoreduction predicting score, iMODEL \[Tian WJ, Ann Surg Oncol 2012,19(2):597-604\]\<=4.7, including FIGO stage (0 or 0.8); residual disease after primary surgery (0 or 1.5); Progression-free interval (0 or 2.4); PS ECOG (0 or 2.4); Ca125 (0 or 1.8); and ascites at recurrence (0 or 3.0). If PI and CO-PI reach consensus that the recurrent tumor detected by PET/CT could be completely resected, the index of CA125 could be scored as 0. (Revised on 09/30/2013)
* Assessed by the experienced surgeons, complete resection of all recurrent disease is possible. If single lesion outside the peritoneal cavity can be resected, MRI/CT or PET/CT scan should be performed to exclude simultaneous intra-abdominal lesions.
* Patients who have given their signed and written informed consent and their consent.

Exclusion Criteria:

* Patients with borderline tumors as well as non-epithelial tumors.
* Patients for interval-debulking, or for second-look surgery, or palliative surgery planned.
* Impossible to assess the resectability or evaluate the score. Radiological signs suggesting complete resection is impossible.
* More than one prior chemotherapy.
* Second relapse or more
* Patients with second or other malignancies who have been treated by surgery, if the treatment might interfere with the treatment of relapsed ovarian cancer or if major impact on prognosis is expected.
* Progression during chemotherapy or recurrence within 6 months after first-line therapy
* Any contradiction not allowing surgery and/or chemotherapy

  1. Accompanied by hypoxia serious chronic obstructive pulmonary disease
  2. Uncontrolled hypertension, cerebrovascular accident/ Stroke, myocardial infarct, unstable angina, untreated thrombosis, chronic congestive heart failure, or serious arrhythmia in need of medicine.
  3. Severe hepatitis, history of liver disease, nephrotic syndrome, renal insufficiency
  4. Active ulcer history, abdominal wall fistula, perforation of gastrointestinal tract, or Intra-abdominal abscess, or simultaneously apply treatment/prevent ulcers therapy.
  5. Uncontrolled diabetes
  6. Uncontrolled epilepsy need long-term antiepileptic treatment.
* Any medication induced considerable risk of surgery, e.g. estimated bleeding due to oral anticoagulating agents, or bevacizumab.

Outcome Measures

Primary Outcomes

Overall survival

from date of randomisation until death

Time frame: Up to 60 months after last patient randomized

Progression-free survival

interval between date of randomization and the date of second relapse/ progression or death, whatever occurs first

Time frame: Up to 24 months after last patient randomized

Secondary Outcomes

Accumulating Treatment-free survival (TFSa)

the time of OS minus each treatment period after randomization, including surgery and chemotherapy

Time frame: Up to 60 months after last patient randomized

Overall survival after the adjustment of one-way treatment switching

OS adjusted by statistical models for crossover

Time frame: Up to 60 months after last patient randomized

30-day post-operative complications

MSKCC surgical complications grading method and CTCAE v4.03 criteria will be adopted for evaluating the perioperative complications

Time frame: From the operation until after 30 days

Validation of iMODEL

iMODEL score to predict complete resection

Time frame: From randomization to operation

Patient compliance

compliance with protocol

Time frame: Up to 60 months after last patient randomized

Quality of life assessments

The EORTC core quality of life questionnaire (QLQ-C30, version 3.0) Functional Assessment of Cancer Therapy- Ovary (FACT-O)

Time frame: Study entry; 6 months; 12 months; 24 months and 60 months after randomization

Time to first subsequent anticancer therapy

From date of randomization until the date of first recurrent anticancer therapy

Time frame: Up to 60 months after last patient randomized

Time to second subsequent anticancer therapy

From date of randomization until the date of secondary recurrent anticancer therapy

Time frame: Up to 60 months after last patient randomized

Locations

Sun Yat-sen University Cancer Center, Guangzhou, China

Fudan University Cancer Hospital, Shanghai, China

Shanghai Zhongshan Hospital, Shanghai, China

Zhejiang Cancer Hospital, Hangzhou, China

Linked Papers

2024-06-01

Surgery versus no surgery in platinum-sensitive relapsed ovarian cancer: final overall survival analysis of the SOC-1 randomized phase 3 trial

Surgery for platinum-sensitive, relapsed ovarian cancer (PSROC) is widely practiced but had contradictory survival outcomes in previous studies. In this multicenter, open-label, phase 3 trial, women with PSROC, and having had one previous therapy and no platinum-based chemotherapy (platinum-free interval) of 6 months or more, were randomly assigned to either the surgery group (182 patients) or the no-surgery group (control) (175 patients). Patients with resectable diseases were eligible according to the international model (iMODEL), combined with a positron emission tomography-computed tomography imaging. Overall survival (OS) and progression-free survival were coprimary endpoints in hierarchical testing, and a significantly longer progression-free survival with surgery was previously reported. Final analysis of OS was planned at data maturity of 59%. Between 19 July 2012 and 3 June 2019, 357 patients were enrolled. Median follow-up was 82.5 months. Median OS was 58.1 months with surgery and 52.1 months for control (hazard ratio (HR) 0.80, 95% confidence interval (CI) 0.61-1.05, P = 0.11). The predefined threshold for statistical significance was not met, but prespecified sensitivity analysis was performed. Overall, 61 of 175 (35%) patients in control had crossed over to surgery following subsequent relapse, and adjusted HR for death in the surgery group compared with control was 0.76, 95% CI 0.58-0.99. In subgroup analysis of relapse sites by imaging, median survival was not estimable in the surgery group and was 69.5 months in control in patients with 60 months in the surgery group as compared with five of 175 (2.9%) patients in the control group. In patients with PSROC, surgery did not increase OS in the intention-to-treat population but resulted in a prolongation of survival following adjustment of crossover.ClinicalTrials.gov registration: NCT01611766 .

2021-03-08

Secondary cytoreduction followed by chemotherapy versus chemotherapy alone in platinum-sensitive relapsed ovarian cancer (SOC-1): a multicentre, open-label, randomised, phase 3 trial

The benefits of secondary cytoreduction for platinum-sensitive relapsed ovarian cancer are still widely debated. We aimed to assess the efficacy of secondary cytoreduction plus chemotherapy versus chemotherapy alone in this patient population. This multicentre, open-label, randomised, controlled, phase 3 trial (SOC-1), was done in four primarily academic centres in China (two in Shanghai, one in Hangzhou, and one in Guangzhou). Eligible patients were women aged 18 years and older with platinum-sensitive relapsed epithelial ovarian cancer with a platinum-free interval of at least 6 months after the end of first-line platinum-based chemotherapy and were predicted to have potentially resectable disease according to the international model (iMODEL) score and PET-CT imaging. iMODEL score was calculated using six variables: International Federation of Gynecology and Obstetrics stage, residual disease after primary surgery, platinum-free interval, Eastern Cooperative Oncology Group performance status, serum level of cancer antigen 125 at recurrence, and presence of ascites at recurrence. An iMODEL score of 4·7 or lower predicted a potentially complete resection. As per a protocol amendment, patients with an iMODEL score of more than 4·7 could only be included if the serum level of cancer antigen 125 was more than 105 U/mL, but the principal investigators assessed the disease to be resectable by PET-CT. Eligible participants were randomly assigned (1:1) via a permuted block design (block size of six) and stratified by study centre, iMODEL score, residual disease at primary surgery, and enrolment in the Shanghai Gynecologic Oncology Group SUNNY trial, to undergo secondary cytoreductive surgery followed by intravenous chemotherapy (six 3-weekly cycles of intravenous paclitaxel [175 mg/m Between July 19, 2012, and June 3, 2019, 357 patients were recruited and randomly assigned to the surgery group (182) or the no surgery group (175; ITT population). Median follow-up was 36·0 months (IQR 18·1-58·3). In the no surgery group, 11 (6%) of 175 participants had secondary cytoreduction during second-line therapy while 48 (37%) of 130 participants who had disease progression crossed-over and had surgery at a subsequent recurrence. Median progression-free survival was 17·4 months (95% CI 15·0-19·8) in the surgery group and 11·9 months (10·0-13·8) in the no surgery group (hazard ratio [HR] 0·58; 95% CI 0·45-0·74; p<0·0001). At the interim overall survival analysis, median overall survival was 58·1 months (95% CI not estimable to not estimable) in the surgery group and 53·9 months (42·2-65·5) in the no surgery group (HR 0·82, 95% CI 0·57-1·19). In the safety population, nine (5%) of 172 patients in the surgery group had grade 3-4 surgical morbidity at 30 days, and no patients in either group had died at 60 days after receiving assigned treatment. The most common grade 3-4 adverse events during chemotherapy were neutropenia (29 [17%] of 166 patients in the surgery group vs 19 [12%] of 156 patients in the no surgery group), leucopenia (14 [8%] vs eight [5%]), and anaemia (ten [6%] vs nine [6%]). Four serious adverse events occurred, all in the surgery group. No treatment-related deaths occurred in either group. Secondary cytoreduction followed by chemotherapy was associated with significantly longer progression-free survival than was chemotherapy alone in patients with platinum-sensitive relapsed ovarian cancer, and patients should be counselled about the option of secondary cytoreduction in specialised centres. Long-term survival outcomes will be assessed using mature data on overall survival. Zhongshan Development Program. For the Chinese translation of the abstract see Supplementary Materials section.