Refining Adjuvant Treatment in Endometrial Cancer Based on Molecular Features

NCT ID: NCT05255653

Last Updated: 2024-11-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2/PHASE3

Total Enrollment

1615 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-11-11

Study Completion Date

2031-01-01

Brief Summary

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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

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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.

Conditions

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Endometrial Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Platform trial wherein eligible patients are assigned to one of four parallel running clinical trials. Three of four trials are randomised controlled trials and one is a prospective clinical trial with two study arms.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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p53abn-RED trial: experimental

Adjuvant radiotherapy and chemotherapy followed by olaparib (lynparza), 300 mg twice daily, for one year

Group Type EXPERIMENTAL

Olaparib

Intervention Type DRUG

300 mg twice daily for one year

Pelvic external beam radiotherapy

Intervention Type RADIATION

45.0-48.6 Gy; 1.8-2.0 Gy per fraction, 5 fractions a week

Chemotherapy

Intervention Type DRUG

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.

Vaginal brachytherapy

Intervention Type RADIATION

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).

p53abn-RED trial: control

Adjuvant radiotherapy and chemotherapy

Group Type ACTIVE_COMPARATOR

Pelvic external beam radiotherapy

Intervention Type RADIATION

45.0-48.6 Gy; 1.8-2.0 Gy per fraction, 5 fractions a week

Chemotherapy

Intervention Type DRUG

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.

Vaginal brachytherapy

Intervention Type RADIATION

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).

MMRd-GREEN trial: experimental

Adjuvant radiotherapy combined with and followed by durvalumab, 1500 mg intravenous once every 4 weeks for in total 1 year (13 cycles)

Group Type EXPERIMENTAL

Pelvic external beam radiotherapy

Intervention Type RADIATION

45.0-48.6 Gy; 1.8-2.0 Gy per fraction, 5 fractions a week

Durvalumab

Intervention Type DRUG

1500 mg intravenous once every 4 weeks for in total 1 year (13 cycles) starting within the first week of radiotherapy,

Vaginal brachytherapy

Intervention Type RADIATION

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).

MMRd-GREEN trial: control

Adjuvant pelvic external beam radiotherapy +/- chemotherapy

Group Type ACTIVE_COMPARATOR

Pelvic external beam radiotherapy

Intervention Type RADIATION

45.0-48.6 Gy; 1.8-2.0 Gy per fraction, 5 fractions a week

Chemotherapy

Intervention Type DRUG

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.

Vaginal brachytherapy

Intervention Type RADIATION

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).

NSMP-ORANGE trial: experimental

Adjuvant radiotherapy followed by oral progestagens (medroxyprogesterone acetate or megestrol acetate) for two years

Group Type EXPERIMENTAL

Pelvic external beam radiotherapy

Intervention Type RADIATION

45.0-48.6 Gy; 1.8-2.0 Gy per fraction, 5 fractions a week

Medroxyprogesterone Acetate

Intervention Type DRUG

Oral medroxyprogesterone acetate for two years

Megestrol Acetate

Intervention Type DRUG

Oral medroxyprogesterone acetate for two years

Vaginal brachytherapy

Intervention Type RADIATION

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).

NSMP-ORANGE trial: control

Adjuvant radiotherapy and chemotherapy

Group Type ACTIVE_COMPARATOR

Pelvic external beam radiotherapy

Intervention Type RADIATION

45.0-48.6 Gy; 1.8-2.0 Gy per fraction, 5 fractions a week

Chemotherapy

Intervention Type DRUG

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.

Vaginal brachytherapy

Intervention Type RADIATION

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).

POLEmut-BLUE trial: main cohort

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

Group Type OTHER

Observation

Intervention Type OTHER

No adjuvant therapy

POLEmut-BLUE trial: exploratory cohort

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

Group Type OTHER

Pelvic external beam radiotherapy

Intervention Type RADIATION

45.0-48.6 Gy; 1.8-2.0 Gy per fraction, 5 fractions a week

Vaginal brachytherapy

Intervention Type RADIATION

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).

Observation

Intervention Type OTHER

No adjuvant therapy

Interventions

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Olaparib

300 mg twice daily for one year

Intervention Type DRUG

Pelvic external beam radiotherapy

45.0-48.6 Gy; 1.8-2.0 Gy per fraction, 5 fractions a week

Intervention Type RADIATION

Chemotherapy

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.

Intervention Type DRUG

Durvalumab

1500 mg intravenous once every 4 weeks for in total 1 year (13 cycles) starting within the first week of radiotherapy,

Intervention Type DRUG

Medroxyprogesterone Acetate

Oral medroxyprogesterone acetate for two years

Intervention Type DRUG

Megestrol Acetate

Oral medroxyprogesterone acetate for two years

Intervention Type DRUG

Vaginal brachytherapy

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).

Intervention Type RADIATION

Observation

No adjuvant therapy

Intervention Type OTHER

Other Intervention Names

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Lynparza EBRT Cisplatin Carboplatin Paclitaxel Imfinzi Progestogen Progestogen

Eligibility Criteria

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Inclusion Criteria

* 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.


* p53 abnormal EC
* Histologically confirmed stage I (with invasion) II or III EC
* WHO Performance score 0-1
* 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, AND ALT (SGPT) and/or AST (SGOT) ≤2.5 x ULN


* Mismatch repair deficient EC
* Histologically confirmed (FIGO 2009) stage IB/II EC with myometrial or cervical stroma involvement and lympovascular space invasion (LVSI) OR Stage III EC OR Stage IVA with limited pelvic peritoneal involvement
* WHO Performance score 0-1
* 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.\>\> AND ALT (SGPT) and/or AST (SGOT) ≤2.5 x ULN


* NSMP EC
* Histologically confirmed stage II EC with substantial LVSI or stage III EC
* ER positive EC
* WHO performance status 0-1


* Pathogenic POLE mutation(s)
* For the main cohort, patients must have one of the following combinations of FIGO stage, grade, and LVSI:

* 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
* For the exploratory cohort, patients must have one of the following combinations of FIGO stage, grade, and LVSI:

* stage IA (not confined to polyp), grade 3 - Stage III not included in main cohort
* Multiple molecular classifiers stage IA (not confined to polyp), grade 3 - Stage III
* Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrolment in the trial to document their willingness to participate. A similar process must be followed for sites outside of Canada as per their respective cooperative group's procedures.
* Patient is able (i.e., sufficiently fluent) and willing to complete the QOL and/or health utility questionnaires in either English, French or a validated language. The baseline assessment must be completed within the required timelines, prior to enrolment. Inability (lack of comprehension in English or French, or other equivalent reason such as cognitive issues or lack of competency) to complete the questionnaires will not make the patient ineligible for the study. However, ability but unwillingness to complete the questionnaires will make the patient ineligible.
* Patients must be accessible for treatment and follow up. Patients enrolled on this trial must be treated and followed at the participating center. Investigators must assure themselves the patients enrolled on this trial will be available for complete documentation of the treatment, adverse events, and follow-up.
* Patients must agree to return to their primary care facility for any adverse events which may occur through the course of the trial.
* In accordance with CCTG policy, protocol treatment is to begin within 10 weeks of hysterectomy/bilateral salpingo-oophorectomy.

Exclusion Criteria

* History of another primary malignancy, except for non-melanoma skin cancer, in the past 5 years
* Prior pelvic radiation

The p53abn-RED trial


* Pathogenic POLE mutation(s)
* Mismatch repair deficiency
* Major surgical procedure (as defined by the investigator) within 28 days prior to the first dose of the IP
* 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
* Any previous treatment with a PARP inhibitor, including olaparib
* History of active primary immunodeficiency
* History or evidence of hemorrhagic disorders within 6 months prior to randomization
* Patients with myelodysplastic syndrome/acute myeloid leukemia history or with features suggestive of MDS/AML
* Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT)
* 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.
* Concomitant use of known strong CYP3A inhibitors (eg. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks.
* Concomitant use of known strong (eg. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
* Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
* 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.

The MMRd-GREEN trial


* Pathogenic POLE mutation(s)
* 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.
* 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.

The NSMP-ORANGE trial


* Pathogenic POLE mutation(s)
* Mismatch repair deficiency
* p53 abnormality

The POLEmut-BLUE trial


* Prior chemotherapy for EC
* Isolated tumor cells identified in lymph node(s) for main study cohort (patient can be included in exploratory cohort)
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Institute Gustave Roussy (sponsor p53abn-RED trial)

UNKNOWN

Sponsor Role collaborator

Leiden University Medical center (sponsor MMRd-GREEN trial)

UNKNOWN

Sponsor Role collaborator

University College London (sponsor NSMP-ORANGE trial)

UNKNOWN

Sponsor Role collaborator

Canadian Clinical Trials Group (sponsor POLEmut-BLUE trial)

UNKNOWN

Sponsor Role collaborator

Dutch Gynaecological Oncology Group

OTHER

Sponsor Role collaborator

Comprehensive Cancer Centre The Netherlands

OTHER

Sponsor Role collaborator

Cancer Research UK & UCL Cancer Trials Centre

OTHER

Sponsor Role collaborator

Dutch Cancer Society

OTHER

Sponsor Role collaborator

AstraZeneca

INDUSTRY

Sponsor Role collaborator

National Cancer Institute, France

OTHER_GOV

Sponsor Role collaborator

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role collaborator

Leiden University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Carien Creutzberg

prof

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Alexandra Leary, Md PhD

Role: PRINCIPAL_INVESTIGATOR

Institute Gustave Roussy, Villejuif, France (p53abn-RED trial)

Judith R Kroep, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Leiden University Medical Center, Leiden, The Netherlands (MMRd-GREEN trial)

Melanie E Powell, Md PhD

Role: PRINCIPAL_INVESTIGATOR

Barts Health NHS Trust, London, United Kingdom (NSMP-ORANGE trial)

Emma J Crosbie, Md PhD

Role: PRINCIPAL_INVESTIGATOR

St Mary's Hospital, Manchester, United Kingdom (NSMP-ORANGE trial)

Kathy Han, Md PhD

Role: PRINCIPAL_INVESTIGATOR

Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada (POLEmut-BLUE trial)

Jessica N McAlpine, Md PhD

Role: PRINCIPAL_INVESTIGATOR

University of British Columbia,Vancouver, Canada (POLEmut-BLUE trial)

Locations

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The POLEmut-BLUE trial: Princess Margaret Cancer Centre, University of Toronto

Toronto, , Canada

Site Status RECRUITING

The POLEmut-BLUE trial: University of British Columbia

Vancouver, , Canada

Site Status RECRUITING

The p53abn-RED trial: Institute Gustave Roussy

Villejuif, , France

Site Status NOT_YET_RECRUITING

Amsterdam University Medical Center

Amsterdam, , Netherlands

Site Status RECRUITING

Amphia Ziekenhuis

Breda, , Netherlands

Site Status RECRUITING

Instituut Verbeeten

Breda, , Netherlands

Site Status RECRUITING

Catharina Ziekenhuis

Eindhoven, , Netherlands

Site Status RECRUITING

Medisch Spectrum Twente

Enschede, , Netherlands

Site Status RECRUITING

Universitair Medisch Centrum Groningen

Groningen, , Netherlands

Site Status RECRUITING

The MMRd-GREEN trial: Leiden University Medical Center

Leiden, , Netherlands

Site Status RECRUITING

Erasmus Medical Center

Rotterdam, , Netherlands

Site Status RECRUITING

Haags Medisch Centrum

The Hague, , Netherlands

Site Status RECRUITING

The NSMP-ORANGE trial: Barts Health NHS Trust

London, , United Kingdom

Site Status NOT_YET_RECRUITING

The NSMP-ORANGE trial: Manchester Academic Health Science Centre, St Mary's Hospita

Manchester, , United Kingdom

Site Status NOT_YET_RECRUITING

Countries

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Canada France Netherlands United Kingdom

Central Contacts

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Carien L Creutzberg, MD PhD

Role: CONTACT

+31 71 52 65539

Nanda Horeweg, MD PhD

Role: CONTACT

+31 71 52 65539

Facility Contacts

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Kathy Han, MD PhD

Role: primary

Jessica N McAlpine, MD PhD

Role: primary

Alexandra Leary, MD PhD

Role: primary

Jasper LA Vleugels, Md PhD

Role: primary

Jasper LA Vleugels, MD PhD

Role: backup

Joan Heijns, MD PhD

Role: primary

Frederieke Koppe

Role: primary

Annemarie Thijs

Role: primary

A Wymenga, MD PhD

Role: primary

Ann KL Reyners, MD PhD

Role: primary

Judith R Kroep, MD PhD

Role: primary

+31 71 526 5095

Merve Kaya, MD

Role: backup

+31 71 529 9661

Ingrid Boere, Md PhD

Role: primary

Mandy Kiderlen, Md PhD

Role: primary

Melanie E Powell, MD PhD

Role: primary

Emma J Crosbie, MD PhD

Role: primary

References

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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

Reference Type BACKGROUND

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.

Reference Type BACKGROUND
PMID: 36600534 (View on PubMed)

Secord 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.

Reference Type DERIVED
PMID: 40966692 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

ENGOT-en14-1,2,3,4

Identifier Type: OTHER

Identifier Source: secondary_id

CCTG EN.10 TAPER arm A POLE

Identifier Type: OTHER

Identifier Source: secondary_id

RAINBO

Identifier Type: -

Identifier Source: org_study_id