Combining immunotherapy with radiation and chemotherapy for high-risk endometrial cancer

A Phase Ib Trial of Vaginal Cuff Brachytherapy + Pembrolizumab (MK3475) Followed by 3 Cycles of Dose Dense Paclitaxel/q 21 Day Carboplatin + Pembrolizumab (MK3475) in High Intermediate Risk Endometrial Cancer

This study is testing whether combining an immunotherapy drug with radiation and chemotherapy can help people with high-risk endometrial cancer after surgery.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 45 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: University of Oklahoma (Academic / other)
• Drugs / interventions: pembrolizumab, radiation, prednisone, chemotherapy
• Locations: 2 sites (New Orleans, Louisiana and 1 other locations)
• Trial ID: NCT03932409 on ClinicalTrials.gov

What this trial studies

This study evaluates the feasibility of using pembrolizumab, an immunotherapy drug, in combination with vaginal cuff brachytherapy and subsequent chemotherapy in patients with high-risk endometrial cancer. Eligible patients must have undergone surgery, including hysterectomy, and will receive pembrolizumab prior to radiation therapy, followed by three cycles of pembrolizumab and chemotherapy. The study aims to assess the effectiveness and safety of this treatment approach over a participation period of up to two years.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older who have undergone hysterectomy and have high-intermediate risk factors for endometrial cancer.

Not a fit: Patients with metastatic endometrial cancer or those who have not undergone the necessary surgical procedures may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve outcomes for patients with high-risk endometrial cancer by reducing the risk of cancer recurrence.

How similar studies have performed: Other studies have shown promising results with similar combinations of immunotherapy and chemotherapy, suggesting potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. All patients must have undergone hysterectomy. Bilateral salpingooophorectomy is strongly encouraged but not mandatory.
2. Pelvic and para-aortic lymphadenectomy are optional, but strongly encouraged.
3. If either a bilateral salpingo-oophorectomy (BSO) or nodal sampling was not performed, post-operative pre-treatment CT/MRI is required and must not demonstrate evidence suggestive of metastatic disease (adnexa, nodes, intraperitoneal disease). Post-operative, pre-treatment CT/MRI must be performed if a BSO and/or lymphnode sampling was not performed.
4. Tissue from an archival sample or newly obtained core or excisional biopsy of a tumor lesion within 10 weeks confirming diagnosis.
5. All patients will be staged according to the FIGO 2009 staging system and with endometrial carcinoma (endometrioid types) confined to the corpus uteri or with endocervical glandular involvement fitting one of the following high-intermediate risk factor categories:

   * age ≥18 years with 3 risk factors
   * Risk factors:

     1. Grade 2 or 3 tumor, (+) lymphovascular space invasion, outer ½ myometrial invasion. Patients with these risk criteria may be enrolled with either positive or negative cytology.
     2. Patients with Stage II endometrial carcinoma (any histology) with cervical stromal invasion (occult or gross involvement), with or without high-intermediate risk factors.
     3. Patients with serous or clear cell histology (with or without other high-intermediate risk factors) are eligible provided the disease is Stage I or II (with or without cervical stromal invasion or endocervical glandular involvement). Eligibility for clear cell and serous histology is not based on presence of lymphovascular space invasion or depth of invasion.
6. Patients must have ECOG performance status 0 or 1.
7. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial and authorization permitting release of personal health information.
8. Neuropathy (sensory and motor) ≤ Grade 1.
9. Have adequate organ function as defined per Protocol.

Exclusion Criteria:

1. Patients with recurrent disease.
2. Greater than 12 weeks elapsed from surgery to enrollment
3. Patients have prior pelvic or abdominal radiation therapy
4. Known hypersensitivity to any component of study treatments that resulted in drug discontinuation
5. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor
6. Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks \[could consider shorter interval for kinase inhibitors or other short half-life drugs\] prior to allocation.
7. Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
8. Has received a live vaccine within 30 days prior to the first dose of study drug.
9. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
10. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
11. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
12. Has known active CNS metastases and/or carcinomatous meningitis.
13. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
14. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
15. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
16. Has an active infection requiring systemic therapy. This excludes grade 2 urinary tract infections or grade 1-2 skin infections.
17. Has a known history of Human Immunodeficiency Virus (HIV).
18. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection.
19. Has a known history of active TB (Bacillus Tuberculosis).
20. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
21. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
22. Is pregnant or breastfeeding

Where this trial is running

New Orleans, Louisiana and 1 other locations

• LSU Health New Orleans — New Orleans, Louisiana, United States (Recruiting)
• Stephenson Cancer Center — Oklahoma City, Oklahoma, United States (Recruiting)

Study contacts

• Principal investigator: Christina Washington, MD — Stephenson Cancer Center
• Study coordinator: Lead Gyn Nurse

Conditions Endometrial Cancer; pembrolizumab; radiation therapy