Refining Adjuvant Treatment IN Endometrial Cancer Based On Molecular Features

Sponsor
Leiden University Medical Center
Study ID
NCT05255653
Phase
PHASE2/PHASE3
Status
Recruiting
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Conditions

Eligibility Criteria

Sex
FEMALE
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Olaparib — DRUG
    300 mg twice daily for one year
  • Pelvic external beam radiotherapy — RADIATION
    45.0-48.6 Gy; 1.8-2.0 Gy per fraction, 5 fractions a week
  • Chemotherapy — 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.
  • Durvalumab — DRUG
    1500 mg intravenous once every 4 weeks for in total 1 year (13 cycles) starting within the first week of radiotherapy,
  • Medroxyprogesterone Acetate — DRUG
    Oral medroxyprogesterone acetate for two years
  • Megestrol Acetate — DRUG
    Oral medroxyprogesterone acetate for two years
  • Vaginal brachytherapy — 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 — OTHER
    No adjuvant therapy

Study Details

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

Key Dates

Start date
Nov 11, 2021
Status verified
May 2026
Primary completion
Jan 1, 2030
Completion
Jan 1, 2031

Study Design

Enrollment
1,615 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: p53abn-RED trial: experimental
    Adjuvant radiotherapy and chemotherapy followed by olaparib (lynparza), 300 mg twice daily, for one year
  • Active Comparator: p53abn-RED trial: control
    Adjuvant radiotherapy and chemotherapy
  • Experimental: 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)
  • Active Comparator: MMRd-GREEN trial: control
    Adjuvant pelvic external beam radiotherapy +/- chemotherapy
  • Experimental: NSMP-ORANGE trial: experimental
    Adjuvant radiotherapy followed by oral progestagens (medroxyprogesterone acetate or megestrol acetate) for two years
  • Active Comparator: NSMP-ORANGE trial: control
    Adjuvant radiotherapy and chemotherapy
  • Other: 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
  • Other: 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

Primary Outcome Measure

p53abn-RED trial [ Time Frame: 3 years ]

Central Contacts

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