Endometrial CancerPhase 3RAINBO-GREENNCT05255653
Refining Adjuvant Treatment IN Endometrial Cancer Based On Molecular Features
A Phase 3 study testing Pelvic external beam radiotherapy, Chemotherapy and Durvalumab in people with Endometrial Cancer, run by Leiden University Medical Center at 60 sites in 7 countries.
Trial summary
RAINBO MMRd-GREEN 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Endometrial Cancer
- What is being tested?
- Pelvic external beam radiotherapy, Chemotherapy and Durvalumab
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 316 participants
- Where
- 60 sitesin 7 countries
- Study dates
- 11 Nov 2021to 1 Jan 2031
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
- TLH-BSO or TAH-BSO 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/MRI scan of chest, abdomen and pelvis or PET-CT scan)
- Age ≥ 18 years
- Expected start of adjuvant treatment (if applicable) within 10 weeks after surgery
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- 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.
- Written informed consent
- WHO Performance score 0-1
- Histologically confirmed FIGO 2009 stage IB/II with LVSI, stage III, or stage IV with limited pelvic peritoneal involvement (FIGO 2023 stage IB with LVSI, stage II with myometrial or cervical stroma involvement and LVSI, or stage III disease)
- Molecular classification: MMRd EC*
- No prior pelvic radiotherapy
- Body weight > 30 kg
- Adequate systemic organ function:
- Creatinine clearance (> 40 cc/min): Measured creatinine clearance (CL) >40 mL/min or Calculated creatinine CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance.
- Adequate bone marrow function : hemoglobin >9.0 g/dl, Absolute neutrophil count (ANC) ≥1.0 x 109/l, platelet count ≥75 x 109/l.
- Adequate liver function: Bilirubin ≤1.5 x institutional upper limit of normal (ULN). <<This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.>>
- ALT (SGPT) and/or AST (SGOT) ≤2.5 x ULN
Who cannot join
- History of another primary malignancy, except for non-melanoma skin cancer, in the past 5 years
- Prior pelvic radiation
- The MMRd-GREEN trial
- Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of Investigational medicinal product (IMP).
- History of allogenic organ transplantation.
- Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
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- Any previous treatment with a PD(L)1 inhibitor, including durvalumab.
- Receipt of live attenuated vaccine within 30 days prior to the first dose of durvalumab. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IMP.
- Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab with the exceptions of :
- Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection).
- Systemic corticosteroids at physiologic doses not to exceed <<10 mg/day>> of prednisone or its equivalent.
- Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
- History of active primary immunodeficiency
- Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome. The following are exceptions to this criterion:
- Patients with vitiligo or alopecia
- Patients with hypothyroidism (e.g., following Hashimoto syndrome)stable on hormone replacement
- Any chronic skin condition that does not require systemic therapy
- Patients without active disease in the last 5 years may be included but only after consultation with the study physician.
- Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immuno-deficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
- Medical or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or sign meaningful informed consent.
Trial locations and contacts
60 sites in 7 countries. Contact the study team or a site near you to ask about taking part.
Annet Roodvoets contact
60 sites in 7 countries
Canada15 sites, 15 recruiting
- Recruiting
Juravinski Cancer Center
Hamilton
Nidhi Kumar-Tyagi, kumarn@hhsc.ca;nguyenjmv@hhsc.ca
- Recruiting
BCCA Kelowna
Kelowna
Flavia De Angelis, flavia.deangelis@bccancer.bc.ca
- Recruiting
Kingston Health Sciences Centre
Kingston
Rania Chehade, rania.chehade@kingstonhsc.ca
- Recruiting
London Regional Cancer Centre
London
Stephen Welch, stephen.welch@lhsc.on.ca
- Recruiting
Centre Hospitalier de Universite de Montreal
Montreal
Vanessa Samouelian, vanessa.samouelian.med@ssss.gouv.qc.ca
- Recruiting
Jewish General Hospital
Montreal
Susie Lau, susie.lau@mcgill.ca
- Recruiting
Maisonneuve-Rosemont Hospital
Montreal
Suzanne Fortin, suzanne.fortin.med@ssss.gouv.qc.ca
- Recruiting
Allan Blair Cancer Centre
Regina
Maryam AlHayki, maryalhayki@gmail.com
- Recruiting
Saint John Regional Center
Saint John
Marissa Sherwood, marissa.sherwood@horizonnb.ca
- Recruiting
Saskatoon Cancer Centre
Saskatoon
Jennifer Brownbroderick, jennifer.BrownBroderick@saskcancer.ca
- Recruiting
Centre hospitalier universitaire de Sherbrooke
Sherbrooke
Mathieu Viau, mathieu.viau@usherbrooke.ca
- Recruiting
Princess Margaret Cancer Centre
Toronto
Kathy Han, MD PhD, Kathy.Han@rmp.uhn.ca
- Recruiting
Sunnybrook Health Science Centre
Toronto
Eric Leung, eric.leung@sunnybrook.ca
- Recruiting
BC Cancer Vancouver
Vancouver
Corinne Mauricedror, corinne.mauricedror@bccancer.bc.ca
- Recruiting
BCCA Victoria
Victoria
Richard Gagnon, richard.gagnon@bccancer.bc.ca
Netherlands13 sites, 13 recruiting
- Recruiting
Amsterdam University Medical Center
Amsterdam
Jacqueline Tromp, j.m.tromp@amsterdamumc.nl
Jasper LA Vleugels, MD PhD
- Recruiting
Amphia Ziekenhuis
Breda
Joan Heijns, MD PhD, jheijns@amphia.nl
- Recruiting
Instituut Verbeeten
Breda
Frederieke Koppe, koppe.f@bvi.nl
- Recruiting
Catharina Ziekenhuis
Eindhoven
Annemarie Thijs, MD PhD, annemarie.thijs@catharinaziekenhuis.nl
- Recruiting
Medisch Spectrum Twente
Enschede
Machteld Wymenga, MD PhD, a.wymenga@mst.nl
- Recruiting
Universitair Medisch Centrum Groningen
Groningen
Ann KL Reyners, MD PhD, a.k.l.reyners@umcg.nl
- Recruiting
MCL
Leeuwarden
Marco Polée, MD PhD, m.polee@mcl.nl
- Recruiting
RIF
Leeuwarden
Marianne de Jong, m.a.a.jong@skf-rif.nl
- Recruiting
Leiden University Medical Center
Leiden, 2333ZA
Judith R Kroep, MD PhD, +31 71 526 5095, j.r.kroep@lumc.nl
- Recruiting
Maastro
Maastricht
Nienke Kuijsters, nienke.kuijsters@maastro.nl
- Recruiting
MUMC
Maastricht
Tonneke Beijers, MD PhD, tonneke.beijers@mumc.nl
- Recruiting
Erasmus Medical Center
Rotterdam
Ingrid Boere, Md PhD, i.boere@erasmusmc.nl
- Recruiting
UMCU
Utrecht
Inge Baas, MD PhD, I.O.Baas-3@umcutrecht.nl
Germany11 sites, 11 recruiting
- Recruiting
Evangelisches Waldkrankenhaus Spandau Berlin
Berlin
Katharina Carrizo, katharina.carrizo@jsd.de
- Recruiting
Klinikum Lippe
Detmold
Beyhan Ataseven, beyhan.ataseven@klinikum-lippe.de
- Recruiting
Universitätsklinikum Hamburg-Eppendorf
Hamburg
Barbara Schmalfeldt, b.schmalfeldt@uke.de
- Recruiting
Universitätsklinikum Heidelberg
Heidelberg
Thomas Deutsch, Thomas.Deutsch@umm.de
- Recruiting
Klinikum Kempten
Kempten
Ricardo Felberbaum, ricardo.felberbaum@klinikverbund-allgaeu.de
- Recruiting
Ludwigsburg
Ludwigsburg
Claudia Haenle, claudia.haenle@rkh-gesundheit.de
- Recruiting
Rotkreuzklinikum München
München
Moritz Hamann, moritz.hamann@swmbrk.de
- Recruiting
Diakoneo Diakonie-Klinikum Schwäbisch Hall
Schwäbisch Hall
Stefan Kommoss, stefan.kommoss@diak-klinikum.de
- Recruiting
Universitätsklinik Tübingen
Tübingen
Tobias Engler, tobias.engler@med.uni-tuebingen.de
- Recruiting
Universitätsklinikum Ulm
Ulm
Sabine Heublein, sabine.heublein@uniklinik-ulm.de
- Recruiting
Klinikum Worms
Worms
Matthias Koegel, matthias.koegel@klinikum-worms.de
France10 sites, 10 recruiting
- Recruiting
CHU Jean Minjoz
Besançon
Laura Mansi, lmansi@chu-besancon.fr
- Recruiting
Institut Bergonie
Bordeaux
Coriolan LeBreton, c.lebreton@bordeaux.unicancer.fr
- Recruiting
Institut Leon Berard
Lyon
Olivia le Saux, olivia.lesaux@lyon.unicancer.fr
- Recruiting
Institut Paoli Calmattes-Marseille
Marseille
Renaud Sabatier, SABATIERR@ipc.unicancer.fr
- Recruiting
Institut du cancer de Montpellier
Montpellier
Stanislas Quesada, stanislas.quesada@icm.unicancer.fr
- Recruiting
Centre Antoine Lacassagne
Nice
Philippe Follana, philippe.follana@nice.unicancer.fr
- Recruiting
ICO Saint Herblain
Saint-Herblain
Jean-Sebastien Frenel, Jean-Sebastien.Frenel@ico.unicancer.fr
- Recruiting
Clinique Sainte-Anna
Strasbourg
Youssef Tazi, ytazi@solcrr.org
- Recruiting
Institut Universitaire de Cancer de Toulouse
Toulouse
Laurence Gladieff, gladieff.laurence@iuct-oncopole.fr
- Recruiting
Institute Gustave Roussy
Villejuif
Alexandra Leary, MD PhD, alexandra.LEARY@gustaveroussy.fr
Belgium6 sites, 6 recruiting
- Recruiting
Antwerp University Hospital
Antwerp
Laure-Anne Teuwen, laure-anne.teuwen@uza.be
- Recruiting
Clinique Universitaire Saint-Luc
Brussels
Jean-Francois Baurain, jean-francois.baurain@saintluc.uclouvain.be
- Recruiting
GHDC
Charleroi
Sarah Lefèvre, sarah.lefevre@ghdc.be
- Recruiting
CHU Helora
Mons
Nathalie Cornez, nathalie.cornez@helora.be
- Recruiting
CHU UCL Namur
Namur
Stéphanie Henry, stephanie.henry@chuuclnamur.uc
- Recruiting
AZ Damiaan
Ostend
Isabelle Spoormans, isabelle.spoormans@azoostende.be
Czechia4 sites, 4 recruiting
- Recruiting
Fakultní nemocnice Hradec Králové
Hradec Králové
Ivan Praznovec, ivan.praznovec@fnhk.cz
- Recruiting
FN Bulovka
Prague
Michal Zikan, michal.zikan@bulovka.cz
- Recruiting
FN Motol
Prague
Anna Nohejlova, anna.nohejlova@fnmotol.cz
- Recruiting
Všeobecná fakultní nemocnice v Praze
Prague
Roman Kocian, roman.kocian@vfn.cz
Italy1 site, 1 recruiting
- Recruiting
Policlinico Universitario Fondazione Agostino Gemelli
Roma
Francesco Fanfani, francesco.fanfani@policlinicogemelli.it
About this study
Official title: RAINBO: Refining Adjuvant Treatment IN Endometrial Cancer Based On Molecular Features, TransPORTEC Platform Trials - MMRd-GREEN.
RAINBO MMRd-GREEN 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.
Read the detailed description
The MMRd-GREEN trial (NCT05255653) 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.
There are three other RAINBO trials, which are registered separately:
The p53abn-RED trial (NCT06712472) is an international, multicenter, phase III randomised trial wherein patients with completely resected invasive stage I-III p5abn endometrial cancer and treated with adjuvant chemoradiation will be randomized between olaparib for one year and observation.
The NSMP-ORANGE trial (NCT07831902) is an international, multicenter, non-inferiority phase III randomised trial wherein patients with stage II (with substantial LVSI) or stage III no-specific molecular profile (NSMP) endometrial cancer are randomised between standard chemoradiation and external beam radiotherapy followed by oral progestin for two years.
The POLEmut-BLUE trial (NCT05640999) is an international, multicenter, single arm, phase II trial wherein safety of de-escalation of adjuvant therapy in POLE-mutated endometrial cancer is investigated.
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.
- Conditions
- Endometrial Cancer
- Being tested
- Pelvic external beam radiotherapy, Chemotherapy, Durvalumab, Vaginal brachytherapy
- Keywords
- Endometrial Cancer, Molecular risk factors, Durvalumab, Chemotherapy, Radiotherapy, MMRd
- Medical subject headings
- Endometrial Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pelvic external beam radiotherapyRadiation
Also called EBRT
45.0-48.6 Gy; 1.8-2.0 Gy per fraction, 5 fractions a week
ChemotherapyDrug
Also called Cisplatin, Carboplatin, Paclitaxel
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.
DurvalumabDrug
Also called Imfinzi
1500 mg intravenous once every 4 weeks for in total 1 year (13 cycles) starting within the first week of radiotherapy,
Vaginal brachytherapyRadiation
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).
| Study group | Role | What they receive |
|---|---|---|
| MMRd-GREEN trial: experimental | Experimental | Adjuvant radiotherapy combined with and followed by durvalumab, 1500 mg intravenous once every 4 weeks for in total 1 year (13 cycles) Receives: Radiation: Pelvic external beam radiotherapy; Drug: Durvalumab; Radiation: Vaginal brachytherapy |
| MMRd-GREEN trial: control | Active comparator | Adjuvant pelvic external beam radiotherapy +/- chemotherapy Receives: Radiation: Pelvic external beam radiotherapy; Drug: Chemotherapy; Radiation: Vaginal brachytherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recurrence-free survival
RFS is defined as time from randomization until date of any recurrence (local or distant) or date of death due to any cause.
Measured: 3 years
Secondary outcomes (5)
Efficacy endpoints
- Investigator assessed median and 5-year RFS
- Vaginal RFS, pelvic RFS, distant metastasis free-survival (median, 3-year, 5-year)
- Disease-specific survival (median, 3-year, 5-year)
- Overall Survival (OS) (median, 3 year, 5 year): will be determined from the date of randomization to the date of death from any cause. Subjects who have not died at the time of data freeze for the final analysis will be censored at the date the patient was last known to be alive.
Measured: 5 years
Quality of Life Endpoints
Quality of life analysis using the EORTC QLQC30 and QLQEN24.
Measured: 5 years
Safety and tolerability endpoints.
Safety and tolerability endpoints will consist of the evaluation of side-effects according to the NCI-CTCAE version 5, AEs, withdrawals due to AEs, dose interruptions.
Measured: 3 years, 5 years
Biomarker
PD-L1 expression assessment using the SP263 immunohistochemistry assay (thresholds: ≥1% and ≥5%)
Measured: Baseline
Exploratory translational research
Exploratory translational research:
- MMRd-GREEN specific:
- Evaluation of antigen presentation status (e.g. JAK1/2 and B2M mutational status)
Measured: 3 years, 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2022
- Study start11 Nov 2021
- Primary completion1 Jan 2030 (estimated)
- Study completion1 Jan 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Endometrial CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Platform trial wherein eligible patients are assigned to one of four parallel running clinical trials. Here, the MMRd-GREEN trial is registered. The MMRd GREEN trial has a superiority design.
- Masking
- None (open label)
- Enrolment
- 316 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Leiden University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Dutch Gynaecological Oncology Group, Cancer Research UK & UCL Cancer Trials Centre, Dutch Cancer Society, AstraZeneca, National Cancer Institute, France, Canadian Institutes of Health Research (CIHR), BGOG: Belgian Gynaelogical Onology Group, Belgium, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Institute Gustave Roussy Paris, Central & Eastern European Gynecologic Oncology Group (CEEGOG), Canadian Cancer Trials Group (CCTG)
- Responsible party
- Principal investigator, J.R. Kroep, Leiden University Medical Center
- Investigators
- Judith R Kroep, MD PhD, Principal investigator, Medical Oncology, Leiden University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05255653
- Sponsor's protocol ID
- RAINBO-GREEN
- Other IDs
- ENGOT-en14
- Acronym
- RAINBO-GREEN
- Status last verified
- Oct 2026
- First submitted
- 1 Feb 2022
- Last updated
- 8 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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
RAINBO 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.
PubMed 36600534Secord 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.
PubMed 40966692