Frontline Immunotherapy Combined With Radiation and Chemotherapy in High Risk Endometrial Cancer

NCT03932409 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: OU-SCC-FIERCE
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this single arm, open label study is to evaluate the feasibility of pembrolizumab combined with radiation administered to the upper part of the vagina (vaginal cuff brachytherapy) followed by three cycles of pembrolizumab and chemotherapy in patients with endometrial cancer.

Conditions

Endometrial Cancer

Keywords

pembrolizumab; radiation therapy

Outcome Measures

Primary Outcomes (1)

• Proportion of patients completing three cycles

  defined as completion of 3 cycles of pembrolizumab combined with dose dense paclitaxel and carboplatin chemotherapy

  4 months

Secondary Outcomes (4)

• progression free survival

  up to 2 years

• progression free survival

  6 months

• Overall survival

  up to 2 years

• Frequency of adverse events

  5 months

Study Arms (1)

Pembrolizumab + Radiation Therapy + Pembrolizumab/Chemotherapy

EXPERIMENTAL

Pembrolizumab given 7 days prior to radiation therapy (e.g., vaginal cuff brachytherapy) followed by three cycles pembrolizumab combined with Carboplatin/Paclitaxel chemotherapy

Drug: Pembrolizumab; Radiation: Vaginal cuff brachytherapy (VCB); Drug: Paclitaxel; Drug: Carboplatin

Interventions

Carboplatin DRUG

after VCB, Carboplatin IV on day 1 of a 21 day cycle for 3 cycles

Pembrolizumab + Radiation Therapy + Pembrolizumab/Chemotherapy

Pembrolizumab DRUG

prior to VCB: 200mg IV given one week (7 days) before radiation after VCB: 200mg IV on day 1 of a 21 day cycle prior to chemotherapy

Also known as: MK3475

Pembrolizumab + Radiation Therapy + Pembrolizumab/Chemotherapy

Vaginal cuff brachytherapy (VCB) RADIATION

Treatment should commence within 12 weeks of the surgery/hysterectomy

Pembrolizumab + Radiation Therapy + Pembrolizumab/Chemotherapy

Paclitaxel DRUG

after VCB, Paclitaxel IV on days 1,8 and 15 of a 21 day cycle for 3 cycles

Pembrolizumab + Radiation Therapy + Pembrolizumab/Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients must have undergone hysterectomy. Bilateral salpingooophorectomy is strongly encouraged but not mandatory.
• Pelvic and para-aortic lymphadenectomy are optional, but strongly encouraged.
• 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.
• Tissue from an archival sample or newly obtained core or excisional biopsy of a tumor lesion within 10 weeks confirming diagnosis.
• 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:
• 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.
• Patients with Stage II endometrial carcinoma (any histology) with cervical stromal invasion (occult or gross involvement), with or without high-intermediate risk factors.
• 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.
• Patients must have ECOG performance status 0 or 1.
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial and authorization permitting release of personal health information.
• Neuropathy (sensory and motor) ≤ Grade 1.
• Have adequate organ function as defined per Protocol.

You may not qualify if:

• Patients with recurrent disease.
• Greater than 12 weeks elapsed from surgery to enrollment
• Patients have prior pelvic or abdominal radiation therapy
• Known hypersensitivity to any component of study treatments that resulted in drug discontinuation
• 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
• 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.
• 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.
• Has received a live vaccine within 30 days prior to the first dose of study drug.
• 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.
• 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.
• 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.
• Has known active CNS metastases and/or carcinomatous meningitis.
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
• 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.
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.

Sponsors & Collaborators

• University of Oklahoma: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (2)

LSU Health New Orleans

New Orleans, Louisiana, 70112, United States

Location

Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

MeSH Terms

Conditions

Endometrial Neoplasms

Interventions

pembrolizumab; Paclitaxel; Carboplatin

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes

Study Officials

• Christina Washington, MD

  Stephenson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2019
• First Posted: April 30, 2019
• Study Start: February 19, 2020
• Primary Completion: September 25, 2025
• Study Completion (Estimated): June 25, 2027
• Last Updated: May 8, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)