FOLFIRINOX Followed by Ipilimumab With Pancreatic Tumor Vaccine in Treatment of Metastatic Pancreatic Cancer

Study Overview
=================
Brief Summary
-----------------
This study will enroll patients who have metastatic pancreatic cancer with stable disease on FOLFIRINOX chemotherapy. The main purpose of this study is to compare survival between patients that receive ipilimumab and a pancreatic tumor vaccine and patients who continue to receive FOLFIRINOX. Funding Source - FDA Office of Orphan Product Development (OOPD)

Official Title
-----------------
A Phase 2, Multicenter Study of FOLFIRINOX Followed by Ipilimumab in Combination With Allogeneic GM-CSF Transfected Pancreatic Tumor Vaccine in the Treatment of Metastatic Pancreatic Cancer

Conditions
-----------------
Metastatic Pancreatic Adenocarcinoma

Intervention / Treatment
-----------------
* Drug: Ipilimumab
* Biological: Vaccine
* Drug: FOLFIRINOX


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria (abbreviated): Documented adenocarcinoma of the pancreas Stable metastatic pancreatic cancer after 8-12 doses of FOLFIRINOX Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Life expectancy greater than 3 months Adequate organ and marrow function defined by study-specified laboratory tests. Must use acceptable form of birth control while on study Oxygen saturation on room air >92% Exclusion Criteria (abbreviated): Surgery within 4 weeks of dosing investigational agent (some exceptions for minor procedures) Off FOLFIRINOX treatment for more than 70 days prior to treatment on study Prior chemotherapy for metastatic pancreatic cancer (other than FOLFIRINOX or adjuvant therapy). History of prior treatment with ipilimumab, anti-PD1 antibody, CD137 agonist, or anti-CD40 antibody Received any non-oncology live vaccine therapy up to one month prior to or after any dose of ipilimumab/vaccine Receiving any other investigational agents Any of the following concomitant therapy: IL-2, interferon, immunosuppressive agents, or chronic use of systemic corticosteroids History of symptomatic autoimmune disease or immune impairment. Thyroid disease is allowed. Known brain metastasis Radiographic ascites that is apparent on physical exam or requiring intervention in the 2 months prior to enrollment Uncontrolled intercurrent illness Known or suspected hypersensitivity to GM-CSF Chronic HIV, Hepatitis B or Hepatitis C Pregnant or breastfeeding women

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: Ipilimumab + Vaccine (Arm A)<br>Ipilimumab and vaccine will be administered every 3 weeks for 4 doses, then every 8 weeks. | Drug: Ipilimumab<br>* 3 mg/kg administered IV (10mg/kg if treatment started prior to protocol v 6.3)<br>* Other names: BMS-734016;Biological: Vaccine<br>* 5x10^8 cells administered in 6 intradermal injections<br>* Other names: Allogeneic GM-CSF-Transduced Pancreatic Tumor Cell Vaccine (GVAX);|
| Experimental: FOLFIRINOX (Arm B)<br>Administered every 14 days (one cycle) | Drug: FOLFIRINOX<br>* Standard of care FOLFIRINOX may be modified according to the patient's known tolerability. Acceptable modified options could include 5-FU alone, capecitabine, FOLFOX, FOLFIRI, or FOLFIRINOX on a 21 day cycle.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Overall Survival is the time between the date of randomization on study and death. | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity of Ipilimumab in Combination With Pancreatic Tumor Vaccine | Toxicity was assessed as the number of patients experiencing study drug-related adverse events (AEs). Data reported for only study drug-related adverse events (not all adverse events as reported in the adverse events section). | From the first dose of study drug through 70 days after last dose, up to 13 months | 
| Progression Free Survival (PFS) | Progression Free Survival is the time from date of randomization to progression or death, whichever comes first. Individuals without follow-up scans were censored one day after randomization and individuals with follow-up scans who did not have disease progression were censored at date of last scan. | Up to 4 years | 
| Immune-related Progression Free Survival (irPFS) | Immune-related Progression Free Survival is the median time from date of randomization to disease progression or death, whichever comes first. Individuals without follow-up scans were censored one day after randomization and individuals with follow-up scans who did not have disease progression were censored at date of last scan. Disease progression was evaluated using immune-related Response Criteria (irRC). irRC differs from RECIST primarily in that target lesions are measured in 2 dimensions and new lesions contribute to tumor burden, but do not by themselves qualify as progressive disease. | Up to 4 years | 
| Objective Response Rate | Objective Response Rate (ORR) is defined as the number of patients from each group achieving a Complete Response (CR) or Partial Response (PR) by Response Evaluation Criteria In Solid Tumors (RECIST). | Assessed until disease progression, up to 2 years | 
| Immune-related Objective Response Rate | Immune-related Objective Response Rate (irORR) is measured the same way, except that tumor responses are evaluated using immune-related response criteria (irRC). irRC differs from RECIST primarily in that target lesions are measured in 2 dimensions and new lesions contribute to tumor burden, but do not by themselves qualify as progressive disease. | Assessed until disease progression, up to 2 years | 
| Duration of Response | Average length of time between achieving a complete response (CR) or partial response (PR) and documentation of recurrent or progressive disease. | Up to 22 months | 
| Tumor Marker Kinetics as Assessed by Median Carbohydrate Antigen 19-9 (CA19-9) Levels | Carbohydrate Antigen 19-9 (CA19-9) is a tumor marker measured in the blood of patients with pancreas cancer. Not all patients with pancreas cancer will have elevated CA19-9 and there are some conditions other than cancer that can cause an elevated CA19-9. Normal CA19-9 range is 0-36 U/mL. | Baseline, Week 7, and Week 10 visits | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Vaccine, Immunotherapy, Ipilimumab, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), antibody, FOLFIRINOX, Pancreatic Cancer