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Epacadostat and Pembrolizumab in Treating Participants With Advanced Pancreatic Cancer | Clinical Trials | Clareo Health

WITHDRAWNPHASE2

Epacadostat and Pembrolizumab in Treating Participants With Advanced Pancreatic Cancer

Single-Arm, Phase II Proof of Concept Study of IDO-1 Inhibitor Epacadostat in Combination With Pembrolizumab in Advanced Pancreatic Cancer With Chromosomal Instability/Homologous Recombination Repair Deficiency (HRD)

NCT03432676•M.D. Anderson Cancer Center

View on ClinicalTrials.gov

Summary

This phase II trial studies how well epacadostat and pembrolizumab work in treating participants with pancreatic cancer that has spread to other places in the body. Epacadostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. 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. Giving epacadostat and pembrolizumab may work better in treating participants with pancreatic cancer.

Detailed Description

PRIMARY OBJECTIVES: I. To determine the efficacy of epacadostat in combination with pembrolizumab as determined by the best overall response rate in previously treated patients with advanced pancreatic adenocarcinoma with homologous recombination repair deficiency (HRD) aberrations. SECONDARY OBJECTIVES: I. To further determine the efficacy of epacadostat in combination with pembrolizumab in previously treated patients with advanced pancreatic adenocarcinoma with HRD aberrations. II. To assess the safety and tolerability of epacadostat in combination with pembrolizumab in previously treated patients with advanced pancreatic adenocarcinoma with HRD aberrations. EXPLORATORY OBJECTIVES: I. To identify predictive, mechanistic, and/or surrogate biomarkers of clinical efficacy of epacadostat in combination with pembrolizumab in previously treated patients with advanced pancreatic adenocarcinoma with HRD aberrations utilizing exploratory studies investigating the patients tumor and immune system response including: flow cytometry of fresh peripheral blood mononuclear cell (PBMC), PDL-1. OUTLINE: Participants receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and epacadostat orally (PO) twice daily (BID) on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unaccepted toxicity. After completion of study treatment, participants are followed up at 30 days, every 8 weeks for 3 years, and then every 12 weeks thereafter.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Be willing and able to provide written informed consent/assent for the trial
•Have received at least one prior therapy for metastatic disease
•Patients with HRD identified by one of the following criteria: a) Tested positive for BRCA 1 or 2 germline deleterious mutation, b) Previously identified genetic aberrations that are associated with HRD (e.g., somatic BRCA mutation, PALB2, Fanconi anemia gene or RAD51 mutations), c) Patients with somatic ATM loss as identifiable with immunohistochemistry or with ATM mutation, d) Pancreatic ductal adenocarcinoma (PDAC) patients with family history of 2 or more first-degree relatives with BRCA-associated cancers (stomach, breast, ovary) or 1 or more first-degree relative with PDAC
•Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or at least one site of disease must be uni-dimensionally measurable as per RECIST 1.1. All radiology studies must be performed within 28 days prior to registration
•Patients must have an archival sample of tumor or metastatic site core biopsy to be eligible
•Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
•Within 10 days of treatment initiation: Absolute neutrophil count (ANC) \>= 1.5 x 109/L
•Within 10 days of treatment initiation: platelet count \>= 100 x 109/L
•Within 10 days of treatment initiation: hemoglobin \>= 9 g/dl without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment)
•Within 10 days of treatment initiation: If serum creatinine concentration \>= 1.5 x upper limit of normal (ULN), then estimated creatinine clearance must be \>= 60 mL/min for subject with creatinine levels \> 1.5 x institutional ULN
+6 more criteria

Exclusion Criteria

•Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
•For screening electrocardiographs (ECGs), exclude patients with a Fridericia's corrected QT interval (QTcF) \> 480 ms, or JTc \> 340 ms for those with an intraventricular conduction delay. If the screening ECG has a QTcF \> 480 ms, eligibility can be confirmed if the average of 3 ECGs done 5 minutes apart have an average QTcF \< 480 ms
•Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
•Has a known history of active TB (Bacillus tuberculosis)
•Hypersensitivity to pembrolizumab or epacadostat or any of their excipients
•Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
•Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to a previously administered agent. Note: Subjects with =\< grade 2 neuropathy are an exception to this criterion and may qualify for the study. Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
•Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
•Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability
•Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
+13 more criteria

Key Dates

Start Date

July 31, 2019

Primary Completion Date

April 30, 2020

Completion Date

April 30, 2021

Last Updated

May 30, 2019

Conditions

ATM Gene MutationDeleterious BRCA1 Gene MutationDeleterious BRCA2 Gene MutationHomologous Recombination DeficiencyPancreatic Ductal AdenocarcinomaStage II Pancreatic Cancer AJCC v8Stage IIA Pancreatic Cancer AJCC v8Stage IIB Pancreatic Cancer AJCC v8Stage III Pancreatic Cancer AJCC v8Stage IV Pancreatic Cancer AJCC v8

Interventions

Epacadostat

DRUG

Pembrolizumab

BIOLOGICAL

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ATM Gene MutationBRCA1 Gene Mutation+8 more

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COMPLETEDPHASE2

Rucaparib in Treating Patients With Genomic LOH High and/or Deleterious BRCA1/2 Mutation Stage IV or Recurrent Non-small Cell Lung Cancer (A Lung-MAP Treatment Trial)

NCT03845296

Deleterious BRCA1 Gene MutationDeleterious BRCA2 Gene Mutation+9 more

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: May 30, 2019Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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