What side effects are associated with this type of intervention?

Common treatments for endometrial cancer, including chemotherapy, radiation therapy, and targeted therapies, have various side effects. Chemotherapy can cause nausea, vomiting, fatigue, hair loss, and increased risk of infections. Radiation therapy may lead to skin irritation, fatigue, and gastrointestinal issues such as diarrhea. Targeted therapies, which are more specific to molecular profiles like those in the RAINBO program, can cause side effects such as hypertension, liver toxicity, and gastrointestinal disturbances. Additionally, some targeted therapies may lead to specific organ toxicities depending on the molecular target.

What prior FDA approvals exist?

The FDA has approved several targeted therapies for endometrial cancer, particularly focusing on molecular profiles. Pembrolizumab, an immune checkpoint inhibitor, has been approved for mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) endometrial cancers. Additionally, lenvatinib in combination with pembrolizumab has been approved for advanced endometrial cancer that is not MSI-H or dMMR. These approvals align with the molecularly targeted approach being studied in the RAINBO umbrella program, which investigates adjuvant therapies based on specific molecular profiles such as p53 abnormalities, mismatch repair deficiencies, and POLE mutations.

What other types of research exist?

Promising novel alternatives for endometrial cancer treatment in 2024 include the use of PARP inhibitors like niraparib for tumors with homologous recombination deficiency (HRD) and BRCA mutations, as well as angiogenesis inhibitors such as bevacizumab. Additionally, immunotherapy agents targeting specific molecular profiles and combination therapies involving targeted agents and chemotherapy are also being explored.

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Adjuvant Therapy for Endometrial Cancer (RAINBO Trial)

Phase 2 & 3

Recruiting

Led By Alexandra Leary, Md PhD

Research Sponsored by Leiden University Medical Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Underwent hysterectomy and bilateral salpingo-oophorectomy without macroscopic residual disease

WHO performance status 0, 1 or 2

Must not have

History of another primary malignancy within the past 5 years

Prior pelvic radiation

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 3 years, 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests new treatments for endometrial cancer based on the cancer's genetic makeup. Patients are grouped by their cancer type and given tailored treatments combining radiation, chemotherapy, and targeted drugs. The aim is to find the most effective and least harmful treatments for each specific type of endometrial cancer. Dostarlimab has shown promising results in treating endometrial cancer, with a trial curing 100% of CRC patients without severe adverse events.

Who is the study for?

This trial is for patients with endometrial cancer, categorized by their cancer's molecular profile. They must have a WHO performance status of 0-2, weigh over 30 kg, and have no distant metastases or major surgeries within the last 28 days. Patients should not have had prior treatments that conflict with the trial drugs and must be able to follow up for treatment.

What is being tested?

The RAINBO program includes four trials testing new adjuvant therapies in endometrial cancer based on molecular profiles: p53abn-RED for p53 abnormal cancers; MMRd-GREEN for mismatch repair deficient; NSMP-ORANGE when there's no specific profile; POLEmut-BLUE for POLE mutant cancers.

What are the potential side effects?

Potential side effects may include reactions related to chemotherapy, immunotherapy (like Durvalumab), hormonal therapy (such as Medroxyprogesterone Acetate), targeted therapy (Olaparib), radiation therapy, and observation-related complications. Specifics depend on each patient's treatment plan.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have had my uterus and both ovaries removed with no visible disease left.

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I can take care of myself but may not be able to do heavy physical work.

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My endometrial cancer diagnosis is confirmed by tissue analysis.

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My cancer has not spread to distant parts of my body.

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I will start treatment within 10 weeks after my surgery.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have had another type of cancer in the last 5 years.

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I have had radiation therapy to my pelvic area before.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 3 years, 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~3 years, 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 3 years, 5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

MMRd-GREEN trial

NSMP-ORANGE trial

POLEmut-BLUE trial

+1 more

Secondary study objectives

Endometrial cancer-specific survival

Health-related quality of life - Assessed using the EORTC QLQ-C30 questionnaire

Health-related quality of life - Assessed using the EORTC QLQ-EN24 questionnaire

+5 more

Side effects data

From 2014 Phase 4 trial • 45 Patients • NCT02000531

29%

Nausea

19%

Leukopenia

14%

Anaemia

14%

Vomiting

14%

Neutropenia

14%

White blood cell count decreased

14%

Thrombocytopenia

14%

Alanine aminotransferase increased

10%

Neutrophil count decreased

10%

Platelet count decreased

10%

Aspartate aminotransferase increased

Musculoskeletal pain

Dizziness

Diarrhea

Back pain

100%

80%

60%

40%

20%

Study treatment Arm

Erlotinib-Chemotherapy

Chemotherapy-Erlotinib

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

8Treatment groups

Experimental Treatment

Active Control

Group I: p53abn-RED trial: experimentalExperimental Treatment4 Interventions

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

Group II: POLEmut-BLUE trial: main cohortExperimental Treatment1 Intervention

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 III: POLEmut-BLUE trial: exploratory cohortExperimental Treatment3 Interventions

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 IV: NSMP-ORANGE trial: experimentalExperimental Treatment4 Interventions

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

Group V: MMRd-GREEN trial: experimentalExperimental Treatment3 Interventions

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

Group VI: MMRd-GREEN trial: controlActive Control3 Interventions

Adjuvant pelvic external beam radiotherapy +/- chemotherapy

Group VII: NSMP-ORANGE trial: controlActive Control3 Interventions

Adjuvant radiotherapy and chemotherapy

Group VIII: p53abn-RED trial: controlActive Control3 Interventions

Adjuvant radiotherapy and chemotherapy

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Megestrol Acetate

2007

Completed Phase 3

~540

Durvalumab

2017

Completed Phase 2

~3750

Chemotherapy

2003

Completed Phase 4

~3050

Medroxyprogesterone Acetate

2015

Completed Phase 3

~600

Olaparib

2007

Completed Phase 4

~2190

0 / 7Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for endometrial cancer, particularly those studied in the RAINBO umbrella program, involve molecularly targeted therapies. These treatments work by targeting specific genetic and molecular abnormalities within the cancer cells. For example, therapies for p53 abnormal endometrial cancer aim to restore normal p53 function or counteract its loss, while treatments for mismatch repair deficient cancers focus on enhancing the immune response against the tumor. POLE mutant cancers, which have a high mutation rate, may respond well to immunotherapy. These targeted approaches are significant for patients as they offer more personalized and potentially more effective treatment options, improving outcomes and reducing unnecessary side effects.

Dasatinib, paclitaxel, and carboplatin in women with advanced-stage or recurrent endometrial cancer: A pilot clinical and translational study.Disparity between Inter-Patient Molecular Heterogeneity and Repertoires of Target Drugs Used for Different Types of Cancer in Clinical Oncology.Efficacy of afatinib in a HER2 amplification-positive endometrioid adenocarcinoma patient- a case report.