Safety and Efficacy of Listeria and GVAX in Pancreatic Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Johns Hopkins University
Information provided by (Responsible Party):
Aduro BioTech, Inc.
ClinicalTrials.gov Identifier:
NCT01417000
First received: August 10, 2011
Last updated: January 10, 2014
Last verified: January 2014
  Purpose

This clinical trial will evaluate the safety, immune response and overall survival of the sequential administration of two cancer vaccines, GVAX Pancreas Vaccine and CRS-207. GVAX vaccines are composed of cancer cells that have been genetically-modified to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF) to stimulate the immune system and that have been irradiated to prevent further cell division. GVAX Pancreas is administered with cyclophosphamide, which has been shown to increase effectiveness of GVAX by inhibiting T regulatory cells. CRS-207 is a weakened (attenuated) form of Listeria monocytogenes that has been genetically modified to reduce its capacity to cause disease, while maintaining its ability to stimulate potent innate and adaptive immunity. CRS-207 has been engineered to elicit an immune response against the tumor-associated antigen mesothelin, which has been shown to be present at higher levels on certain tumor cells than on normal cells.


Condition Intervention Phase
Pancreatic Cancer
Drug: GVAX Pancreas, Cyclophosphamide and CRS-207
Drug: GVAX Pancreas and Cyclophosphamide
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2, Randomized, Multicenter, Open-Label Study of the Efficacy and Immune Response of the Sequential Administration of GVAX Pancreas Vaccine Alone or Followed by CRS-207 in Adults With Metastatic Pancreatic Adenocarcinoma

Resource links provided by NLM:


Further study details as provided by Aduro BioTech, Inc.:

Primary Outcome Measures:
  • To compare overall survival in subjects receiving test treatments [ Time Frame: Up to five years ] [ Designated as safety issue: No ]
    Patients will be followed at regular intervals to assess survival


Secondary Outcome Measures:
  • To assess safety of the cyclophosphamide, GVAX Pancreas vaccine, and CRS-207 treatment regimen [ Time Frame: About 2 years ] [ Designated as safety issue: Yes ]
    Patients will be monitored for adverse events throughout the course of the study

  • To assess the immune response [ Time Frame: About three years ] [ Designated as safety issue: No ]
    Patient samples will be evaluated for vaccine-induced Listeria- and mesothelin-specific immune responses


Estimated Enrollment: 90
Study Start Date: September 2011
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vaccine Arm A

60 patients total.

Weeks 1 and 4:

Cyclophosphamide (Day 1) GVAX pancreas vaccine (Day 2)

Weeks 7, 10, 13, and 16:

CRS-207 (Day 1)

Drug: GVAX Pancreas, Cyclophosphamide and CRS-207
Cyclophosphamide (200 mg/m2), GVAX Pancreas vaccine (5 × 10e8 cells), CRS-207 (1 × 10e9 CFU)
Other Name: Cytoxan, GM-CSF, Listeria
Experimental: Vaccine Arm B

30 patients total.

Weeks 1, 4, 7, 10, 13, and 16:

Cyclophosphamide (Day 1) GVAX pancreas vaccine (Day 2)

Drug: GVAX Pancreas and Cyclophosphamide
Cyclophosphamide (200 mg/m2), GVAX pancreas vaccine (5 × 10e8 cells)
Other Name: Cytoxan, GM-CSF

Detailed Description:

This is a Phase 2, randomized, multicenter, open-label study of cyclophosphamide and GVAX pancreas vaccine followed by CRS-207 in adults with metastatic pancreatic adenocarcinoma who have received or refused at least one prior chemotherapy treatment.

Eligible subjects will be randomized in a 2:1 ratio to receive either two doses of cyclophosphamide and GVAX pancreas vaccine and up to 4 doses of CRS-207 at 1 × 10e9 CFU (Treatment Arm A) or up to six doses of cyclophosphamide and GVAX pancreas vaccine (Treatment Arm B). Study assessments include blood draws for safety and immune response monitoring and CT scans for tumor response evaluations.

After completion of treatment, subjects will continue to be followed by phone and optional clinic visits for the duration of the study. At the investigator's discretion, subjects may receive additional cycles of the assigned treatment regimen if they are clinically stable and meet dosing eligibility. At the conclusion of the study, all remaining subjects will be offered enrollment in a long-term follow-up study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Have histologically proven malignant adenocarcinoma of the pancreas; measurable disease is not required. (Subjects with mixed histology will be included if the predominant component is adenocarcinoma. Subjects must have metastatic disease.)
  • Have received or refused at least one chemotherapy regimen
  • Be at least 18 years of age
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Have an anticipated life expectancy of greater than 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.)
  • Be willing and able to give written informed consent, and be able to comply with all study procedures
  • Have adequate organ function as defined by specified laboratory values

Exclusion Criteria:

  • Currently have or have history of certain study-specified heart, liver, kidney, lung, neurological, immune or other medical conditions
  • Have a known history or evidence of brain metastases
  • Have any evidence of hepatic cirrhosis or clinical or radiographic ascites
  • Have clinically significant and/or malignant pleural effusion
  • Known or suspected hypersensitivity to any component of GVAX Pancreas vaccine or CRS-207, or known allergy to both penicillin and sulfa
  • Received an investigational product within 28 days of study treatment or planned to receive within 28 days after vaccine administration
  • Used any systemic steroids within 28 days of study treatment
  • Use more than 3 g/d of acetaminophen
  • An artificial (prosthetic) joint or other artificial implant or device that cannot be easily removed (with some exceptions for dental and breast implants and biliary stents and mediports)
  • 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
  • Any immunodeficiency disease or immunocompromised state or active autoimmune disease or history of autoimmune disease requiring systemic steroids or other immunosuppressive treatment
  • Be a woman who is 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01417000

Locations
United States, Florida
H. Lee Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital
Baltimore, Maryland, United States, 21231
National Cancer Institute
Bethesda, Maryland, United States, 20892
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
United States, New York
Herbert Irving Comprehensive Cancer Center of Columbia University
New York, New York, United States, 10032
NYU Langone Medical Center
New York City, New York, United States, 10016
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Oregon
Providence Portland Medical Center
Portland, Oregon, United States, 97213
United States, Pennsylvania
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15213
United States, Washington
Virginia Mason Medical Center
Seattle, Washington, United States, 98101
Sponsors and Collaborators
Aduro BioTech, Inc.
Johns Hopkins University
Investigators
Principal Investigator: Dung T Le, MD Johns Hopkins University
  More Information

Additional Information:
Publications:
Responsible Party: Aduro BioTech, Inc.
ClinicalTrials.gov Identifier: NCT01417000     History of Changes
Obsolete Identifiers: NCT01468870
Other Study ID Numbers: ADU-CL-01
Study First Received: August 10, 2011
Last Updated: January 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Aduro BioTech, Inc.:
Cancer
Cancer vaccine
Listeria monocytogenes
Listeria-based vaccines
GVAX
Cyclophosphamide
Cytoxan
T regulatory cells
Heterologous Prime-Boost
Immunotherapy
Mesothelin
Pancreatic cancer

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Cyclophosphamide
Pancreatin
Pancrelipase
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Gastrointestinal Agents

ClinicalTrials.gov processed this record on April 16, 2014