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

NCT03592407 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: 17302NCI-2018-00682
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Esophageal Squamous Cell Carcinoma; Esophageal Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma

Outcome Measures

Primary Outcomes (2)

• Temporal anti-tumor immune response defined as tumor infiltrating cytotoxic T-cells, circulating T-cells, T regulatory cells (Tregs), and myeloid-derived suppressor cells (MDSCs) in tumor and blood samples

  Patient demographics and baseline disease/prior treatment characteristics will be summarized using descriptive statistics. Descriptive statistics will be used to summarize the gene expression profile in tissue/blood. Changes in these measures during and after treatment (when measured) will also be summarized by descriptive statistics and tables/plots. Various statistical analyses will be used to explore the association between these gene expression measures (at different time points and the changes over time) with clinical outcomes. For the exploratory correlation of these endpoints with response, analyses comparing groups of participants defined by response may be conducted by two-sample t-test or Wilcoxon rank sum test.

  Baseline to 3 years

• Incidence of adverse events per Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.0

  All participants evaluable for toxicity will be included in the toxicity analysis. Observed toxicities will be summarized in terms of type (organ affected or laboratory determination), severity, time of onset, duration, probable association with the study treatment and reversibility or outcome.

  Up to 8 weeks

Secondary Outcomes (5)

• Pathological complete response (CR)

  Up to 3 years

• Clinical complete response

  Up to 3 years

• Incidence of adverse events per CTCAE v 4.0

  Up to 3 years

• Disease free survival (DFS)

  From start of neoadjuvant therapy up to 3 years

• Overall survival (OS)

  From start of neoadjuvant therapy up to 3 years

Study Arms (1)

Treatment (epacadostat, pembrolizumab)

EXPERIMENTAL

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

Drug: Epacadostat; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab; Other: Pharmacodynamic Study

Interventions

Epacadostat DRUG

Given PO

Also known as: INCB 024360, INCB024360

Treatment (epacadostat, pembrolizumab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (epacadostat, pembrolizumab)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (epacadostat, pembrolizumab)

Pharmacodynamic Study OTHER

Correlative studies

Also known as: PHARMACODYNAMIC

Treatment (epacadostat, pembrolizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented informed consent of the participant and/or legally authorized representative
• Agreement to allow the use of archival tissue from diagnostic tumor biopsies
• If unavailable, exceptions may be granted only with study principal investigator (PI) approval
• Eastern Cooperative Oncology Group (ECOG) =\< 2
• Non-metastatic cancer of the esophagus OR esophagus and gastroesophageal junction (GEJ; tumor extending =\< 2 cm into the stomach)
• Confirmed stage II-III diagnosis of one of the following:
• Squamous cell; OR
• Adenocarcinoma; OR
• Mixed adenosquamous carcinoma
• Deemed appropriate for neoadjuvant chemoradiation by the multidisciplinary team (surgeon, medical oncologist, and radiation oncologist)
• Chemotherapy defined as weekly carboplatin/paclitaxel; AND
• Radiation defined as external beam radiotherapy defined as: 50.4 gray (Gy) as per institutional and national treatment guidelines
• Deemed appropriate for esophagectomy or repeat endoscopic biopsies if non-operative management is pursued
• Absolute neutrophil count (ANC) \>= 1500/mm\^3 within 14 days prior to day 1 of study participation/1st endoscopic biopsy
• Platelets \>= 100,000/mm\^3 within 14 days prior to day 1 of study participation/1st endoscopic biopsy

You may not qualify if:

• Immune checkpoint inhibitor(s) (e.g. anti-PD-1, anti-CTLA4)
• Indoleamine-2,3-dioxygenase (IDO) inhibitors
• Radiotherapy within 21 days prior to day 1 of study participation
• Investigational agent within 21 days prior to Day 1 of study participation
• Live-virus vaccination within 30 days prior to Day 1 of study participation
• Systemic cytotoxic chemotherapy, antineoplastic biologic therapy, or major surgery within 21 days of study participation
• Chronic systemic steroid therapy or on any other form of immunosuppressive medication
• Monoamine oxidase inhibitors (MAOI) or any drug associated with MAOI activity
• Any UGT1A9 inhibitors (including acitretin, amitriptyline, androsterone, cyclosporine, dasatinib, diclofenac, diflunisal, efavirenz, erlotinib, estradiol (17-beta), flutamide, gefitinib, gemfibrozil, glycyrrhetinic acid glycyrrhizin, imatinib, imipramine, ketoconazole, linoleic acid supplements, mefenamic acid, and mycophenolic acid, niflumic acid, nilotinib, phenobarbital, phenylbutazone, phenytoin, probenecid)
• Coumarin-based anticoagulants
• Unstable or untreated brain/leptomeningeal metastasis
• Clinically active diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction, or abdominal carcinomatosis (known risks factors for bowel perforation)
• Severe hypersensitivity reaction to treatment with another antibody and/or hypersensitivity to epacadostat excipients
• Active autoimmune disease that has required systemic treatment in the past 2 years
• Known history of human immunodeficiency virus (HIV), hepatitis B or hepatitis C (with confirmation of negative hepatitis B surface antigen \[HBsAg\], hepatitis B virus \[HBV\] polymerase chain reaction \[PCR\], and hepatitis C virus \[HCV\] PCR)

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

City of Hope South Pasadena

South Pasadena, California, 91030, United States

Location

City of Hope West Covina

West Covina, California, 91790, United States

Location

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma; Adenocarcinoma Of Esophagus

Interventions

epacadostat; pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Study Officials

• Joseph Chao, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 30, 2018
• First Posted: July 19, 2018
• Study Start: July 1, 2018
• Primary Completion: April 1, 2020
• Study Completion: April 1, 2020
• Last Updated: March 8, 2022

Record last verified: 2022-02

Locations

US (3)