Ipilimumab +/- Vaccine Therapy in Treating Patients With Locally Advanced, Unresectable or Metastatic Pancreatic Cancer

Study Overview
=================
Brief Summary
-----------------
Research Hypothesis: Ipilimumab (an antibody that blocks negative signals to T cells) administered alone or in combination with a pancreatic cancer vaccine (allogeneic pancreatic tumor cells transfected with a GM-CSF gene), has an acceptable safety profile in subjects with locally advanced, unresectable or metastatic pancreatic adenocarcinoma. Primary Objective: To determine the safety profile of ipilimumab alone or in combination with a pancreatic cancer vaccine in subjects with locally advanced, unresectable or metastatic pancreatic adenocarcinoma. Secondary Objectives: To estimate overall survival (OS) which will serve as the primary efficacy signal. To explore an association of T cell responses and immunological responses with OS in patients receiving treatment. To estimate overall response rate (ORR), immune related best overall response rate (irBOR), progression free survival (PFS), and duration of response in patients receiving treatment. To explore an association between immune-related adverse events (IRAEs) and ORR. To measure tumor marker kinetics (CA 19-9) in patients receiving treatment.

Official Title
-----------------
A Phase Ib Trial Evaluating the Safety and Feasibility of Ipilimumab (BMS-734016) Alone or in Combination With Allogeneic Pancreatic Tumor Cells Transfected With a GM-CSF Gene for the Treatment of Locally Advanced, Unresectable or Metastatic Pancreatic Adenocarcinoma

Conditions
-----------------
Pancreatic Cancer

Intervention / Treatment
-----------------
* Drug: Ipilimumab
* Biological: Pancreatic Cancer Vaccine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Documented cancer of the pancreas who have failed (or are not candidates for) standard therapy ECOG Performance Status of 0 to 1 Adequate organ function as defined by study-specified laboratory tests Must use acceptable form of birth control through the study and for 28 days after final dose of study drug Signed informed consent form Willing and able to comply with study procedures Exclusion Criteria: Currently have or have history of certain study-specified heart, liver, kidney, lung, neurological, immune or other medical conditions Clinical metabolic or laboratory abnormalities defined as Grade 3 or 4 of the National Cancer Institute's (NCI's) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 Systemically active steroids Another investigational product within 28 days prior to receiving study drug Major surgery or significant traumatic injury (or unhealed surgical wounds) occurring within 28 days prior to receiving study drug Infection with HIV, hepatitis B or C at screening Pregnant or lactating Conditions, including alcohol or drug dependence, or intercurrent illness that would affect the patient's ability to comply with study visits and procedures

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: Ipilimumab Alone<br>Ipilimumab alone | Drug: Ipilimumab<br>* Ipilimumab (10mg/kg) will be administered intravenously at weeks 1, 4, 7 and 10. Subjects will also be offered maintenance phase dosing every 12 weeks.<br>* Other names: MDX-010;|
| Experimental: Arm 2: Ipilimumab + Pancreatic Cancer Vaccine<br>Ipilimumab + Pancreatic Cancer Vaccine | Drug: Ipilimumab<br>* Ipilimumab (10mg/kg) will be administered intravenously at weeks 1, 4, 7 and 10. Subjects will also be offered maintenance phase dosing every 12 weeks.<br>* Other names: MDX-010;Biological: Pancreatic Cancer Vaccine<br>* The Pancreatic Cancer Vaccine (5E8 cells) will be administered intradermally at weeks 1, 4, 7 and 10. Subjects will also be offered maintenance phase dosing every 12 weeks.<br>* Other names: PANC 10.05 pcDNA-1/GM-Neo and PANC 6.03 pcDNA-1 neo vaccine;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Patients Experiencing an Unacceptable Toxicity | Unacceptable toxicity is defined as drug related >grade 4 AEs or grade 3 AEs including IRAEs not improving to < grade 2 under therapy within 2 weeks. In addition, > grade 2 eye pain or reduction of visual acuity that does not respond to topical therapy and does not improve to < grade 1 severity within 2 weeks of starting therapy, or requires systemic therapy is an unacceptable toxicity. | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS will be measured from date of randomization until death or end of follow-up (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis). | 4 years | 
| Overall Response Rate (ORR) | ORR is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) during the first 6 months of treatment. CR = disappearance of all target lesions, PR is =>30% decrease in sum of diameters of target lesions, progressive disease (PD) is >20% increase in sum of diameters of target lesions, stable disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions. Estimation based on the Kaplan-Meier curve. | 6 months | 
| Immune Related Best Overall Response Rate (irBOR) | Immune Related Best Overall Response (BOR) is the best response recorded from the start of the study treatment until the disease progression/recurrence based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Estimation based on the Kaplan-Meier curve. | 4 years | 
| Progression Free Survival (PFS) | PFS is defined as the number of months from the date of randomization to disease progression (progressive disease [PD] or relapse from complete response [CR] as assessed using RECIST 1.1 criteria) or death due to any cause. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is >20% increase in sum of diameters of target lesions, Stable Disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions. | 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
antibody, pancreatic cancer, vaccine, immunotherapy, CTLA-4