Refining Adjuvant Treatment IN Endometrial Cancer Based On Molecular Features

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

Conditions

• Endometrial Cancer

Interventions

DRUG

Olaparib

300 mg twice daily for one year

RADIATION

Pelvic external beam radiotherapy

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

DRUG

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.

DRUG

Durvalumab

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

DRUG

Medroxyprogesterone Acetate

Oral medroxyprogesterone acetate for two years

DRUG

Megestrol Acetate

Oral medroxyprogesterone acetate for two years

RADIATION

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).

OTHER

Observation

No adjuvant therapy

Sponsors & Collaborators

• Institute Gustave Roussy (sponsor p53abn-RED trial)

  collaborator UNKNOWN

• Leiden University Medical center (sponsor MMRd-GREEN trial)

  collaborator UNKNOWN

• University College London (sponsor NSMP-ORANGE trial)

  collaborator UNKNOWN

• Canadian Clinical Trials Group (sponsor POLEmut-BLUE trial)

  collaborator UNKNOWN

• Dutch Gynaecological Oncology Group

  collaborator OTHER

• Comprehensive Cancer Centre The Netherlands

  collaborator OTHER

• Cancer Research UK & UCL Cancer Trials Centre

  collaborator OTHER

• Dutch Cancer Society

  collaborator OTHER

• AstraZeneca

  collaborator INDUSTRY

• National Cancer Institute, France

  collaborator OTHER_GOV

• Canadian Institutes of Health Research (CIHR)

  collaborator OTHER_GOV

• Leiden University Medical Center

  lead OTHER

Principal Investigators

• Alexandra Leary, Md PhD · Institute Gustave Roussy, Villejuif, France (p53abn-RED trial)

• Judith R Kroep, MD PhD · Leiden University Medical Center, Leiden, The Netherlands (MMRd-GREEN trial)

• Melanie E Powell, Md PhD · Barts Health NHS Trust, London, United Kingdom (NSMP-ORANGE trial)

• Emma J Crosbie, Md PhD · St Mary's Hospital, Manchester, United Kingdom (NSMP-ORANGE trial)

• Kathy Han, Md PhD · Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada (POLEmut-BLUE trial)

• Jessica N McAlpine, Md PhD · University of British Columbia,Vancouver, Canada (POLEmut-BLUE trial)

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-11-11

Primary Completion

2030-01-01

Completion

2031-01-01

Countries

• Canada
• France
• Netherlands
• United Kingdom

Study Locations