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Clinical Trial 19641

Cancer Type: Gynecological Tumor
Interventions:BMS-936558 (Nivolumab); Cabozantinib (XL 184); Nivolumab; Not Applicable

Study Type: Treatment
Phase of Study: Phase II
Investigators:

  • Jing-Yi Chern

Call 813-745-6100
or 1-800-679-0775
Overview

Study Title

A Randomized Phase 2 Study of Cabozantinib in Combination with Nivolumab in Advanced, Recurrent Metastatic Endometrial Cancer

Summary

The purpose of this study is to compare any good and bad effects of using the drug cabozantinib along with the the drug nivolumab to using the drug nivolumab alone.

Objective

Primary Objectives: -To evaluate the clinical anti-tumor activity of XL184 (cabozantinib) and nivolumab based on progression free survival (PFS) in patients with advanced, recurrent ormetastatic endometrial cancer previously treated with at least one line of platinum-based chemotherapy compared to patients receiving nivolumab alone. Secondary Objectives: - To evaluate the efficacy of XL184 and nivolumab in terms of overall response rate (ORR) compared to nivolumab alone. - To evaluate overall survival (OS) of patients receiving XL184 and nivolumab compared to patients receiving nivolumab alone. - To evaluate the safety of combination treatment using XL184 and nivolumab in patients with advanced, recurrentmetastatic endometrial cancer. - To evaluate correlation between PD-L1 expression, CD3, CD4 and CD8 infiltrates and outcome (PFS, ORR, OS). - To compare PD-L1 expression, CD3, CD4 and CD8 infiltrates in the primary tumor (archival tissue) and in the tissue from baseline biopsy. - To assess activity (PFS, ORR and OS) of nivolumab alone or in combination with XL184 according to MSI/MMR status. Exploratory Objectives: - To assess activity (PFS, ORR and OS) of XL184 and nivolumab in patients progressed after previous exposure to anti PD-1, PD-L1 or PD-L2 agents or crossed-over from single agent nivolumab, and in patients with diagnosis of carcinosarcoma. - To compare MS and MMR status, in the primary tumor (archival tissue) and in the tissue from baseline biopsy. - To assess the genomic and immune-markers landscape at baseline on tumor tissue and changes in immune landscape in peripheral blood during treatment and correlate with outcome

Inclusion Criteria

  • Participants must have histologically or cytologically confirmed epithelial endometrial carcinoma; all histologies are accepted. Must have advance, recurrent or metastatic endometrial cancer.
  • Must have radiological evidence of disease progression following the most recent treatment.
  • Must have measurable disease according Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Adequate organ function
  • Must have disease amenable to biopsy and must agree to have one baseline biopsy
  • Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test at screening and must agree to use adequate contraception prior to study entry and for the duration of study participation. WOCBP should use an adequate method to avoid pregnancy for 7 months after the last dose of investigational drug; women must not be breastfeeding.
  • Ability to understand and the willingness to sign a written informed consent document
  • Additional criteria may apply

  • Exclusion Criteria

  • Have had chemotherapy (including investigational cytotoxic chemotherapy), biologic agents (e.g., targeted therapy or antibodies) or radiotherapy within 4 weeks prior to the first dose of study treatment
  • Have not recovered from adverse events attributed to prior anti-cancer therapy
  • Are receiving any other investigational agents
  • Any other active malignancy other than the endometrial cancer, that is progressing or requiring active treatment with the exception of basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of any site
  • A known brain metastases
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to cabozantinib or nivolumab
  • Clinically-significant gastrointestinal bleeding within 6 months before the first dose of study treatment;
  • Hemoptysis of >= 0.5 teaspoon (2.5 mL) of red blood within 3 months before the first dose of study treatment;
  • Radiographic evidence of cavitating pulmonary lesion(s)
  • Has uncontrolled, significant intercurrent or recent illness including
  • Active infection requiring systemic treatment within 28 days before the first dose of study treatment
  • Serious non-healing wound/ulcer/bone fracture within 28 days before the first dose of study treatment
  • History of organ transplant
  • Concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days before the first dose of study treatment
  • Major surgery within 3 months of the first dose of cabozantinib if there were no wound healing complications or within 6 months of the first dose of cabozantinib if there were wound complications
  • Minor surgery within 1 month of the first dose of cabozantinib if there were no wound healing complications or within 3 months of the first dose of cabozantinib if there were wound complications
  • In addition, complete wound healing from prior surgery must be confirmed at least 28 days before the first dose of cabozantinib irrespective of the time from surgery
  • Known active human immunodeficiency virus (HIV), acquired immunodeficiency syndrome (AIDS) related illness, or hepatitis B or C infection
  • Administration of a live vaccine within 4 weeks prior to start of protocol therapy
  • Psychiatric illness/social situations that would limit compliance with study requirements
  • Not able to swallow pills
  • Additional criteria may apply