Refining Adjuvant Treatment in Endometrial Cancer Based on Molecular Features
- Conditions
- Endometrial Cancer
- Interventions
- Other: ObservationRadiation: Pelvic external beam radiotherapyRadiation: Vaginal brachytherapyDrug: Chemotherapy
- Registration Number
- NCT05255653
- Lead Sponsor
- Leiden University Medical Center
- Brief Summary
The RAINBO umbrella program consists of four clinical trials investigating new adjuvant therapies in endometrial cancer patients. Eligible patients will be assigned to one of the four RAINBO trials based on the molecular profile of their cancer:
* p53 abnormal endometrial cancer patients to the p53abn-RED trial
* mismatch repair deficient endometrial cancer patients to the MMRd-GREEN trial
* no specific molecular profile endometrial cancer patients to NSMP-ORANGE trial
* POLE mutant endometrial cancer patients to the POLEmut-BLUE trial
- Detailed Description
The p53abn-RED trial (NCT05255653-1) is an international, multicenter, phase III randomised trial wherein adjuvant chemoradiation followed by olaparib for one year is compared to adjuvant chemoradiation.
The MMRd-GREEN trial (NCT05255653-2) is an international, multicenter, phase III randomised trial wherein adjuvant pelvic external beam radiotherapy combined with and followed by durvalumab for one year is compared to adjuvant pelvic external beam radiotherapy with or without chemotherapy.
The NSMP-ORANGE trial (NCT05255653-3) is an international, multicenter, phase III randomised trial wherein adjuvant pelvic external beam radiotherapy followed by progestogens for two years is compared to adjuvant chemoradiation.
The POLEmut-BLUE trial (NCT05255653-4) is an international, multicenter, single arm, phase II trial wherein safety of de-escalation of adjuvant therapy is investigated: no adjuvant therapy for stage I-II disease and no adjuvant therapy or pelvic external beam radiotherapy only for stage III disease.
The overarching RAINBO research project will combine the data and tumor material of the four RAINBO clinical trials to perform translational research and compare molecular profile-based adjuvant therapy to standard adjuvant therapy in terms of effectiveness, toxicity, quality of life and cost utility.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Female
- Target Recruitment
- 1615
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description p53abn-RED trial: experimental Olaparib Adjuvant radiotherapy and chemotherapy followed by olaparib (lynparza), 300 mg twice daily, for one year p53abn-RED trial: experimental Pelvic external beam radiotherapy Adjuvant radiotherapy and chemotherapy followed by olaparib (lynparza), 300 mg twice daily, for one year p53abn-RED trial: control Pelvic external beam radiotherapy Adjuvant radiotherapy and chemotherapy p53abn-RED trial: control Vaginal brachytherapy Adjuvant radiotherapy and chemotherapy MMRd-GREEN trial: experimental Pelvic external beam radiotherapy Adjuvant radiotherapy combined with and followed by durvalumab, 1500 mg intravenous once every 4 weeks for in total 1 year (13 cycles) p53abn-RED trial: experimental Chemotherapy Adjuvant radiotherapy and chemotherapy followed by olaparib (lynparza), 300 mg twice daily, for one year p53abn-RED trial: experimental Vaginal brachytherapy Adjuvant radiotherapy and chemotherapy followed by olaparib (lynparza), 300 mg twice daily, for one year p53abn-RED trial: control Chemotherapy Adjuvant radiotherapy and chemotherapy MMRd-GREEN trial: experimental Durvalumab Adjuvant radiotherapy combined with and followed by durvalumab, 1500 mg intravenous once every 4 weeks for in total 1 year (13 cycles) MMRd-GREEN trial: experimental Vaginal brachytherapy Adjuvant radiotherapy combined with and followed by durvalumab, 1500 mg intravenous once every 4 weeks for in total 1 year (13 cycles) MMRd-GREEN trial: control Pelvic external beam radiotherapy Adjuvant pelvic external beam radiotherapy +/- chemotherapy MMRd-GREEN trial: control Chemotherapy Adjuvant pelvic external beam radiotherapy +/- chemotherapy NSMP-ORANGE trial: experimental Megestrol Acetate Adjuvant radiotherapy followed by oral progestagens (medroxyprogesterone acetate or megestrol acetate) for two years NSMP-ORANGE trial: experimental Vaginal brachytherapy Adjuvant radiotherapy followed by oral progestagens (medroxyprogesterone acetate or megestrol acetate) for two years MMRd-GREEN trial: control Vaginal brachytherapy Adjuvant pelvic external beam radiotherapy +/- chemotherapy NSMP-ORANGE trial: experimental Pelvic external beam radiotherapy Adjuvant radiotherapy followed by oral progestagens (medroxyprogesterone acetate or megestrol acetate) for two years NSMP-ORANGE trial: experimental Medroxyprogesterone Acetate Adjuvant radiotherapy followed by oral progestagens (medroxyprogesterone acetate or megestrol acetate) for two years NSMP-ORANGE trial: control Chemotherapy Adjuvant radiotherapy and chemotherapy NSMP-ORANGE trial: control Pelvic external beam radiotherapy Adjuvant radiotherapy and chemotherapy NSMP-ORANGE trial: control Vaginal brachytherapy Adjuvant radiotherapy and chemotherapy POLEmut-BLUE trial: main cohort Observation No adjuvant therapy in women with: * stage IA (not confined to polyp), grade 3, pN0, with or without LVSI * stage IB, grade 1 or 2, pNx/N0, with or without LVSI * stage IB, grade 3, pN0, without substantial LVSI * stage II (microscopic), grade 1 or 2, pN0, without substantial LVSI POLEmut-BLUE trial: exploratory cohort Pelvic external beam radiotherapy No adjuvant therapy or vaginal brachytherapy or pelvic external beam radiotherapy in women with: * stage IA grade 3 - stage III not included in main cohort of the POLEmut-BLUE trial * Multiple molecular classifiers Stage IA (not confined to polyp), grade 3 - Stage III POLEmut-BLUE trial: exploratory cohort Vaginal brachytherapy No adjuvant therapy or vaginal brachytherapy or pelvic external beam radiotherapy in women with: * stage IA grade 3 - stage III not included in main cohort of the POLEmut-BLUE trial * Multiple molecular classifiers Stage IA (not confined to polyp), grade 3 - Stage III POLEmut-BLUE trial: exploratory cohort Observation No adjuvant therapy or vaginal brachytherapy or pelvic external beam radiotherapy in women with: * stage IA grade 3 - stage III not included in main cohort of the POLEmut-BLUE trial * Multiple molecular classifiers Stage IA (not confined to polyp), grade 3 - Stage III
- Primary Outcome Measures
Name Time Method p53abn-RED trial 3 years Recurrence-free survival
MMRd-GREEN trial 3 years Recurrence-free survival
NSMP-ORANGE trial 3 years Recurrence-free survival
POLEmut-BLUE trial 3 years Pelvic recurrence-free survival
- Secondary Outcome Measures
Name Time Method Endometrial cancer-specific survival 3 years, 5 years All RAINBO trials
Overall survival 3 years, 5 years All RAINBO trials
Treatment-related toxicity - according to CTCAE v5.0 3 years, 5 years All RAINBO trials
Recurrence-free survival 5 years All RAINBO trials
Pelvic recurrence-free survival 5 years All RAINBO trials
Vaginal recurrence-free survival 3 years, 5 years All RAINBO trials
Health-related quality of life - Assessed using the EORTC QLQ-C30 questionnaire 3 years, 5 years All RAINBO trials
Health-related quality of life - Assessed using the EORTC QLQ-EN24 questionnaire 3 years, 5 years All RAINBO trials
Trial Locations
- Locations (14)
The POLEmut-BLUE trial: Princess Margaret Cancer Centre, University of Toronto
🇨🇦Toronto, Canada
Medisch Spectrum Twente
🇳🇱Enschede, Netherlands
The MMRd-GREEN trial: Leiden University Medical Center
🇳🇱Leiden, Netherlands
The POLEmut-BLUE trial: University of British Columbia
🇨🇦Vancouver, Canada
The p53abn-RED trial: Institute Gustave Roussy
🇫🇷Villejuif, France
Erasmus Medical Center
🇳🇱Rotterdam, Netherlands
The NSMP-ORANGE trial: Barts Health NHS Trust
🇬🇧London, United Kingdom
The NSMP-ORANGE trial: Manchester Academic Health Science Centre, St Mary's Hospita
🇬🇧Manchester, United Kingdom
Amsterdam University Medical Center
🇳🇱Amsterdam, Netherlands
Amphia Ziekenhuis
🇳🇱Breda, Netherlands
Instituut Verbeeten
🇳🇱Breda, Netherlands
Catharina Ziekenhuis
🇳🇱Eindhoven, Netherlands
Haags Medisch Centrum
🇳🇱Den Haag, Netherlands
Universitair Medisch Centrum Groningen
🇳🇱Groningen, Netherlands