Pancreatic Tumor Cell Vaccine (GVAX), Cyclophosphamide, SBRT, and FOLFIRINOX in Patients With Resected Adenocarcinoma of the Pancreas

NCT ID: NCT01595321

Last Updated: 2024-08-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-29
• Study Completion Date: 2023-10-18

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.

Conditions

Pancreatic Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1: SBRT and FOLFIRINOX

The initial 3 patients were treated with SBRT and full dose FOLFIRINOX and observed for the first 2 cycles (8 weeks) for dose limiting toxicities (DLTs). If 2-3 patients are observed with uncontrolled grade 3-4 diarrhea, 2-3 patients are observed with grade 3-4 thrombocytopenia, or if 3 patients are observed with grade 3-4 neutropenia within the first 2 cycles of FOLFIRINOX administration (8 weeks) then the dose level will be deemed unacceptable.

Group Type: EXPERIMENTAL

Stereotactic Body Radiation

Intervention Type: RADIATION

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.

FOLFIRINOX

Intervention Type: DRUG

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.

Cohort 2: SBRT and modified FOLFIRINOX

The next 4 patients were treated with SBRT and modified FOLFIRINOX and observed for the first 2 cycles (8 weeks) for dose limiting toxicities (DLTs). If no patients are observed with grade 3-4 diarrhea, thrombocytopenia, or neutropenia, then the next cohort of patients will receive SBRT, modified FOLFIRINOX, and GVAX (with Cy).

Group Type: EXPERIMENTAL

Stereotactic Body Radiation

Intervention Type: RADIATION

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.

FOLFIRINOX

Intervention Type: DRUG

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.

Cohort 3: CY, GVAX, SBRT, and modified FOLFIRINOX

The last 12 patients will receive Cy, GVAX, SBRT, and modified FOLFIRINOX.

Group Type: EXPERIMENTAL

Cyclophosphamide

Intervention Type: DRUG

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 Pancreas Vaccine

Intervention Type: BIOLOGICAL

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.

Stereotactic Body Radiation

Intervention Type: RADIATION

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.

FOLFIRINOX

Intervention Type: DRUG

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.

Interventions

Cyclophosphamide

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.

Intervention Type: DRUG

GVAX Pancreas Vaccine

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.

Intervention Type: BIOLOGICAL

Stereotactic Body Radiation

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.

Intervention Type: RADIATION

FOLFIRINOX

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.

Intervention Type: DRUG

Other Intervention Names

Cytoxan; Cy; GVAX; PANC 10.05 pcDNA-1/GM-Neo and PANC 6.03 pcDNA-1/GM-Neo vaccine; SBRT

Eligibility Criteria

Inclusion Criteria

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

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 76 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Skip Viragh Foundation

OTHER

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Daniel Laheru, M.D.

Role: PRINCIPAL_INVESTIGATOR

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Locations

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NA_00050233

Identifier Type: OTHER

Identifier Source: secondary_id

J1179

Identifier Type: -

Identifier Source: org_study_id