Genetic-Based Adjuvant Therapy for Endometrial Cancer

Recruiting at 98 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach to treating early-stage endometrial cancer, which affects the womb's lining, in patients with specific genetic markers. It seeks to determine if less intensive follow-up treatments are effective for individuals with either POLE-mutated cancer or certain other non-aggressive cancer profiles. Participants will join different study groups that involve monitoring, and some may receive additional treatments such as vaginal brachytherapy (internal radiation therapy) or adjuvant radiotherapy (external beam radiation therapy, with or without brachytherapy). Candidates include those who have undergone surgery to remove their uterus and ovaries and have no remaining visible cancer. This trial aims to help researchers understand if some patients can safely receive less aggressive follow-up care. As a Phase 2 trial, it measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important research.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that vaginal brachytherapy, a type of internal radiation for early-stage endometrial cancer, is generally safe. Studies indicate it effectively controls the disease with few side effects. The PORTEC-2 trial, a large study, found that this treatment had good results with a low risk of harmful effects.

For additional radiation therapy, research suggests it is usually well-tolerated. However, some studies indicate it might slightly increase the risk of other cancers, such as non-Hodgkin lymphoma. While it effectively controls cancer in the pelvic area, there are some risks to consider.

Overall, these treatments have been safely used in many patients, but discussing any concerns with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for endometrial cancer because they explore personalized approaches by looking at genetic factors. Unlike the standard care that typically involves surgery, chemotherapy, or radiation, these trials focus on observation, potentially combined with vaginal brachytherapy or adjuvant radiotherapy, depending on genetic markers. This could lead to more tailored treatments, minimizing unnecessary interventions and possibly reducing side effects. By focusing on genetic-based adjuvant therapy, the trials aim to refine treatment plans for better outcomes and improved quality of life for patients.

What evidence suggests that this trial's treatments could be effective for early-stage endometrial cancer?

Research has shown that vaginal brachytherapy, a type of targeted radiation treatment, provides excellent control of early-stage endometrial cancer with few side effects. Studies have found that shorter, higher-dose sessions of vaginal brachytherapy are as effective as longer, lower-dose ones. In this trial, some participants will receive vaginal brachytherapy, while others may receive adjuvant radiotherapy, which combines external beam radiation therapy with brachytherapy. This combination significantly improves the chances of remaining cancer-free, with patients having a 90% chance of being cancer-free five years later. This evidence supports the potential effectiveness of these treatments in managing endometrial cancer. ^{2 6 7 8 9}

Who Is on the 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

Are You a Good Fit for This Trial?

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 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.

Patients must be accessible for treatment and follow-up at the participating centre

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10629328/

Effects of Adjuvant Radiation Plus Chemotherapy on ... Stage IIIC patients treated with chemotherapy plus radiation exhibited a significantly reduced risk for death from endometrial cancer in both ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1048891X24002755

Impact of different adjuvant radiotherapy modalities on ... The progression-free survival rates at 5 years were 90.0% (95% CI, 82.2 to 94.6) in the external beam radiation therapy combined with vaginal brachytherapy ...

3. ascopubs.org ascopubs.org/doi/10.1200/jco.2007.25.18_suppl.5504

Adjuvant external beam radiotherapy (EBRT) in the ... 92% patients in EBRT arm received immediate treatment, 90% receiving all protocol specified treatment. 2% patients in no EBRT arm received ...

4. practicalradonc.org practicalradonc.org/article/S1879-8500(22)00273-9/fulltext

Radiation Therapy for Endometrial Cancer: An American ... With the results of several recently published clinical trials, this guideline informs on the use of adjuvant radiation therapy (RT) and ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa1813181

Adjuvant Chemotherapy plus Radiation for Locally ... Chemotherapy plus radiation was not associated with longer relapse-free survival than chemotherapy alone in patients with stage III or IVA endometrial ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6662191/

National trends, outcomes, and costs of radiation therapy in ... In conclusion, our results showed that adjuvant radiotherapy was associated with improved survival outcomes in women with HIR endometrial cancer, with no ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1048891X24076801

Adjuvant Chemotherapy With External Beam Radiation ... The 5-year DFS/OS rates were 56%/68% for those who received both chemotherapy and EBRT. Among patients treated with adjuvant EBRT, pelvic control was 93%.

8. nature.com nature.com/articles/s41598-024-74840-4

Association between radiation therapy for primary ... Our findings suggest that adjuvant RT for endometrial cancer patients increases the risk of non-Hodgkin lymphoma and several types of solid cancer.

9. jenci.springeropen.com jenci.springeropen.com/articles/10.1186/s43046-025-00302-1

Comparative efficacy and safety of vaginal brachytherapy ... This review assesses the efficacy and safety of EBRT + VBT versus VBT alone in intermediate- to high-risk endometrial cancer.