Genetic-Based Adjuvant Therapy for Endometrial Cancer

Recruiting at 67 trial locations

Overseen By Wendy Parulekar

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Canadian Cancer Trials Group

Disqualifiers: Prior chemotherapy, Prior radiation, Other malignancies, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6-8 weeks

393 Participants Needed

Trial Summary

What is the purpose of this trial?

This protocol tests de-escalated adjuvant treatment in patients with POLE-mutated or p53wt/NSMP (p53 wildtype/no specific molecular profile) early-stage endometrial cancer (EC). Patients may be enrolled in one of two sub-studies * EN10.A/RAINBO BLUE: POLE-mutated EC * EN10.B/TAPER: p53 wildtype / NSMP EC

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Genetic-Based Adjuvant Therapy for Endometrial Cancer?

Recent studies have shown that using molecular profiling to guide adjuvant therapy in endometrial cancer can improve risk assessment and treatment outcomes. Specifically, adjuvant vaginal brachytherapy is recommended for high-intermediate risk endometrial cancer to enhance local control with minimal side effects, and pelvic radiotherapy is supported for high-risk cases to improve survival rates. ^{1 2 3 4 5}

How does the observation treatment for endometrial cancer differ from other treatments?

The observation treatment for endometrial cancer, also known as watchful waiting or active surveillance, is unique because it involves closely monitoring the patient without immediate intervention, unlike other treatments that may involve surgery, chemotherapy, or radiotherapy. This approach is typically considered for patients with low-risk disease where the cancer is not expected to progress quickly, allowing for a less invasive management strategy. ^{1 3 6 7 8}

Research Team

Kathy Han

Principal Investigator

University Health Network, Princess Margaret Hospital, Toronto ON Canada

Jessica McAlpine

Principal Investigator

BCCA-Vancouver Cancer Centre, Vancouver BC Canada

Eligibility Criteria

This trial is for adults with early-stage endometrial cancer that's either POLE-mutated or p53 wildtype/NSMP. Participants must have had a hysterectomy, no remaining visible disease, and an ECOG performance status of 0-2. They should be able to complete questionnaires in English, French or another validated language and start treatment within 10 weeks post-surgery.

Inclusion Criteria

I am 18 years old or older.

I had surgery to remove my uterus and ovaries with no visible cancer left.

I can care for myself and am up and about more than 50% of my waking hours.

Exclusion Criteria

Clinical evidence of distant metastasis as determined by imaging

I have had cancer before, but it was either skin cancer treated successfully, cervical cancer treated without spreading, or any cancer treated over 5 years ago with no current signs of disease.

I have had chemotherapy before surgery for my current endometrial cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tailored adjuvant therapy, which may include observation, vaginal brachytherapy, or adjuvant radiotherapy depending on the sub-study

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Treatment Details

Interventions

• Adjuvant radiotherapy (EBRT +/- brachytherapy)
• Observation
• Vaginal brachytherapy

Trial Overview The study examines de-escalated adjuvant treatments in two sub-studies: RAINBO BLUE for POLE-mutated cancer and TAPER for p53 wildtype/NSMP cancer. It compares the effects of adjuvant radiotherapy (with or without brachytherapy), vaginal brachytherapy alone, or just observation after surgery.

Participant Groups

Group I: Sub-study A: RAINBO BLUE Cohort A1 Experimental Treatment 1 Intervention

Observation

Group II: Sub-Study B: TAPER Experimental Treatment 2 Interventions

Observation or Vaginal Brachytherapy

Group III: Sub-Study A: RAINBO BLUE Cohort A2 Experimental Treatment 2 Interventions

Observation or Adjuvant Radiotherapy

Who Is Running the Clinical Trial?

Canadian Cancer Trials Group

Lead Sponsor

Trials

135

Recruited

70,300+

Canadian Cancer Clinical Trials Network

Collaborator

Trials

2

Recruited

530+

Findings from Research

The integration of genomic characterization from the Cancer Genome Atlas has led to the identification of four distinct endometrial cancer subgroups, which can improve prognostic assessments and treatment decisions.

Current research is investigating the clinical utility of molecular profiling to tailor adjuvant therapy specifically for patients in the high-intermediate-risk group, aiming to reduce both under- and overtreatment in endometrial cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant Treatment Recommendations in Early-Stage Endometrial Cancer: What Changes With the Introduction of The Integrated Molecular-Based Risk Assessment. Nero, C., Ciccarone, F., Pietragalla, A., et al.[2021]

A study of 947 early-stage endometrial carcinoma patients confirmed four distinct molecular subgroups (p53-mutant, MSI, POLE-mutant, and NSMP), which can help in predicting patient outcomes and guiding treatment decisions.

Integrating molecular and clinicopathologic factors into risk assessments significantly enhances prognostic accuracy, potentially reducing the chances of overtreatment or undertreatment in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved Risk Assessment by Integrating Molecular and Clinicopathological Factors in Early-stage Endometrial Cancer-Combined Analysis of the PORTEC Cohorts. Stelloo, E., Nout, RA., Osse, EM., et al.[2020]

Adjuvant treatment for endometrial cancer varies based on risk factors, with low-risk patients typically managed with surgery alone, while high-intermediate risk patients benefit from vaginal brachytherapy, which has mild side effects and does not affect quality of life.

Recent studies have identified four molecular sub-types of endometrial cancer that provide better prognostic information than traditional histo-pathological characteristics, paving the way for more personalized and effective treatment strategies based on molecular profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant therapy for endometrial cancer in the era of molecular classification: radiotherapy, chemoradiation and novel targets for therapy. van den Heerik, ASVM., Horeweg, N., de Boer, SM., et al.[2022]

Comprehensive genomic profiling (CGP) successfully classified recurrent endometrial cancer into the four Cancer Genome Atlas (TCGA) categories, helping to identify specific genomic alterations that can guide treatment decisions.

In this study of 74 patients, 32% received targeted therapies based on CGP results, with a clinical benefit rate of 62.5%, indicating that CGP can effectively inform personalized treatment strategies in routine clinical care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive genomic profiling of recurrent endometrial cancer: Implications for selection of systemic therapy. Prendergast, EN., Holman, LL., Liu, AY., et al.[2020]

Endometrial cancer, the most common gynecologic cancer in the U.S., is seeing rising death rates, but recent advancements in precision medicine, including the FDA approval of pembrolizumab for tumors with defective DNA mismatch repair, offer new hope for 20-30% of advanced cases.

Current research is focused on identifying effective biomarkers for targeted therapies, as single-agent treatments have shown only modest efficacy, and future clinical trials will explore novel combinations and the use of advanced genomic data to improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endometrial cancer: Molecular markers and management of advanced stage disease. Arend, RC., Jones, BA., Martinez, A., et al.[2020]

For patients with intermediate and high-intermediate risk endometrial cancer, traditional adjuvant treatments like vaginal cuff brachytherapy and pelvic external beam radiotherapy reduce local and pelvic recurrence rates but do not improve overall survival or distant metastasis rates, and they can lead to increased morbidity and decreased quality of life.

Emerging strategies that incorporate molecular profiles from genomic analyses, such as those from The Cancer Genome Atlas, aim to personalize treatment and potentially allow for therapeutic de-escalation in about half of high-intermediate risk patients, although more prospective data is needed to validate these approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Molecular-integrated risk profile: An opportunity for therapeutic de-escalation in intermediate and high-intermediate risk endometrial cancer]. Espenel, S., Pointreau, Y., Genestie, C., et al.[2022]

Recent research has identified four distinct molecular subclasses of endometrial cancer (EC) that have different prognoses, which could help tailor adjuvant treatment for patients.

Combining molecular and clinicopathological risk factors may enhance treatment selection for women with high-intermediate risk EC, but current treatment guidelines have not yet incorporated these molecular assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selecting Adjuvant Treatment for Endometrial Carcinoma Using Molecular Risk Factors. Wortman, BG., Nout, RA., Bosse, T., et al.[2023]

Liquid biopsy analyses, including the study of plasma cfDNA/ctDNA and uterine aspirate, can provide valuable insights into tumor evolution and heterogeneity in endometrial cancer patients, potentially guiding more effective treatment options.

In a case report of a microsatellite instability endometrial cancer patient, these analyses revealed rapid disease progression post-surgery, highlighting the need for improved monitoring tools and new therapeutic strategies beyond the standard carboplatin and paclitaxel regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving the Management of Endometrial Cancer Patients through the Use of Liquid Biopsy Analyses: A Case Report. Casas-Arozamena, C., Cortegoso, A., Piñeiro-Perez, R., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Adjuvant Treatment Recommendations in Early-Stage Endometrial Cancer: What Changes With the Introduction of The Integrated Molecular-Based Risk Assessment. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Improved Risk Assessment by Integrating Molecular and Clinicopathological Factors in Early-stage Endometrial Cancer-Combined Analysis of the PORTEC Cohorts. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Adjuvant therapy for endometrial cancer in the era of molecular classification: radiotherapy, chemoradiation and novel targets for therapy. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Comprehensive genomic profiling of recurrent endometrial cancer: Implications for selection of systemic therapy. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Endometrial cancer: Molecular markers and management of advanced stage disease. [2020]

6. France pubmed.ncbi.nlm.nih.gov

[Molecular-integrated risk profile: An opportunity for therapeutic de-escalation in intermediate and high-intermediate risk endometrial cancer]. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Selecting Adjuvant Treatment for Endometrial Carcinoma Using Molecular Risk Factors. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Improving the Management of Endometrial Cancer Patients through the Use of Liquid Biopsy Analyses: A Case Report. [2022]