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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
19
Cyclophosphamide (Cy) 200 mg/m\^2 administered one day prior to GVAX (day 0). One dose will be given prior to SBRT and FOLFIRINOX and four additional doses after FOLFIRINOX completion for a total of 5 doses. Additional CY/GVAX boosts may be given every 6 months thereafter until disease recurrence.
GVAX administered one day after Cy (day 1). One dose will be given prior to SBRT and FOLFIRINOX and four additional doses after FOLFIRINOX completion for a total of 5 doses. Additional CY/GVAX boosts may be given every 6 months thereafter until disease recurrence.
Cohort 1 and 2: SBRT (6.6 Gy per day, 33 Gy total dose) will be administered over 5 days within 6-10 weeks of pancreas surgery (Whipple). Cohort 3: SBRT (6.6 Gy) will be administered over 5 days starting between 13-17 days after the first dose of CY/GVAX.
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States
Dose Limiting Toxicities
The number of participants experiencing grade 3-4 diarrhea, neutropenia, and thrombocytopenia within the first 2 cycles (8 weeks) of treatment, regardless of attribution. The rates of each of these toxicities were considered unacceptable if they were 40%, 60%, and 40%, respectively. A decision rule similar to the traditional 3+3 design was used to determine whether it was safe to continue on to the next cohort.
Time frame: 8 weeks
Grade 3 or Higher Cy/GVAX-related Adverse Events
Number of participants with grade 3 or above adverse event attributed to Cy or the GVAX pancreas vaccine. Each adverse event (as defined by NCI CTCAE v4.0) was counted only once for a given subject.
Time frame: 116 months
Overall Survival (OS)
OS was measured as the amount of time from date of surgery until death or end of follow-up. OS was censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis. Estimation based on the Kaplan-Meier curve.
Time frame: 96 months
Disease-free Survival (DFS)
DFS was measured as the time from date of surgery until pancreatic cancer recurrence or death. Disease status was monitored by radiologic scans done approximately every 12 weeks. DFS was censored on the date of last radiologic scan for subjects without documentation of cancer recurrence or death at the time of analysis. Estimation based on the Kaplan-Meier curve.
Time frame: 96 months
Distant Metastases Free Survival (DMFS)
DMFS was measured as the amount of time from date of surgery until metastatic disease progression or death. Metastatic disease progression is the appearance of one or more new lesions outside the primary tumor area (pancreas). Disease status was monitored by radiologic scans done approximately every 12 weeks. DMFS was censored on the date of last radiographic scans for subjects without documentation of metastatic disease progression or death at the time of analysis. Estimation based on the Kaplan-Meier curve.
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FOLFIRINOX is given over six 28-day cycles, starting at least 1 weeks after SBRT. FOLFIRINOX consists of the following drugs given IV on days 1 and 15 of each cycle: Oxaliplatin (85 mg/m\^2), Irinotecan (180 mg/m\^2), Leucovorin (400 mg/m\^2), Fluorouracil (400 mg/m\^2 bolus followed by 2,400 mg/m\^2 continuous infusion over 46-48 hours); modified FOLFIRINOX consists of the same regimen described above but without the 400 mg/m\^2 Fluorouracil bolus.
Time frame: 96 months
Freedom From Local Progression (FFLP)
FFLP was measured as the time from date of surgery until disease recurrence in the pancreas or death. Disease status was monitored by radiologic scans done approximately every 12 weeks. FFLP was censored on the date of last radiographic scans for subjects without documentation of local disease recurrence or death at the time of analysis. Estimation based on the Kaplan-Meier curve.
Time frame: 96 months