Epacadostat and Pembrolizumab Before Surgery in Treating Participants With Stage II-III Esophageal or Gastroesophageal Cancer

Esophageal Squamous Cell Carcinoma Clinical Trial

Official title: A Phase 2 Trial of Neoadjuvant Pembrolizumab in Combination With Epacadostat (INCB024360) in Patients With Non-Metastatic Esophageal/Gastroesophageal Squamous Cell and Adenocarcinomas Treated With Neoadjuvant Chemoradiation: A Window-Of-Opportunity Study

Status Withdrawn

Clinical Trial Summary

This phase II trial studies the side effects of epacadostat and pembrolizumab and to see how well they work before surgery in treating participants with stage II-III esophageal or gastroesophageal cancer. Epacadostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of the tumor cells to grow and spread. Giving epacadostat and pembrolizumab before surgery may work better in treating participants with stage II-III esophageal or gastroesophageal cancer.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To establish that the combination of epacadostat and pembrolizumab will lead to an increase in tumor infiltrating cytotoxic T-cells and circulating cytotoxic T cells and a reduction in immunosuppressive Tregs and myeloid-derived suppressor cells (MDSCs) in esophageal/gastroesophageal junction (GEJ) tumors that can arise after treatment with neoadjuvant chemoradiation.

II. To assess safety and tolerability of pembrolizumab and epacadostat (immunotherapy) in this patient population.

SECONDARY OBJECTIVES:

I. To evaluate pathologic complete response rate (path CR) and correlate with tumor T-cell response.

II. To evaluate complete clinical response rate (clinical CR) and subsequent avoidance of esophagectomy and correlate with tumor T-cell response.

III. To evaluate toxicities with the combination of pembrolizumab and epacadostat in this treatment setting.

IV. To evaluate disease-free survival (DFS) and overall survival (OS) in this treatment population.

EXPLORATORY OBJECTIVES:

I. To measure changes in whole genome serum micro ribonucleic acid (miRNA) signatures before and after protocol therapy and correlate with tumor/immune/stromal cell miRNA expression profiling determined by deep sequencing.

II. To assess the role of circulating miR-23a as serum biomarker given its role as an oncomir in esophagastric cancer and reporting in the literature of suppressing tumor cytotoxic T cells in preclinical models.

III. To correlate diversity in the gut microbiome with path CR and clinical CR after treatment with pembrolizumab and epacadostat.

IV. To measure serial plasma kynurenine/tryptophan ratio levels as a pharmacodynamic marker of increased IDO1 activity and response.

V. Association of PD-L1 expression, microsatellite stability and/or IDO1 expression and pathological complete response (pCR) rate.

OUTLINE:

Starting 14 days after completion of standard of care chemoradiotherapy, participants receive epacadostat orally (PO) twice daily (BID) during weeks 3-8 and pembrolizumab intravenously (IV) over 30 minutes on day 1 of weeks 3 and 6 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed up at one month and then every 3 months in year 1, every 4 months in year 2, and every 6 months in year 3. ;

Related Conditions & MeSH terms

• Adenocarcinoma
• Esophageal Adenocarcinoma
• Esophageal Squamous Cell Carcinoma
• Gastroesophageal Junction Adenocarcinoma

• NCT number: NCT03592407
• Study type: Interventional
• Source: City of Hope Medical Center
• Status: Withdrawn
• Phase: Phase 2
• Start date: July 1, 2018
• Completion date: April 2020