Clinical trial NCT02243371: GVAX Pancreas Vaccine (With CY) and CRS-207 With or Without Nivolumab
Official title: A Randomized Phase 2 Study of the Safety, Efficacy, and Immune Response of GVAX Pancreas Vaccine (With Cyclophosphamide) and CRS-207 With or Without Nivolumab in Patients With Previously Treated Metastatic Pancreatic Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Previously Treated Metastatic Adenocarcinoma of the Pancreas
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
name: Stand Up To Cancer
name: Aduro Biotech, Inc.
name: American Association for Cancer Research
name: Lustgarten Foundation
First posted: 2014-09-17
Enrollment: 93
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to compare the overall survival (OS) of subjects with previously treated metastatic pancreatic cancer treated with cyclophosphamide (CY)/nivolumab/GVAX pancreas vaccine followed by nivolumab/CRS-207 (Arm A) to subjects treated with CY/GVAX pancreas vaccine followed by CRS-207 (Arm B).


Eligibility criteria: Inclusion Criteria:

* Age ≥18 years.
* Have histologically- or cytologically-proven adenocarcinoma of the pancreas. Patients with mixed histology will be excluded.
* Have metastatic disease.
* Have failed only 1 prior chemotherapy regimen for metastatic pancreatic cancer.
* Patients with the presence of at least one measurable lesion.
* Patients acceptance to have a tumor biopsy of an accessible lesion at baseline and on treatment if the lesion can be biopsied with acceptable clinical risk (as judged by the investigator).
* ECOG performance status 0 or 1.
* Life expectancy of greater than 3 months.
* Patients must have adequate organ and marrow function defined by study-specified laboratory tests.
* Must use acceptable form of birth control while on study.
* Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

* known history or evidence of brain metastases.
* Had surgery within the last 28 days
* Have received any non-oncology vaccine therapy used for prevention of infectious diseases including seasonal vaccinations within 28 days of study treatment.
* Prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA4, GVAX or CRS-207
* Systemic steroids within the last 14 days
* Use more than 3 g/day of acetaminophen.
* Patients on immunosuppressive agents.
* Patients receiving growth factors within the last 14 days
* Known allergy to both penicillin and sulfa.
* Severe hypersensitivity reaction to any monoclonal antibody.
* Have artificial joints or implants that cannot be easily removed
* Have any evidence of hepatic cirrhosis or clinical or radiographic ascites.
* Have significant and/or malignant pleural effusion
* Infection with HIV or hepatitis B or C at screening
* Significant heart disease
* 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
* Unable to avoid intimate 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.
* Are pregnant or breastfeeding.
* Have rapidly progressing disease

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: 2 years and 7 months
Secondary outcomes:
measure: Number of Patients Experiencing a Grade 3 or Above Treatment-related Toxicity
timeFrame: 2 years and 7 months
measure: Progression-free Survival (PFS) in Metastatic Pancreatic Cancer Patients
timeFrame: 2 years and 7 months
measure: Immune-related Progression-free Survival (irPFS) by IRRC in Metastatic Pancreatic Cancer Patients
timeFrame: 2 years and 7 months
measure: Time to Progression (TTP) by RECIST 1.1 in Metastatic Pancreatic Cancer Patients
timeFrame: 2 years and 7 months
measure: Number of Participants With Partial Response (PR) or Complete Response (CR) as Defined by RECIST 1.1 in Metastatic Pancreatic Cancer Patients
timeFrame: 2 years and 7 months
measure: Tumor Marker Kinetics (CA 19-9) in Patients With Baseline Abnormal Levels as Measured by Number of Participants With Stable or Responding CA19-9 Concentration
timeFrame: 120 days
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: Johns Hopkins University
name: Dung Le, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hopkins AC, Yarchoan M, Durham JN, Yusko EC, Rytlewski JA, Robins HS, Laheru DA, Le DT, Lutz ER, Jaffee EM. T cell receptor repertoire features associated with survival in immunotherapy-treated pancreatic ductal adenocarcinoma. JCI Insight. 2018 Jul 12;3(13):e122092. doi: 10.1172/jci.insight.122092.