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Safety and Efficacy of Combination Listeria/GVAX Pancreas Vaccine in the Pancreatic Cancer Setting (ECLIPSE)

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ClinicalTrials.gov Identifier: NCT02004262
Recruitment Status : Completed
First Posted : December 9, 2013
Results First Posted : May 3, 2018
Last Update Posted : June 4, 2018
Sponsor:
Collaborator:
Johns Hopkins University
Information provided by (Responsible Party):
Aduro Biotech, Inc.

Brief Summary:
Test the safety, immune response and efficacy of GVAX pancreas vaccine (with cyclophosphamide) and CRS-207 compared to chemotherapy or CRS-207 alone in adults with previously treated metastatic pancreatic adenocarcinoma

Condition or disease Intervention/treatment Phase
2nd-line, 3rd-line and Greater Metastatic Pancreatic Cancer Biological: GVAX Pancreas Vaccine Biological: CRS-207 Drug: Chemotherapy Drug: cyclophosphamide Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 303 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2B, Randomized, Controlled, Multicenter, Open-Label Study of the Efficacy and Immune Response of GVAX Pancreas Vaccine (With Cyclophosphamide) and CRS 207 Compared to Chemotherapy or to CRS-207 Alone in Adults With Previously-Treated Metastatic Pancreatic Adenocarcinoma
Actual Study Start Date : February 5, 2014
Actual Primary Completion Date : January 2016
Actual Study Completion Date : August 23, 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Primary Cohort: Cy/GVAX + CRS-207
  • 200 mg per square meter (mg/m^2) cyclophosphamide (Cy) administered by intravenous (IV) infusion on Day 1 of Weeks 1 and 4; GVAX pancreas vaccine (GVAX, 5 × 10e8 cells) administered by intradermal injection on Day 2 of Weeks 1 and 4; CRS-207 (1 × 10e9 colony forming units [CFU]) administered by IV infusion on Day 1 of Weeks 7, 10, 13, 16.
  • The Primary Cohort comprised those subjects who failed at least 1 gemcitabine-based regimen administered for pancreatic cancer in any setting and failed at least 2 prior chemotherapy regimens administered for pancreatic cancer in the metastatic setting.
Biological: GVAX Pancreas Vaccine
Other Name: GVAX

Biological: CRS-207
Drug: cyclophosphamide
Other Name: Cytoxan

Experimental: Primary Cohort: CRS-207
  • CRS-207 (1 × 10e9 CFU) administered by IV infusion on Day 1 of Weeks 1, 4, 7, 10, 13, 16.
  • The Primary Cohort comprised those subjects who failed at least 1 gemcitabine-based regimen administered for pancreatic cancer in any setting and failed at least 2 prior chemotherapy regimens administered for pancreatic cancer in the metastatic setting.
Biological: CRS-207
Active Comparator: Primary Cohort: Chemotherapy
  • Investigator's choice of one of the following: gemcitabine (1000 mg/m^2) administered by IV infusion on Days 1, 8, and 15 of a 28-day cycle; capecitabine (1000 mg/m^2) administered orally twice a day on Days 1 through 14 of a 21-day cycle; fluorouracil with or without leucovorin (2400 mg^m2) administered by IV infusion over 46 hours on Days 1 and 15 of a 28-day cycle; irinotecan (150 mg/m^2) administered by IV infusion on Days 1 and 15 of a 28-day cycle; or erlotinib (100 mg) administered orally once a day for a 21-day cycle.
  • The Primary Cohort comprised those subjects who failed at least 1 gemcitabine-based regimen administered for pancreatic cancer in any setting and failed at least 2 prior chemotherapy regimens administered for pancreatic cancer in the metastatic setting.
Drug: Chemotherapy
Investigator's choice of one of the following commercially available products: gemcitabine; capecitabine; fluorouracil with or without leucovorin; irinotecan; or erlotinib.

Experimental: 2nd-line Cohort: Cy/GVAX + CRS-207
  • 200 mg/m^2 Cy administered by IV infusion on Day 1 of Weeks 1 and 4; GVAX pancreas vaccine (5 × 10e8 cells) administered by intradermal injection on Day 2 of Weeks 1 and 4; CRS-207 (1 × 10e9 CFU) administered by IV infusion on Day 1 of Weeks 7, 10, 13, 16.
  • The 2nd-line Cohort comprised those subjects who received and failed 1 prior chemotherapy regimen administered for pancreatic cancer in the metastatic setting.
Biological: GVAX Pancreas Vaccine
Other Name: GVAX

Biological: CRS-207
Drug: cyclophosphamide
Other Name: Cytoxan

Experimental: 2nd-line Cohort: CRS-207
  • CRS-207 (1 × 10e9 CFU) administered by IV infusion on Day 1 of Weeks 1, 4, 7, 10, 13, 16.
  • The 2nd-line Cohort comprised those subjects who received and failed 1 prior chemotherapy regimen administered for pancreatic cancer in the metastatic setting.
Biological: CRS-207
Active Comparator: 2nd-line Cohort: Chemotherapy
  • Investigator's choice of one of the following: gemcitabine (1000 mg/m^2) administered by IV infusion on Days 1, 8, and 15 of a 28-day cycle; capecitabine (1000 mg/m^2) administered orally twice a day on Days 1 through 14 of a 21-day cycle; fluorouracil with or without leucovorin (2400 mg^m2) administered by IV infusion over 46 hours on Days 1 and 15 of a 28-day cycle; irinotecan (150 mg/m^2) administered by IV infusion on Days 1 and 15 of a 28-day cycle; or erlotinib (100 mg) administered orally once a day for a 21-day cycle.
  • The 2nd-line Cohort comprised those subjects who received and failed 1 prior chemotherapy regimen administered for pancreatic cancer in the metastatic setting.
Drug: Chemotherapy
Investigator's choice of one of the following commercially available products: gemcitabine; capecitabine; fluorouracil with or without leucovorin; irinotecan; or erlotinib.




Primary Outcome Measures :
  1. Primary Cohort: Overall Survival (OS) Censored at 138 Deaths (ITT Set) [ Time Frame: Subjects were followed from date of randomization to the date of death by any cause, whichever came first, assessed up to 32 months. Analysis conducted when 138 deaths reached in the Primary Cohort in the FAS. ]
    OS was estimated using Kaplan-Meier (KM) methods with 95% confidence intervals (CIs), with censoring at the date when 138 deaths were reached in the Primary Cohort in the FAS. Subjects without documentation of death at the time of final analysis were censored as of the date the subject was last known to be alive on/prior to the primary analysis data cut.

  2. Primary Cohort: OS (All Data, FAS) [ Time Frame: Subjects followed for survival from date of randomization until lost to follow-up, withdrawal of consent, or death, whichever came first, assessed up to 32 months. ]
    For all treated subjects, OS was calculated using KM methods with 95% CIs. Subjects without documentation of death at the time of the analysis were censored as of the date the subject was last known to be alive on/prior to the final analysis data cut.

  3. 2nd-line Cohort: OS (All Data, FAS) [ Time Frame: Subjects followed for survival from date of randomization until lost to follow-up, withdrawal of consent, or death, whichever came first, assessed up to 32 months. ]
    For all treated subjects, OS was calculated using KM methods with 70% CIs. Subjects without documentation of death at the time of the analysis were censored as of the date the subject was last known to be alive on/prior to the final analysis cut. 70% CIs were selected to provide an 80% probability to rule out differences in median survival less than -2.4 months between the 2nd-line Cohort: Chemotherapy arm and the 2nd-line Cohort: Cy/GVAX + CRS-207 and 2nd-line Cohort: CRS-207 arms, based upon the assumptions made in the statistical analysis plan (SAP).


Secondary Outcome Measures :
  1. Number of Participants With Adverse Events in Each Treatment Arm Treatment Regimen [ Time Frame: From the start of the first study drug administration on Day 1, Week 1, through 28 days after the last study drug dose, assessed up to 32 months from the date of randomization. ]
    Safety was assessed based upon the number of adverse events (AEs) that occurred in the FAS of each treatment arm, including serious AEs and total AEs. Total AEs included both serious and non-serious AEs.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Have histologically proven malignant adenocarcinoma of the pancreas; measurable disease is not required, mixed histology is not allowed; subjects must have metastatic disease
  • 2nd line, 3rd line or greater
  • At least 18 years of age
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  • Anticipated life expectancy >12 weeks
  • For women and men of childbearing potential, a medically acceptable method of highly effective contraception (oral hormonal contraceptive, condom plus spermicide, or hormone implants) must be used throughout the study period and for 28 days after their final vaccine administration. A barrier method of contraception must be employed by all subjects (male and female), regardless of other methods.
  • Have adequate organ function as defined by specified laboratory values

Exclusion Criteria:

  • Allergy to both penicillin & sulfa or suspected hypersensitivity to granulocyte-macrophage colony stimulating factor (GM-CSF), dimethyl sulfoxide, fetal bovine serum, trypsin, yeast, glycerol or other component of the therapy options
  • Known history or evidence of brain metastases, immunodeficiency disease or immunocompromised state or history of autoimmune disease requiring systemic steroids or other immunosuppressive treatment
  • Have any evidence of hepatic cirrhosis or clinical or radiographic ascites
  • Have prosthetic heart valves, major implant or device placed in the last 12 months or history of infection with implant/device that cannot be easily removed
  • Rapidly progressing disease
  • Clinically significant and/or malignant pleural effusion
  • Received prior GVAX pancreas vaccine or CRS-207
  • Major surgery or significant traumatic injury (or unhealed surgical wounds) occurring within 28 days prior to receiving study drug, or planned surgery requiring general anesthesia
  • Infection with HIV or hepatitis B or C at screening
  • Valvular heart disease that requires antibiotic prophylaxis for prevention of endocarditis
  • Pregnant or breastfeeding
  • Unable to avoid close contact with another individual known to be at high risk of listeriosis (e.g., newborn infant, pregnant woman, HIV-positive individual) during the course of CRS-207 treatment until completion of antibiotic regimen
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02004262


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Sponsors and Collaborators
Aduro Biotech, Inc.
Johns Hopkins University

Additional Information:
Publications:

Responsible Party: Aduro Biotech, Inc.
ClinicalTrials.gov Identifier: NCT02004262     History of Changes
Other Study ID Numbers: ADU-CL-04
First Posted: December 9, 2013    Key Record Dates
Results First Posted: May 3, 2018
Last Update Posted: June 4, 2018
Last Verified: May 2018

Keywords provided by Aduro Biotech, Inc.:
cancer
cancer vaccine
Listeria monocytogenes
Listeria-based vaccine
GVAX
cyclophosphamide
Cytoxan
immunotherapy
mesothelin

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Vaccines
Gemcitabine
Cyclophosphamide
Fluorouracil
Capecitabine
Irinotecan
Erlotinib Hydrochloride
Pancrelipase
Pancreatin
Immunologic Factors
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents