Biomarker Guided Treatment in Gynaecological Cancer

NCT02543710RecruitingPHASE4INTERVENTIONAL

Summary

MoMaTEC2 aims to test, in clinically oriented studies, the applicability of already identified and promising molecular biomarkers, to promote individualisation of treatment for patients with endometrial cancer. Predominantly, but not exclusively, such biomarkers have shown to be interesting in retrospective analysis of our large prospectively collected MoMaTEC1 series. Part 1: Performance of a phase 4 implementation trial for optimised stratification of surgical treatment, specifically the performance of (para-aortic and pelvic) lymphadenectomy guided by validated biomarkers. Part 2: Performance of a phase 2b clinical biomarker study to evaluate the predictive potential of the biomarker stathmin for taxane treatment response in endometrial and ovarian cancer. In this study stathmin will be used as integrated biomarker.

Key Facts

Lead Sponsor

Haukeland University Hospital

Enrollment

1300

Start Date

2015-10-01

Completion Date

2020-12-01

Study Type

INTERVENTIONAL

Official Title

Biomarker Guided Treatment in Gynaecological Cancer

Interventions

Biomarker (ER/PR) guided lymphadenectomyBiomarker guided weekly taxane treatment in endometrial/ ovarian cancer

Conditions

Endometrial Cancer

Eligibility

Age Range

18 Years – 95 Years

Sex

FEMALE

Inclusion Criteria part 1:

All patients referred to a participating research centre with suspicion of or confirmed endometrial cancer.

Exclusion Criteria part 1:

1. Patients who do not have endometrial cancer
2. Patients who will or cannot give informed consent (including language barriers)
3. Patients \<18 years of age
4. Patients who will not get surgical treatment for their endometrial cancer

Inclusion criteria part 2:

1. Patients with endometrial or epithelial ovarian cancer who following routine clinical guidelines are offered weekly taxane (paclitaxel) treatment. This will often be a third or fourth line treatment, i.e. patients with advanced disease.
2. Technical possibility to obtain a new tissue biopsy to determine stathmin level in the tumour recurrence.

Exclusion criteria part 2:

1. Patients not suffering from endometrial or epithelial ovarian cancer
2. Patients \<18 years of age
3. Patients who do not agree to the proposed treatment or will receive (part of) the treatment in a non-participating centre
4. Patients who cannot or do not want to give informed consent (including language barriers)

Outcome Measures

Primary Outcomes

number of recurrences after primary treatment

The percentage of lymphadenectomy can be reduced safely and significantly, from 70% (MoMaTEC1 study results) to 30% in the MoMaTEC2 study through a better risk stratification of patients, especially better identification of low risk patients. Additionally The percentage of patients who need to be subjected to adjuvant (chemo) therapy can be reduced similarly from 20 to 10%, based on the same, optimised risk stratification and better identification of low risk patients. Patients will be rigorously followed during 5 years to detect any unexpected increase in the percentage of patients suffering a recurrence compared to the historical MoMaTEC1 cohort.

Time frame: 5 year after diagnosis

stathmin levels

stathmin level will be measured in metastatic tissue and related to response to treatment using Response Evaluation Criteria In Solid Tumors (RECIST) criteria

Time frame: duration of complete or partial treatment response in metastatic setting (expected duration less than one year)

Secondary Outcomes

Quality of life measurements

Quality of life will be measured through validated questionnaires (EORTC QLQ-C30 and EORTC QLQ-EN24).

Time frame: 5 years post treatment

correlation of stathmin llevels in tumor, urine and blood

stathmin tumor levels, urine levels and blood levels will be correlated.

Time frame: duration of complete or partial treatment response in metastatic setting (expected duration less than one year)

Locations

Radboud university hospital, Nijmegen, Netherlands

Women's hospital, Haukeland university hospital, Bergen, Norway

Ålesund hospital, Ålesund, Norway

Førde central hospital, Førde, Norway

Sørlandet hospital, Kristiansand, Norway

Akershus University hospital, Oslo, Norway

Stavanger university hospital, Stavanger, Norway

St Olav university hospital, Trondheim, Norway

Spsk No 1, Lublin, Poland

Linked Papers

2021-08-13

Longitudinal effects of adjuvant chemotherapy and lymph node staging on patient-reported outcomes in endometrial cancer survivors: a prospective cohort study

Most patients with endometrial cancer with localized disease are effectively treated and survive for a long time. The primary treatment is hysterectomy, to which surgical staging procedures may be added to assess the need for adjuvant therapy. Longitudinal data on patient-reported outcomes comparing different levels of primary treatment are lacking, especially when adjuvant radiotherapy is omitted. We assessed the impact of lymphadenectomy and adjuvant chemotherapy on patient-reported symptoms, function, and quality of life. We hypothesized that these treatment modalities would substantially affect patient-reported outcomes at follow-up. We prospectively included patients with endometrial cancer enrolled in the ongoing MoMaTEC2 study (ClinicalTrials.gov Identifier: NCT02543710). Patients were asked to complete the patient-reported outcome questionnaires European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire EN24 preoperatively and at 1 and 2 years of follow-up. Functional domains and symptoms were analyzed for the whole cohort and by treatment received. To assess the effect of the individual treatment modifications, we used mixed regression models. Baseline data were available for 448 patients. Of these patients, 339 and 219 had reached 1-year follow-up and 2-year follow-up, respectively. Treatment included hysterectomy (plus bilateral salpingo-oophorectomy) alone (n=177), hysterectomy and lymph node staging without adjuvant therapy (n=133), or adjuvant chemotherapy irrespective of staging procedure (n=138). Overall, patients reported improved global health status and quality of life (+9 units; P<.001), increased emotional and social functioning, and increased sexual interest and activity (P<.001 for all) from baseline to year 1, and these outcomes remained stable at year 2. Means of functional scales and quality of life were similar to age- and sex-weighted reference cohorts. Mean tingling and numbness and lymphedema increased after treatment. The group who received adjuvant chemotherapy had a larger mean reduction in physical functioning (-6 vs +2; P=.002) at year 1, more neuropathy (+30 vs +5; P<.001; year 1) at years 1 and 2, and more lymphedema at year 1 (+11 vs +2; P=.007) than the group treated with hysterectomy and salpingo-oophorectomy only. In patients not receiving adjuvant chemotherapy, patient-reported outcomes were similar regardless of lymph node staging procedures. Adjuvant chemotherapy independently increased fatigue, lymphedema, and neuropathy in mixed regression models. Patients with endometrial cancer receiving adjuvant chemotherapy reported significantly reduced functioning and more symptoms up to 2 years after treatment. For patients treated by surgery alone, surgical staging did not seem to affect the quality of life or symptoms to a measurable degree at follow-up. Therefore, subjecting patients to lymph node removal to tailor adjuvant therapy seems justified from the patient's viewpoint; however, efforts should increase to find alternatives to traditional chemotherapy.

Linked Investigators

Camilla Krakstad

David Forsse

Margaret Sævik-Lode

Biomarker Guided Treatment in Gynaecological Cancer