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

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

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)

Study Overview

• Status: Completed
• Conditions: Metastatic Pancreatic Adenocarcinoma
• Intervention / Treatment: Drug: Ipilimumab; Biological: Vaccine; Drug: FOLFIRINOX

• Study Type: Interventional
• Enrollment (Actual): 83
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • UCSF Helen Diller Family Comprehensive Cancer Center
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria (abbreviated):

1. Documented adenocarcinoma of the pancreas
2. Stable metastatic pancreatic cancer after 8-12 doses of FOLFIRINOX
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
4. Life expectancy greater than 3 months
5. Adequate organ and marrow function defined by study-specified laboratory tests.
6. Must use acceptable form of birth control while on study
7. Oxygen saturation on room air >92%

Exclusion Criteria (abbreviated):

1. Surgery within 4 weeks of dosing investigational agent (some exceptions for minor procedures)
2. Off FOLFIRINOX treatment for more than 70 days prior to treatment on study
3. Prior chemotherapy for metastatic pancreatic cancer (other than FOLFIRINOX or adjuvant therapy).
4. History of prior treatment with ipilimumab, anti-PD1 antibody, CD137 agonist, or anti-CD40 antibody
5. Received any non-oncology live vaccine therapy up to one month prior to or after any dose of ipilimumab/vaccine
6. Receiving any other investigational agents
7. Any of the following concomitant therapy: IL-2, interferon, immunosuppressive agents, or chronic use of systemic corticosteroids
8. History of symptomatic autoimmune disease or immune impairment. Thyroid disease is allowed.
9. Known brain metastasis
10. Radiographic ascites that is apparent on physical exam or requiring intervention in the 2 months prior to enrollment
11. Uncontrolled intercurrent illness
12. Known or suspected hypersensitivity to GM-CSF
13. Chronic HIV, Hepatitis B or Hepatitis C
14. Pregnant or breastfeeding women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Ipilimumab + Vaccine (Arm A); Ipilimumab and vaccine will be administered every 3 weeks for 4 doses, then every 8 weeks.	Drug: Ipilimumab; 3 mg/kg administered IV (10mg/kg if treatment started prior to protocol v 6.3); Other Names: BMS-734016; MDX-010; Biological: Vaccine; 5x10^8 cells administered in 6 intradermal injections; Other Names: PANC 6.03 pcDNA-1/GM-Neo and PANC 10.05 pcDNA-1/GM-Neo; Allogeneic GM-CSF-Transduced Pancreatic Tumor Cell Vaccine (GVAX)
EXPERIMENTAL: FOLFIRINOX (Arm B); Administered every 14 days (one cycle)	Drug: FOLFIRINOX; 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.

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

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 1, 2013
• Primary Completion (ACTUAL): May 3, 2019
• Study Completion (ACTUAL): May 3, 2019

Study Registration Dates

• First Submitted: July 8, 2013
• First Submitted That Met QC Criteria: July 8, 2013
• First Posted (ESTIMATE): July 11, 2013

Study Record Updates

• Last Update Posted (ACTUAL): May 19, 2020
• Last Update Submitted That Met QC Criteria: May 5, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: Vaccine; Immunotherapy; antibody; Pancreatic Cancer; Ipilimumab; FOLFIRINOX; cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Vaccines; Ipilimumab; Folfirinox
• Other Study ID Numbers: J13108; NA_00086350 (OTHER: JHMIRB); FD-R-004819-01 (OTHER_GRANT: FDA OOPD)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO