Safety and Efficacy of Combination Listeria/GVAX Immunotherapy in Pancreatic Cancer

Study Overview
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Brief Summary
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Test the safety, immune response and efficacy of GVAX pancreas vaccine (with cyclophosphamide) and CRS-207 compared to GVAX pancreas vaccine (with cyclophosphamide) alone in adults who have failed or refused prior treatment for metastatic pancreatic cancer.

Official Title
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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

Conditions
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Metastatic Pancreatic Cancer

Intervention / Treatment
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* Biological: GVAX Pancreas
* Biological: CRS-207
* Drug: Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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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 At least 18 years of age Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Anticipated life expectancy of >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 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 Prosthetic joint or other artificial implant or device that cannot be easily removed (there are some exceptions) 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 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cy/GVAX + CRS-207<br>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. | Biological: GVAX Pancreas<br> <br> * Other names: GVAX;Biological: CRS-207<br> <br> Drug: Cyclophosphamide<br> <br> * Other names: Cy;|
| Experimental: Cy/GVAX<br>200 mg/m^2 Cy administered by IV infusion on Day 1 of Weeks 1, 4, 7, 10, 13, 16; GVAX (5 × 10e8 cells) administered by intradermal injection on Day 2 of Weeks 1, 4, 7, 10, 13, 16. | Biological: GVAX Pancreas<br> <br> * Other names: GVAX;Drug: Cyclophosphamide<br> <br> * Other names: Cy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) in Subjects Receiving Test Treatments (FAS) | For all treated subjects, OS was defined as the time between the date of randomization and the date of death or censoring, and was estimated using Kaplan-Meier (KM) methods with 95% confidence intervals (CIs). Subjects without documentation of death at the time of the final analysis were censored using the date the subject was last known to be alive. Per the study protocol, following an Interim Analysis (IA), subjects in the Cy/GVAX arm were offered rollover to Cy/GVAX + CRS-207 arm. 3 subjects rolled over to the Cy/GVAX + CRS-207 arm (rollover subjects). These rollover subjects were censored at the day prior to the first rollover treatment dose date, and were included for analysis in the Cy/GVAX arm. Additionally, 2 subjects originally treated per the Cy/GVAX + CRS-207 arm discontinued treatment and entered follow-up, but following IA were re-treated per the Cy/GVAX + CRS-207 arm regimen. Data from these re-treated subjects were included in the Cy/GVAX + CRS-207 arm analysis. | Subjects were followed from the date of randomization to the date of death or discontinuation, whichever came first, assessed up to 60 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Assess Safety of the Cyclophosphamide, GVAX Pancreas Vaccine, and CRS-207 Treatment Regimen | 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. AEs reported for the Cy/GVAX + CRS-207 arm (FAS) include the 61 treated subjects initially assigned to this arm plus AEs occurring on/after the first rollover dose date for the 3 Cy/GVAX rollover subjects. AEs reported for the Cy/GVAX arm (FAS) include treated subjects initially assigned to this arm but exclude AEs for rollover subjects occurring on/after the first rollover dose date. | Starting with administration of first investigational drug product through 28 days after final study treatment, assessed up to 60 months from the date of randomization. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer, Cancer vaccine, Listeria monocytogenes, Listeria-based vaccines, GVAX, Cyclophosphamide, Cytoxan, T regulatory cells, Heterologous Prime-Boost, Immunotherapy, Mesothelin, Pancreatic cancer