Clinical Trials /

Epacadostat, Pembrolizumab, and CRS-207, With or Without CY/GVAX Pancreas in Patients With Metastatic Pancreas Cancer

NCT03006302

Description:

This study will enroll patients who have metastatic pancreatic cancer and have progressed on prior chemotherapy. Half of participants will receive epacadostat/pembrolizumab/cyclophosphamide(CY)/GVAX pancreas vaccine followed by epacadostat/pembrolizumab/CRS-207 (Arm A), while the other half will receive epacadostat/pembrolizumab/CRS-207 (Arm B). 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.

Related Conditions:
  • Pancreatic Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: J16173
  • SECONDARY ID: IRB00118520
  • NCT ID: NCT03006302

Conditions

  • Metastatic Pancreatic Adenocarcinoma

Interventions

DrugSynonymsArms
EpacadostatINCB024360Epacadostat/Pembrolizumab/CY/GVAX/CRS-207
PembrolizumabMK-3475, anti-PD-1 mAbEpacadostat/Pembrolizumab/CY/GVAX/CRS-207
CRS-207Epacadostat/Pembrolizumab/CY/GVAX/CRS-207
CYcyclophosphamide, cytoxanEpacadostat/Pembrolizumab/CY/GVAX/CRS-207
GVAXGVAX Pancreas Vaccine, Panc 10.05 pcDNA-1/GM-Neo, Panc 6.03 pcDNA-1/GM-NeoEpacadostat/Pembrolizumab/CY/GVAX/CRS-207

Purpose

This study will enroll patients who have metastatic pancreatic cancer and have progressed on prior chemotherapy. Half of participants will receive epacadostat/pembrolizumab/cyclophosphamide(CY)/GVAX pancreas vaccine followed by epacadostat/pembrolizumab/CRS-207 (Arm A), while the other half will receive epacadostat/pembrolizumab/CRS-207 (Arm B). 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.

Trial Arms

NameTypeDescriptionInterventions
Epacadostat/Pembrolizumab/CY/GVAX/CRS-207Experimental
  • Epacadostat
  • Pembrolizumab
  • CRS-207
  • CY
  • GVAX
Epacadostat/Pembrolizumab/CRS-207Experimental
  • Epacadostat
  • Pembrolizumab
  • CRS-207

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Recommended Dose of Epacadostat
Time Frame:1 year
Safety Issue:
Description:Evaluate 3 dose levels of epacadostat, in order to determine recommended dose for use in combination with pembrolizumab, CY, GVAX, and CRS-207

Secondary Outcome Measures

Measure:Number of patients experiencing treatment related toxicities
Time Frame:4 years
Safety Issue:
Description:
Measure:Overall Survival (OS)
Time Frame:4 years
Safety Issue:
Description:Average time from randomization to death due to any cause
Measure:Progression Free Survival (PFS)
Time Frame:4 years
Safety Issue:
Description:Average time from randomization to disease progression (by RECIST 1.1) or death, whichever comes first
Measure:immune-related Progression Free Survival (irPFS)
Time Frame:4 years
Safety Issue:
Description:Average time from randomization to disease progression (by irRC) or death, whichever comes first.
Measure:Objective Response Rate (ORR)
Time Frame:4 years
Safety Issue:
Description:Proportion of subjects who achieve a Complete Response (CR) or Partial Response (PR) by RECIST 1.1
Measure:immune-related Objective Response Rate (irORR)
Time Frame:4 years
Safety Issue:
Description:Proportion of subjects who achieve a Complete Response (CR) or Partial Response (PR) by irRC
Measure:Best Overall Response (BOR)
Time Frame:4 years
Safety Issue:
Description:Summary of the best response (by RECIST 1.1) achieved by each patient
Measure:immune-related Best Overall Response (irBOR)
Time Frame:4 years
Safety Issue:
Description:Summary of the best response (by irRC) achieved by each patient
Measure:Time to Objective Response (TTOR)
Time Frame:4 years
Safety Issue:
Description:Average time from randomization to partial or complete response by RECIST 1.1
Measure:immune-related Time to Objective Response (irTTOR)
Time Frame:4 years
Safety Issue:
Description:Average time from randomization to partial or complete response by irRC
Measure:Duration of Response (DOR)
Time Frame:4 years
Safety Issue:
Description:Average time from partial or complete response to disease progression, by RECIST 1.1
Measure:immune-related Duration of Response (irDOR)
Time Frame:4 years
Safety Issue:
Description:Average time from partial or complete response to disease progression, by irRC
Measure:Duration of Clinical Benefit (DCB)
Time Frame:4 years
Safety Issue:
Description:Average time from randomization to date of disease progression in subjects achieving a partial or complete response by RECIST 1.1
Measure:immune-related Duration of Clinical Benefit (irDCB)
Time Frame:4 years
Safety Issue:
Description:Average time from randomization to date of disease progression in subjects achieving a partial or complete response by RECIST 1.1
Measure:Disease Control Rate (DCR)
Time Frame:4 years
Safety Issue:
Description:Percentage of subjects achieving stable disease or better by RECIST 1.1
Measure:immune-related Disease Control Rate (irDCR)
Time Frame:4 years
Safety Issue:
Description:Percentage of subjects achieving stable disease or better by irRC
Measure:Tumor Marker (CA19-9) Kinetics
Time Frame:4 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Trial Keywords

  • pancreatic cancer
  • vaccine
  • immunotherapy
  • MK-3475
  • PD-1
  • IDO

Last Updated

February 1, 2019