Pembrolizumab + Radiation for Endometrial Cancer

Recruiting at 310 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: Anti-PD-1, Anti-PD-L1

Disqualifiers: Autoimmune disease, Pneumonitis, Liver disease, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 9

168 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase III trial compares whether the addition of pembrolizumab to radiation therapy is more effective than radiation therapy alone in reducing the risk of cancer coming back (recurrence) in patients with newly diagnosed stage I-II endometrial cancer. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. The addition of pembrolizumab to radiation treatment may be more effective than radiation treatment alone in reducing cancer recurrence.

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

The trial protocol does not specify whether you need to stop taking your current medications. However, it mentions that patients who have received any prohibited medications are excluded, so it's best to discuss your current medications with the trial team.

What data supports the effectiveness of the treatment Pembrolizumab + Radiation for Endometrial Cancer?

Research shows that combining external beam radiation therapy (EBRT) with brachytherapy (a type of internal radiation) can improve survival rates in patients with endometrial cancer, especially when surgery is not an option. This suggests that using these radiation therapies together may be effective in treating endometrial cancer. ^{1 2 3 4 5}

Is the combination of Pembrolizumab and Radiation Therapy safe for humans?

Radiation therapy, including external beam radiation therapy (EBRT) and brachytherapy, has been studied for endometrial cancer and is generally considered safe, though it can cause short-term and long-term side effects, particularly in the gastrointestinal area. The safety of Pembrolizumab (also known as KEYTRUDA) has been evaluated in various conditions, and it is generally safe for human use, but it can have side effects like fatigue and skin reactions. ^{3 6 7 8 9}

How is the treatment of pembrolizumab combined with radiation unique for endometrial cancer?

This treatment is unique because it combines pembrolizumab, an immune therapy that helps the body's immune system attack cancer cells, with radiation therapy, which uses high-energy rays to kill cancer cells. This combination may enhance the immune response against the cancer, potentially leading to better outcomes than using either treatment alone. ^{10 11 12 13 14}

Research Team

Floor Backes

Principal Investigator

NRG Oncology

Eligibility Criteria

This trial is for patients with newly diagnosed stage I-II endometrioid endometrial cancer. They must have had specific imaging, surgery, and show no signs of disease outside the uterus. Eligible participants should not have received prior therapy for their cancer, meet certain health criteria, and be within a set time after initial surgery.

Inclusion Criteria

You need to have had a specific type of imaging that shows no signs of disease outside of the uterus.

My cancer shows signs of high microsatellite instability or lacks certain proteins.

I registered for the trial soon after my initial surgery.

Exclusion Criteria

I have an autoimmune disease that could come back and harm my organs.

I do not have any severe illnesses or social situations that would stop me from following the study's requirements.

I am currently in a clinical trial for endometrial cancer or was in one within the last 4 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Patients undergo pelvic external beam radiation therapy (EBRT) daily for 5-6 weeks and vaginal brachytherapy completed within 7 days after completion of EBRT

5-6 weeks

Daily visits for radiation therapy

Immunotherapy

Patients receive pembrolizumab intravenously every 6 weeks for up to 1 year (9 cycles) in the absence of disease progression or unacceptable toxicity

1 year

Every 6 weeks for pembrolizumab infusion

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Every 3 months for 2 years, then every 6 months for 3 years

Treatment Details

Interventions

• Brachytherapy
• External Beam Radiation Therapy
• Pembrolizumab

Trial Overview The study is testing if adding pembrolizumab (an immunotherapy drug) to usual radiation therapy reduces the risk of cancer recurrence better than radiation alone in early-stage high intermediate risk endometrial cancer.

Participant Groups

Group I: Arm II (EBRT, brachytherapy, pembrolizumab) Experimental Treatment 9 Interventions

Patients undergo EBRT and brachytherapy as in Arm I. Within 7 days prior to the start of radiation therapy, patients also receive pembrolizumab IV over 30 minutes on day 1. Treatment with pembrolizumab repeats every 6 weeks for up to 1 year (9 cycles) in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples and CT scans, MRI scans, or x-ray imaging throughout the trial.

Group II: Arm I (EBRT, brachytherapy) Active Control 8 Interventions

Patients undergo pelvic EBRT daily for 5-6 weeks and vaginal brachytherapy completed within 7 days after completion of EBRT in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples and CT scans, MRI scans, or x-ray imaging throughout the trial.

Brachytherapy is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Brachytherapy for:

• Prostate cancer
• Cervical cancer
• Breast cancer
• Skin cancer
• Esophageal cancer

Approved in European Union as Brachytherapy for:

• Prostate cancer
• Cervical cancer
• Breast cancer
• Skin cancer
• Esophageal cancer
• Brain tumors

Approved in Canada as Brachytherapy for:

• Prostate cancer
• Cervical cancer
• Breast cancer
• Skin cancer
• Esophageal cancer

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

NRG Oncology

Collaborator

Trials

242

Recruited

105,000+

Findings from Research

Postoperative external-beam pelvic radiotherapy (EBRT) increases the risk of death in low-risk endometrial cancer patients, suggesting it should not be used for this group.

For high-risk endometrial cancer, EBRT provides a significant disease-free survival advantage, benefiting about 10% of women, while also reducing the risk of pelvic recurrence across all invasive cancer types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival and recurrent disease after postoperative radiotherapy for early endometrial cancer: systematic review and meta-analysis. Johnson, N., Cornes, P.[2022]

In a study of 79 patients with early-stage endometrial cancer, the addition of pelvic radiotherapy to brachytherapy (EBRT-BT) resulted in a significant increase in acute toxicities, including a 37% rise in Grade 1-3 diarrhea and a 34% increase in lethargy compared to brachytherapy alone.

Despite the increased acute toxicities associated with EBRT-BT, all reported side effects resolved within three months post-treatment, highlighting the importance of patient counseling regarding potential risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant radiotherapy for endometrial cancer--a comparative review of radiotherapy technique with acute toxicity. Koh, YV., Tang, JI., Choo, BA., et al.[2020]

A study of 26 elderly women (median age 83) with endometrial cancer who were not surgical candidates showed that definitive radiation therapy, including external beam radiation and brachytherapy, is a feasible and well-tolerated treatment option.

The treatment resulted in an overall survival rate of 89% at 1 year and 73% at 3 years, with only 8% of patients experiencing late toxicity, indicating a favorable safety profile for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Definitive radiation therapy for endometrial cancer in medically inoperable elderly patients. Wegner, RE., Beriwal, S., Heron, DE., et al.[2010]

High-dose rate electronic brachytherapy (EBT) is a feasible and safe option for postoperative adjuvant radiation therapy in endometrial cancer, with 41 patients treated and no reported recurrences during a median follow-up of 3.8 months.

Adverse events were mostly mild to moderate, with no severe complications in the EBT-only group, indicating a favorable safety profile for this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of electronic brachytherapy to deliver postsurgical adjuvant radiation therapy for endometrial cancer: a retrospective multicenter study. Dooley, WC., Thropay, JP., Schreiber, GJ., et al.[2021]

Pembrolizumab (Keytruda) is approved for treating advanced endometrial carcinoma that is microsatellite instability-high or mismatch repair deficient, specifically for patients whose disease has progressed after previous treatments.

This approval is significant for patients who are not candidates for curative surgery or radiation, providing a new therapeutic option for a challenging stage of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Approved Use for Keytruda. Aschenbrenner, DS.[2022]

In the KEYNOTE-158 study, pembrolizumab showed a clinically meaningful objective response rate in patients with advanced MSI-H/dMMR endometrial cancer, with 84 out of 90 patients completing health-related quality of life (HRQoL) assessments.

Patients receiving pembrolizumab experienced significant improvements in their quality of life, with mean scores on the QLQ-C30 and EQ-5D-3L questionnaires increasing notably, especially among those who achieved a complete or partial response to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related quality of life with pembrolizumab monotherapy in patients with previously treated advanced microsatellite instability high/mismatch repair deficient endometrial cancer in the KEYNOTE-158 study. O'Malley, DM., Bariani, GM., Cassier, PA., et al.[2022]

A case of advanced endometrial clear cell carcinoma (CCC), which typically has a poor prognosis and is resistant to standard chemotherapy, showed a successful treatment response using a combination of pembrolizumab (an immunotherapy), localized radiotherapy, and a few cycles of chemotherapy.

The patient experienced an extremely durable response, maintaining benefits even 3 years after stopping immunotherapy, highlighting the potential effectiveness of this treatment strategy for difficult-to-treat CCC cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case report: Durable response after pembrolizumab in combination with radiation - induced abscopal effect in platinum - refractory metastatic endometrial clear cell carcinoma. Kao, CH., Liu, CT., Lin, H., et al.[2023]

Pembrolizumab, an immune checkpoint inhibitor, has been approved for treating relapsed MSI-H endometrial cancer after chemotherapy, showing promise in restoring anti-tumor immunity by blocking PD-1 interactions.

Despite encouraging response rates in MSI-H patients, over 50% do not respond to pembrolizumab, highlighting the need for better understanding of MSI status and identifying specific patient populations that may benefit from treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab as a single agent for patients with MSI-H advanced endometrial carcinoma. Turinetto, M., Lombardo, V., Pisano, C., et al.[2022]

References

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

Image-guided brachytherapy following external-beam radiation therapy for patients with inoperable endometrial cancer. [2023]

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

Does brachytherapy improve survival in addition to external beam radiation therapy in patients with high risk stage I and II endometrial carcinoma? [2010]

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

Implementation of image-guided brachytherapy as part of non-surgical treatment in inoperable endometrial cancer patients. [2021]

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

Addition of External Beam Radiation Therapy to Adjuvant Chemotherapy for Patients With Stage IIIC Uterine Endometrioid Carcinoma: Utilization and Outcomes. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Survival and recurrent disease after postoperative radiotherapy for early endometrial cancer: systematic review and meta-analysis. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Less gastrointestinal toxicity after adjuvant radiotherapy on a small pelvic field compared to a standard pelvic field in patients with endometrial carcinoma. [2018]

7. Singapore pubmed.ncbi.nlm.nih.gov

Adjuvant radiotherapy for endometrial cancer--a comparative review of radiotherapy technique with acute toxicity. [2020]

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

Definitive radiation therapy for endometrial cancer in medically inoperable elderly patients. [2010]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Use of electronic brachytherapy to deliver postsurgical adjuvant radiation therapy for endometrial cancer: a retrospective multicenter study. [2021]

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

New Approved Use for Keytruda. [2022]

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

Health-related quality of life with pembrolizumab monotherapy in patients with previously treated advanced microsatellite instability high/mismatch repair deficient endometrial cancer in the KEYNOTE-158 study. [2022]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Case report: Durable response after pembrolizumab in combination with radiation - induced abscopal effect in platinum - refractory metastatic endometrial clear cell carcinoma. [2023]

13. Netherlands pubmed.ncbi.nlm.nih.gov

Complete resection after pembrolizumab treatment followed by salvage surgery in stage IVB endometrial cancer: A case report. [2022]

14. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab as a single agent for patients with MSI-H advanced endometrial carcinoma. [2022]