The purpose of this research study is to see if it is feasible to combine a fixed dose of pembrolizumab and a daily dose of oral lenvatinib, along with daily treatments of an abbreviated course of pelvic external beam radiation therapy, to support cancer cells in multiplying and spreading to other body sites.
Biopsy-proven recurrent pMMR EC following surgery alone or de novo unresectable pMMR EC for whom External beam radiation therapy (EBRT) has been determined as an appropriate therapeutic approach. Eligible tumor histologies include the following: endometrioid adenocarcinoma, adenocarcinoma with squamous differentiation, mucinous, mixed carcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, and serous adenocarcinoma histologies as determined by tissue from an archival sample or newly obtained core or excisional biopsy of a tumor lesion. For patients with recurrent disease greater than six months (>6 months), a fresh biopsy must be obtained.
Measurable disease of at least 1.0 cm in size defined by RECIST 1.1 on imaging studies with at least one (1) site located in the pelvis and/or vagina without any foci of extra-pelvic disease (including the para-aortic region or inguinal-femoral lymph nodes).13
Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (Karnofsky score ≥50).
Patients must have pMMR tumor subtype(s).
Patients who are currently in or have participated in a study of an investigational agent or used an investigational device within 4 weeks of the first dose of study treatment.
Patients with Mismatch repair deficient (dMMR) and endometrial carcinomas.
Patients with dMMR and uterine carcinosarcomas.
Patients with known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
Single group
Lenvatinib
DrugLenvatinib capsules taken daily by mouth
Pembrolizumab
Drug200 mg Pembrolizumab administered intravenously (IV) once on Days 1, 22 and 43.
Hypofractionated External Beam Radiation Therapy
RadiationHypoFx whole pelvic EBRT begins on Day 22 and continues for a total of 16 fractions of radiation given at a dose of 2.5 Gy per fraction for a total dose of 40.0 Gy delivered to the pelvis. A pelvic boost HypoFx EBRT consisting of 7 fractions of radiation given at a dose of 2.5 Gy per fraction that will be delivered to site(s) of gross disease of at least 1.0 cm in size. An additional boost total dose of 17.5 Gy administered will be administered over a period of 1.5 to 2.0 weeks.
Recommended Phase 2 Dose (RP2D) of Lenvatinib
The RP2D will be the highest dose of Lenvatinib that in combination with Pembrolizumab and Hypofractionated (HypoFx) pelvic External Beam Radiotherapy (EBRT) yields less than 2 Dose Limiting Toxicities (DLTs) in 6 patients.
Number of Events of Treatment-Related Toxicity
The number of events of any treatment related (an attribution of definite, possible or probable relation to study treatment) DLTs and any toxicity or Adverse Events (AE) will be assessed by treating physician using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.
Overall Response Rate (ORR)
ORR is defined as the proportion of study patients achieving a Complete Response (CR) or Partial Response (PR) using Response Evaluation Criteria in Solid Tumors (RECIST v1.1).
Number of Reported Adverse Events
All other reported adverse events regardless of physicians' assessment of relation to study drugs using NCI CTCAE version 5.0
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Aaron Wolfson
Lead sponsor
University of Miami
Sponsor institution
