Neoplasms

All Conditions

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Carcinoma

Recurrence

Endometrial Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Antineoplastic Agents

All Drugs and Chemicals

Lenvatinib

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Participants in this group will receive a combination treatment of Lenvatinib, Pembrolizumab, and Hypofx Pelvic EBRT over a period of approximately 10 to 12 weeks.

1. Lenvatinib - administered in a 3 plus 3 escalation/de-escalation design. Participants will receive 1 of 4 of the following dose levels:

   Dose level 1- 4 mg Dose level 2- 8 mg Dose level 3 (Starting dose) - 12 mg Dose level 4- 16 mg
2. Pembrolizumab- 200 mg IV will be administered on Day 1, 22 and 43
3. HypoFx 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.

200 mg Pembrolizumab administered intravenously (IV) once on Days 1, 22 and 43.

HypoFx 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.

Hypofractionated External Beam Radiation Therapy

Aaron H Wolfson, MD, FACR

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.

Phase 1 Clinical Trial of Lenvatinib, Pembrolizumab and Hypofractionated Pelvic Radiation Therapy for pMMR Recurrent/Unresectable Endometrial Carcinoma

Phase 1 Clinical Trial of Lenvatinib, Pembrolizumab and Hypofractionated Pelvic Radiation Therapy for Mismatch Repair Proficient (pMMR) Recurrent/Unresectable Endometrial Carcinoma

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.

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.

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).

All other reported adverse events regardless of physicians' assessment of relation to study drugs using NCI CTCAE version 5.0

Aaron Wolfson

Professor of Radiation Oncology

Spots Global Cancer Trial Database for unresectable endometrial carcinoma