Clinical trial NCT01595321: Pancreatic Tumor Cell Vaccine (GVAX), Cyclophosphamide, SBRT, and FOLFIRINOX in Patients With Resected Adenocarcinoma of the Pancreas
Official title: Pilot Study Evaluating Allogeneic GM-CSF-Transduced Pancreatic Tumor Cell Vaccine (GVAX) and Low Dose Cyclophosphamide With Fractionated Stereotactic Body Radiation Therapy (SBRT) and FOLFIRINOX Chemotherapy in Patients With Resected Adenocarcinoma of the Pancreas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pancreatic Cancer
Keywords: Adjuvant therapy
Immunotherapy
Cytoxan
Cyclophosphamide
Pancreatic Vaccine
Stereotactic radiation therapy
SBRT
FOLFIRINOX
GVAX
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: The Skip Viragh Foundation
First posted: 2012-05-10
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Maximum age (years): 76
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to estimate safety of GVAX Pancreas Vaccine (GVAX) with immune modulating doses of cyclophosphamide (Cy) followed by SBRT and FOLFIRINOX chemotherapy in pancreatic cancer patients after surgery.

Detailed description: This study enrolled patients with surgically resected adenocarcinoma of the pancreas who had titanium clips placed at the time of surgery in order to guide SBRT treatment.

Enrollment was based on traditional 3+3 design with grade 3-4 diarrhea and/or neutropenia defined as the dose limiting toxicity (DLT) within the first 2 cycles (8 weeks) of FOLFIRINOX. The first group of 3 patients (Cohort 1) received SBRT and full dose FOLFIRINOX. The second group of 4 patients (Cohort 2) received SBRT and modified FOLFIRINOX, and the third group of 12 patients (Cohort 3) received SBRT and modified FOLFIRINOX as well as Cy/GVAX vaccinations.

Cy/GVAX (patients 8-19): cyclophosphamide (Cy) at 200 mg/m\^2 intravenously over 30 minutes the day before each vaccine. Each vaccination (GVAX) consists of six total intradermal injections of vaccine, two each in the upper right and left thighs, and two in the upper non-dominant arm. Each injection consists of approximately 2.5x10\^8 cells of each cell line (PANC 6.03/PANC 10.05) for a total of 5x10\^8 cells. The first dose of Cy/GVAX was given within 6-10 weeks from surgery.

Adjuvant SBRT was given 13-17 days after the first dose of Cy/GVAX. Patients receive 5 days of SBRT (6.6 gray (Gy) daily for 33 Gy total) to the tumor bed as delineated by surgical clips placed by the surgeon.

Six 28-day cycles of FOLFIRINOX, starting at least one week after completion of SBRT.

This was permitted to be given locally. Patients were evaluated for dose limiting toxicities (DLTs) within the first 2 cycles (8 weeks).

Cy/GVAX #2-5 was given every 28 days (+/- 3 days), starting 35 days (+/- 7 days) after completion of FOLFIRINOX. Patients without evidence of recurrence could then qualify for additional Cy/GVAX boosts every 6 months (every 12 months with Amendment #10) until disease recurrence, toxicity, withdrawal, or death.

Eligibility criteria: Inclusion Criteria (abbreviated):

1. Documented cancer of the pancreas (head, neck, and/or uncinate process), that has been completely resected
2. No prior Chemotherapy, radiation therapy or biologic therapy for pancreatic cancer
3. Must be within 10 weeks from surgical resection of cancer
4. Titanium clips (minimum 1) must be placed at the time of surgery to aid in SBRT treatment planning
5. ECOG Performance Status of 0 to 1
6. Adequate organ function as defined by study-specified laboratory tests
7. Must use acceptable form of birth control through the study and for 28 days after final dose of study drug
8. Signed informed consent form
9. Willing and able to comply with study procedures

Exclusion criteria (abbreviated):

1. Currently have or have history of certain study-specified heart, liver, kidney, lung, neurological, immune or other medical conditions
2. Presence of metastatic disease
3. 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
4. Systemically active steroids
5. Chemotherapy, radiation therapy or biologic therapy within 28 days prior to receiving study drug
6. Inability to begin protocol treatment within 70 days (10 weeks) after surgery to remove cancer
7. History of HIV, hepatitis B or C infection
8. Pregnant or lactating
9. Conditions, including alcohol or drug dependence, or intercurrent illness that would affect the patient's ability to comply with study visits and procedures

Primary outcomes:
measure: Dose Limiting Toxicities
timeFrame: 8 weeks
measure: Grade 3 or Higher Cy/GVAX-related Adverse Events
timeFrame: 116 months
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: 96 months
measure: Disease-free Survival (DFS)
timeFrame: 96 months
measure: Distant Metastases Free Survival (DMFS)
timeFrame: 96 months
measure: Freedom From Local Progression (FFLP)
timeFrame: 96 months
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
Study officials:
affiliation: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Daniel Laheru, M.D.
role: PRINCIPAL_INVESTIGATOR
References: