Clinical trial NCT03006302: Epacadostat, Pembrolizumab, and CRS-207, With or Without CY/GVAX Pancreas in Patients With Metastatic Pancreas Cancer
Official title: Phase 2 Study of Epacadostat, Pembrolizumab, and CRS-207, With or Without Cyclophosphamide and GVAX Pancreas Vaccine in Patients With Metastatic Pancreas Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Pancreatic Adenocarcinoma
Keywords: Pancreatic cancer
Vaccine
Immunotherapy
Pembrolizumab
PD-1
IDO
CRS-207
Epacadostat
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
name: National Cancer Institute (NCI)
name: Incyte Corporation
First posted: 2016-12-30
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will enroll patients who have metastatic pancreatic cancer and have progressed on prior chemotherapy.

Part 1 (dose escalation) participants will receive epacadostat/pembrolizumab/cyclophosphamide(CY)/GVAX pancreas vaccine followed by epacadostat/pembrolizumab/CRS-207, Part 1X (dose escalation) participants will receive epacadostat/pembrolizumab/CRS-207. Part 2X (dose expansion) participants will receive epacadostat/pembrolizumab/CRS-207.

The primary objectives of this study are to determine the recommended dose of epacadostat in this combination and assess survival of subjects in both treatment groups.


Eligibility criteria: Inclusion Criteria (abbreviated):

* Documented adenocarcinoma of the pancreas
* Have disease progression after prior chemotherapy for metastatic pancreas cancer (or adjuvant or neoadjuvant if progression occurred within 6 months of completing this regimen)
* Presence of at least one measurable lesion
* Patient acceptance to have a tumor biopsy of an accessible lesion at 2 time points (baseline and on study)
* ECOG performance status of 0 or 1
* Life expectancy of greater than 3 months
* Adequate organ and marrow function defined by study-specified laboratory tests

Exclusion Criteria (abbreviated):

* Brain metastases
* Clinical or radiographic ascites (some trace amount may be allowed)
* Rapidly progressing disease
* Live vaccine within 30 days of study treatment (flu vaccine allowed)
* Surgery within 28 days of study treatment (some exceptions for minor procedures)
* Use of an investigational agent or device within 28 days of study treatment.
* Chemotherapy, radiation, or biological cancer therapy within 14 days of study treatment.
* Prior treatment with anti-CTLA-4, anti-PD-1, anti-PD-L1, or anti PD-L2, or with IDO inhibitor.
* Use of growth factors within 14 days of study treatment
* Use of any systemic steroids within 14 days of study treatment or other immunosuppressive agents within 7 days of study treatment.
* Use of more than 2 g/day of acetaminophen
* Use of any UGT1A9 inhibitor
* Use of warfarin
* Use of MAOIs or drugs with significant MAOI activity within the 21 days of screening
* History of Seratonin Syndome
* Known allergy to both penicillin and sulfa
* Known or suspected hypersensitivity to any monoclonal antibody or any study drug component
* Have artificial joints or implants that cannot be easily removed or a history of infection associated with an implant
* Significant or malignant pleural effusion
* New pulmonary embolism, extremity deep venous thromboembolism, or portal vein thrombosis within 2 months of study enrollment
* History of autoimmune disease (exceptions for Graves or Hashimoto's disease, vitiligo, and type I diabetes mellitus)
* Gastrointestinal condition that may affect drug absorption
* Significant heart disease or heart disease requiring antibiotic for prevention of endocarditis
* History of abnormal electrocardiogram (ECG) that is deemed meaningful by the investigator
* History of (non-infectious) pneumonitis that required steroids, evidence of interstitial lung disease or active, non-infectious pneumonitis
* Pulse oximetry of \< 92% on room air or the need for supplemental home oxygen
* Infection with HIV, hepatitis B or hepatitis C
* Other conditions, including alcohol or drug dependence, intercurrent illness, or lack of sufficient peripheral venous access that would affect the patient's ability to comply with study visits and procedures
* Pregnant or breastfeeding women
* Unwillingness or inability to follow the study schedule for any reason

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of Epacadostat
timeFrame: 9 weeks
measure: 6 Month Survival
timeFrame: 6 months
Secondary outcomes:
measure: Number of Participants Experiencing Drug-Related Adverse Events (AEs) Requiring Treatment Discontinuation
timeFrame: 15 months
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
Study officials:
affiliation: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Dung Le, M.D.
role: PRINCIPAL_INVESTIGATOR
References: