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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03006302
Recruitment Status : Recruiting
First Posted : December 30, 2016
Last Update Posted : August 20, 2021
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Tracking Information
First Submitted Date  ICMJE December 28, 2016
First Posted Date  ICMJE December 30, 2016
Last Update Posted Date August 20, 2021
Actual Study Start Date  ICMJE January 23, 2018
Estimated Primary Completion Date February 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 13, 2020)
  • Recommended Dose of Epacadostat [ Time Frame: 1 year ]
    Evaluate 4 dose levels of epacadostat, in order to determine recommended dose for use in combination with pembrolizumab, CY, GVAX, and CRS-207
  • 6 Month Survival [ Time Frame: 4 years ]
    Proportion of subjects who are alive 6 months or longer after the date of randomization
Original Primary Outcome Measures  ICMJE
 (submitted: December 28, 2016)
  • Recommended Dose of Epacadostat [ Time Frame: 1 year ]
    Evaluate 3 dose levels of epacadostat, in order to determine recommended dose for use in combination with pembrolizumab, CY, GVAX, and CRS-207
  • 6 Month Survival [ Time Frame: 4 years ]
    Proportion of subjects who are alive 6 months or longer after the date of randomization
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 28, 2016)
  • Number of patients experiencing treatment related toxicities [ Time Frame: 4 years ]
  • Overall Survival (OS) [ Time Frame: 4 years ]
    Average time from randomization to death due to any cause
  • Progression Free Survival (PFS) [ Time Frame: 4 years ]
    Average time from randomization to disease progression (by RECIST 1.1) or death, whichever comes first
  • immune-related Progression Free Survival (irPFS) [ Time Frame: 4 years ]
    Average time from randomization to disease progression (by irRC) or death, whichever comes first.
  • Objective Response Rate (ORR) [ Time Frame: 4 years ]
    Proportion of subjects who achieve a Complete Response (CR) or Partial Response (PR) by RECIST 1.1
  • immune-related Objective Response Rate (irORR) [ Time Frame: 4 years ]
    Proportion of subjects who achieve a Complete Response (CR) or Partial Response (PR) by irRC
  • Best Overall Response (BOR) [ Time Frame: 4 years ]
    Summary of the best response (by RECIST 1.1) achieved by each patient
  • immune-related Best Overall Response (irBOR) [ Time Frame: 4 years ]
    Summary of the best response (by irRC) achieved by each patient
  • Time to Objective Response (TTOR) [ Time Frame: 4 years ]
    Average time from randomization to partial or complete response by RECIST 1.1
  • immune-related Time to Objective Response (irTTOR) [ Time Frame: 4 years ]
    Average time from randomization to partial or complete response by irRC
  • Duration of Response (DOR) [ Time Frame: 4 years ]
    Average time from partial or complete response to disease progression, by RECIST 1.1
  • immune-related Duration of Response (irDOR) [ Time Frame: 4 years ]
    Average time from partial or complete response to disease progression, by irRC
  • Duration of Clinical Benefit (DCB) [ Time Frame: 4 years ]
    Average time from randomization to date of disease progression in subjects achieving a partial or complete response by RECIST 1.1
  • immune-related Duration of Clinical Benefit (irDCB) [ Time Frame: 4 years ]
    Average time from randomization to date of disease progression in subjects achieving a partial or complete response by RECIST 1.1
  • Disease Control Rate (DCR) [ Time Frame: 4 years ]
    Percentage of subjects achieving stable disease or better by RECIST 1.1
  • immune-related Disease Control Rate (irDCR) [ Time Frame: 4 years ]
    Percentage of subjects achieving stable disease or better by irRC
  • Tumor Marker (CA19-9) Kinetics [ Time Frame: 4 years ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Epacadostat, Pembrolizumab, and CRS-207, With or Without CY/GVAX Pancreas in Patients With Metastatic Pancreas Cancer
Official Title  ICMJE Phase 2 Study of Epacadostat, Pembrolizumab, and CRS-207, With or Without Cyclophosphamide and GVAX Pancreas Vaccine in Patients With Metastatic Pancreas Cancer
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Pancreatic Adenocarcinoma
Intervention  ICMJE
  • Drug: Epacadostat
    50, 100, 300, or 600 mg taken by mouth twice a day, every day of each cycle
    Other Name: INCB024360
  • Drug: Pembrolizumab
    200 mg IV on Day 1 of each cycle
    Other Names:
    • MK-3475
    • anti-PD-1 mAb
  • Biological: CRS-207
    1x10^9 CFU given IV on Day 2 of Cycles 3-6 (Arm A) or Day 2 of Cycles 1-6 (Arm B)
  • Drug: CY
    200 mg/m^2 given IV on Day 1 of Cycles 1-2 (Arm A only)
    Other Names:
    • cyclophosphamide
    • cytoxan
  • Biological: GVAX
    5x10^8 cells given as 6 intradermal injections on Day 2 of Cycles 1-2 (Arm A only)
    Other Names:
    • GVAX Pancreas Vaccine
    • Panc 10.05 pcDNA-1/GM-Neo, Panc 6.03 pcDNA-1/GM-Neo
Study Arms  ICMJE
  • Experimental: Epacadostat/Pembrolizumab/CY/GVAX/CRS-207
    Interventions:
    • Drug: Epacadostat
    • Drug: Pembrolizumab
    • Biological: CRS-207
    • Drug: CY
    • Biological: GVAX
  • Experimental: Epacadostat/Pembrolizumab/CRS-207
    Interventions:
    • Drug: Epacadostat
    • Drug: Pembrolizumab
    • Biological: CRS-207
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 15, 2021)
44
Original Estimated Enrollment  ICMJE
 (submitted: December 28, 2016)
70
Estimated Study Completion Date  ICMJE February 2022
Estimated Primary Completion Date February 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Trish Brothers, R.N. 410-614-3644 GIClinicalTrials@jhmi.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03006302
Other Study ID Numbers  ICMJE J16173
IRB00118520 ( Other Identifier: JHMIRB )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study Sponsor  ICMJE Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators  ICMJE Merck Sharp & Dohme Corp.
Investigators  ICMJE
Principal Investigator: Dung Le, M.D. The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
PRS Account Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Verification Date August 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP