Refining Adjuvant Treatment IN Endometrial Cancer Based On Molecular Features

Trial statusRecruiting
Trial phasePhase 2, Phase 3
Trial typeInterventional
Biological sexFemale
Age18+
SponsorLeiden University Medical Center

About this trial

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

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

None

Disqualifiers

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)

Trial design

Design model

Parallel

Treatments tested in this trial

  • 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 intervention

    No adjuvant therapy

Treatment groups

1,615 Participants
are divided into 8 treatment groups

8

Treatment groups

See each treatment group below.

Group A: p53abn-RED trial: experimentalExperimental treatment 4 interventions
Group B: p53abn-RED trial: controlActive comparator 3 interventions
Group C: MMRd-GREEN trial: experimentalExperimental treatment 3 interventions
Group D: MMRd-GREEN trial: controlActive comparator 3 interventions
Group E: NSMP-ORANGE trial: experimentalExperimental treatment 4 interventions
Group F: NSMP-ORANGE trial: controlActive comparator 3 interventions
Group G: POLEmut-BLUE trial: main cohortOther 1 intervention
Group H: POLEmut-BLUE trial: exploratory cohortOther 3 interventions

Trial outcomes

Primary outcomes

1

p53abn-RED trial

Recurrence-free survival

Time frame
3 years
2

MMRd-GREEN trial

Recurrence-free survival

Time frame
3 years
3

NSMP-ORANGE trial

Recurrence-free survival

Time frame
3 years
4

POLEmut-BLUE trial

Pelvic recurrence-free survival

Time frame
3 years

Secondary outcomes

1

Recurrence-free survival

All RAINBO trials

Time frame
5 years
2

Pelvic recurrence-free survival

All RAINBO trials

Time frame
5 years
3

Vaginal recurrence-free survival

All RAINBO trials

Time frame
3 years, 5 years
4

Endometrial cancer-specific survival

All RAINBO trials

Time frame
3 years, 5 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Leiden University Medical Center

Lead sponsor

Institute Gustave Roussy (sponsor p53abn-RED trial)

Collaborator

Leiden University Medical center (sponsor MMRd-GREEN trial)

Collaborator

University College London (sponsor NSMP-ORANGE trial)

Collaborator

Canadian Clinical Trials Group (sponsor POLEmut-BLUE trial)

Collaborator

Dutch Gynaecological Oncology Group

Collaborator

Comprehensive Cancer Centre The Netherlands

Collaborator

Cancer Research UK & UCL Cancer Trials Centre

Collaborator

Dutch Cancer Society

Collaborator

AstraZeneca

Collaborator

National Cancer Institute, France

Collaborator

Canadian Institutes of Health Research (CIHR)

Collaborator