NCT05255653

Refining Adjuvant Treatment IN Endometrial Cancer Based On Molecular Features

Refining Adjuvant Treatment IN Endometrial Cancer Based On Molecular Features: the p53abn-RED Trial, the MMRd-GREEN Trial, the NSMP-ORANGE Trial and the POLEmut-BLUE Trial

• Status: Recruiting
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 1,615 (estimated)
• Sponsor: Leiden University Medical Center · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Endometrial Cancer

Interventions

Type	Name	Description
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

Timeline

• Start date: 2021-11-11
• Primary completion: 2030-01-01
• Completion: 2031-01-01
• First posted: 2022-02-24
• Last updated: 2024-11-29

Locations

14 sites across 4 countries: Canada, France, Netherlands, United Kingdom