Refining Adjuvant Treatment in Endometrial Cancer Based on Molecular Features
RAINBO
3 other identifiers
interventional
1,615
4 countries
14
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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Nov 2021
Longer than P75 for phase_2
14 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
November 11, 2021
CompletedFirst Submitted
Initial submission to the registry
February 1, 2022
CompletedFirst Posted
Study publicly available on registry
February 24, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2030
ExpectedStudy Completion
Last participant's last visit for all outcomes
January 1, 2031
November 29, 2024
October 1, 2024
8.1 years
February 1, 2022
November 26, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
p53abn-RED trial
Recurrence-free survival
3 years
MMRd-GREEN trial
Recurrence-free survival
3 years
NSMP-ORANGE trial
Recurrence-free survival
3 years
POLEmut-BLUE trial
Pelvic recurrence-free survival
3 years
Secondary Outcomes (8)
Recurrence-free survival
5 years
Pelvic recurrence-free survival
5 years
Vaginal recurrence-free survival
3 years, 5 years
Endometrial cancer-specific survival
3 years, 5 years
Overall survival
3 years, 5 years
- +3 more secondary outcomes
Study Arms (8)
p53abn-RED trial: experimental
EXPERIMENTALAdjuvant radiotherapy and chemotherapy followed by olaparib (lynparza), 300 mg twice daily, for one year
p53abn-RED trial: control
ACTIVE COMPARATORAdjuvant radiotherapy and chemotherapy
MMRd-GREEN trial: experimental
EXPERIMENTALAdjuvant 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
ACTIVE COMPARATORAdjuvant pelvic external beam radiotherapy +/- chemotherapy
NSMP-ORANGE trial: experimental
EXPERIMENTALAdjuvant radiotherapy followed by oral progestagens (medroxyprogesterone acetate or megestrol acetate) for two years
NSMP-ORANGE trial: control
ACTIVE COMPARATORAdjuvant radiotherapy and chemotherapy
POLEmut-BLUE trial: main cohort
OTHERNo 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
OTHERNo 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
Interventions
45.0-48.6 Gy; 1.8-2.0 Gy per fraction, 5 fractions a week
Preferably concurrent and adjuvant according to the PORTEC-3 schedule: two cycles of intravenous cisplatin 50mg/m² in the first and fourth week of the pelvic external beam radiotherapy followed by four cycles of intravenous carboplatin AUC 5 and paclitaxel 175 mg/m² at 21-day intervals.
1500 mg intravenous once every 4 weeks for in total 1 year (13 cycles) starting within the first week of radiotherapy,
Oral medroxyprogesterone acetate for two years
Oral medroxyprogesterone acetate for two years
Vaginal brachytherapy is to be considered in patients with documented cervical stromal involvement and/or substantial LVSI. Brachytherapy is given with a vaginal cylinder or vaginal ovoids or ring applicator, according to the center's standard technique. When using a cylinder, the active length will ideally be 2-3 cm, with the reference isodose covering the proximal 2.5-3 cm of the vagina. High-dose-rate (HDR) and pulse-dose-rate (PDR) schedules are permitted, which deliver an EQD2 equivalent dose of 10-14 Gy at 5 mm from the vaginal mucosa (to obtain a cumulative EDQ2 of 60 Gy at 5 mm).
No adjuvant therapy
Eligibility Criteria
You may not qualify if:
- Histologically confirmed diagnosis of endometrial cancer (EC) of the following histotypes: endometrioid endometrial carcinoma, serous endometrial carcinoma, uterine clear cell carcinoma, dedifferentiated and undifferentiated endometrial carcinoma, uterine carcinosarcoma and mixed endometrial carcinomas of the aforementioned histotypes.
- Full molecular classification performed following the diagnostic algorithm described in WHO 2020 (5th Edition, IARC, Lyon, 2020)
- Hysterectomy and bilateral salpingo-oophorectomy with or without lymphadenectomy or sentinel node biopsy, without macroscopic residual disease after surgery
- No distant metastases as determined by pre-surgical or post-surgical imaging (CT scan of chest, abdomen and pelvis or whole-body PET-CT scan)
- WHO performance status 0, 1 or 2
- Expected start of adjuvant treatment (if applicable) within 10 weeks after surgery
- Patients must be accessible for treatment and follow-up
- Written informed consent for participation in one of the RAINBO trials, permission for the contribution of a tissue block for translation research and permission for the use and sharing of data for the overarching research project according to the local Ethics Committee requirements.
- History of another primary malignancy, except for non-melanoma skin cancer, in the past 5 years
- Prior pelvic radiation
- The p53abn-RED trial
- p53 abnormal EC
- Histologically confirmed stage I (with invasion) II or III EC
- WHO Performance score 0-1
- Body weight \> 30 kg
- +71 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Leiden University Medical Centerlead
- Institute Gustave Roussy (sponsor p53abn-RED trial)collaborator
- Leiden University Medical center (sponsor MMRd-GREEN trial)collaborator
- University College London (sponsor NSMP-ORANGE trial)collaborator
- Canadian Clinical Trials Group (sponsor POLEmut-BLUE trial)collaborator
- Dutch Gynaecological Oncology Groupcollaborator
- Comprehensive Cancer Centre The Netherlandscollaborator
- Cancer Research UK & UCL Cancer Trials Centrecollaborator
- Dutch Cancer Societycollaborator
- AstraZenecacollaborator
- National Cancer Institute, Francecollaborator
- Canadian Institutes of Health Research (CIHR)collaborator
Study Sites (14)
The POLEmut-BLUE trial: Princess Margaret Cancer Centre, University of Toronto
Toronto, Canada
The POLEmut-BLUE trial: University of British Columbia
Vancouver, Canada
The p53abn-RED trial: Institute Gustave Roussy
Villejuif, France
Amsterdam University Medical Center
Amsterdam, Netherlands
Amphia Ziekenhuis
Breda, Netherlands
Instituut Verbeeten
Breda, Netherlands
Catharina Ziekenhuis
Eindhoven, Netherlands
Medisch Spectrum Twente
Enschede, Netherlands
Universitair Medisch Centrum Groningen
Groningen, Netherlands
The MMRd-GREEN trial: Leiden University Medical Center
Leiden, 2333ZA, Netherlands
Erasmus Medical Center
Rotterdam, Netherlands
Haags Medisch Centrum
The Hague, 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
Related Publications (3)
IMPLEMENTATION OF COLLABORATIVE TRANSLATIONAL RESEARCH (TRANSPORTEC) FINDINGS IN AN INTERNATIONAL ENDOMETRIAL CANCER CLINICAL TRIALS PROGRAM (RAINBO). T Bosse, M Powell, E Crosbie, A Leary, J Kroep, K Han, J Mcalpine, N Horeweg, S De Boer, M De Bruyn, R Nout, V Smit, HW Nijman, N Singh, H Mackay, R Edmondson, L Mileshkin, D Church, H Kitchener, CL Creutzberg. Int J Gynecol Cancer 2021;31(Suppl 3):A1-A395. DOI: 10.1136/ijgc-2021-ESGO.171
BACKGROUNDRAINBO Research Consortium. Refining adjuvant treatment in endometrial cancer based on molecular features: the RAINBO clinical trial program. Int J Gynecol Cancer. 2023 Jan 3;33(1):109-117. doi: 10.1136/ijgc-2022-004039.
PMID: 36600534BACKGROUNDSecord AA, Powell MA, McAlpine J. Molecular Characterization and Clinical Implications of Endometrial Cancer. Obstet Gynecol. 2025 Nov 1;146(5):660-671. doi: 10.1097/AOG.0000000000006080. Epub 2025 Sep 18.
PMID: 40966692DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Alexandra Leary, Md PhD
Institute Gustave Roussy, Villejuif, France (p53abn-RED trial)
- PRINCIPAL INVESTIGATOR
Judith R Kroep, MD PhD
Leiden University Medical Center, Leiden, The Netherlands (MMRd-GREEN trial)
- PRINCIPAL INVESTIGATOR
Melanie E Powell, Md PhD
Barts Health NHS Trust, London, United Kingdom (NSMP-ORANGE trial)
- PRINCIPAL INVESTIGATOR
Emma J Crosbie, Md PhD
St Mary's Hospital, Manchester, United Kingdom (NSMP-ORANGE trial)
- PRINCIPAL INVESTIGATOR
Kathy Han, Md PhD
Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada (POLEmut-BLUE trial)
- PRINCIPAL INVESTIGATOR
Jessica N McAlpine, Md PhD
University of British Columbia,Vancouver, Canada (POLEmut-BLUE trial)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- prof
Study Record Dates
First Submitted
February 1, 2022
First Posted
February 24, 2022
Study Start
November 11, 2021
Primary Completion (Estimated)
January 1, 2030
Study Completion (Estimated)
January 1, 2031
Last Updated
November 29, 2024
Record last verified: 2024-10
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL
- Time Frame
- The study protocols of the four trials will be made made available on the trial's websites by the time the trials open
- Access Criteria
- Public
Following the planned translational work in the RAINBO programme and publications, the translational research (TR) committee will open up the sample collection to external researchers. Access will be granted following completion of a research proposal form and approval by the TR committee chaired by Dr. Tjalling Bosse. All external researchers will be expected to demonstrate funding for their project and ethics approval. Data will be made available as required through data sharing agreements. The following will be reviewed when considering applications for data sharing and sample access: data and sample use is in-keeping with patient consent, the proposed project has scientific value, with defined objectives and study plan, trial data are appropriate for the intended purpose, acknowledgement of the RAINBO Programme in all publications that arise from the data sharing, compliance with legal and regulatory requirements as applicable and patient confidentiality maintained at all times.