NCT03602586

Testing Whether the Combination of Two Immunotherapy Drugs Have Activity in Recurrent or Persistent Clear Cell Ovarian Cancer

A Phase II Study of MK-3475 (Pembrolizumab) (NSC #776864) + Epacadostat (NSC #766086) in Recurrent Clear Cell Carcinoma of the Ovary

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 14 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial studies how well pembrolizumab and epacadostat work in treating patients with ovarian clear cell carcinoma that has come back (recurrent), remains despite treatment (persistent), or is growing, spreading, or getting worse (progressive). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Epacadostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab and epacadostat may work better compared to usual treatment (surgery, radiation, or cytotoxic chemotherapy) in treating patients with ovarian clear cell carcinoma.

Detailed description

PRIMARY OBJECTIVE: I. To assess the objective tumor response (proportion of objective response by Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1 criteria) of the combination of pembrolizumab (MK-3475 \[pembrolizumab\]) and epacadostat in patients with recurrent or persistent clear cell carcinoma of the ovary. SECONDARY OBJECTIVES: I. To determine the nature and degree of toxicity of MK-3475 (pembrolizumab) + epacadostat as assessed by Common Terminology Criteria for Adverse Events (CTCAE) in patients with recurrent or persistent clear cell carcinoma of the ovary. II. To estimate the progression-free survival (PFS) and overall survival (OS) in patients treated with combination of MK-3475 (pembrolizumab) and epacadostat. EXPLORATORY TRANSLATIONAL OBJECTIVES: I. Determine whether the ratio of plasma tryptophan to kynurenine (T:K) correlates with response to MK-3475 (pembrolizumab) + epacadostat, by evaluating plasma T:K pre-treatment, during treatment, and at disease progression. II. Determine whether the presence of PD-L1, IDO-1, tumor-infiltrating regulatory T cells (Tregs), CD8 tumor-infiltrating lymphocytes (TILs), and human leukocyte antigen (HLA) class I in the tumor microenvironment at baseline correlates with objective response to MK-3475 (pembrolizumab) + epacadostat. III. Determine whether soluble PD-L1 (sPD-L1) levels in plasma are correlated with response to MK-3475 (pembrolizumab) + epacadostat, by evaluating sPD-L1 concentrations pre-treatment, during treatment, and at disease progression. OUTLINE: Patients receive epacadostat orally (PO) twice daily (BID) and pembrolizumab intravenously (IV) over 30 minutes once every 3 weeks (Q3W). Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years, then every 6 months for 3 years, and annually thereafter.

Conditions

• Malignant Ovarian Clear Cell Tumor
• Recurrent Ovarian Carcinoma

Interventions

Type	Name	Description
DRUG	Epacadostat	Given PO
BIOLOGICAL	Pembrolizumab	Given IV

Timeline

• Start date: 2018-12-21
• Primary completion: 2021-02-01
• Completion: 2024-03-27
• First posted: 2018-07-27
• Last updated: 2024-07-26
• Results posted: 2022-12-23

Locations

363 sites across 2 countries: United States, Puerto Rico

Regulatory

• FDA-regulated drug study