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

NCT01595321 | Completed Phase 2 Results DMC

• 2 other identifiers: J1179NA_00050233
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

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.

Conditions

Pancreatic Cancer

Keywords

Adjuvant therapy; Immunotherapy; Cytoxan; Cyclophosphamide; Pancreatic Vaccine; Stereotactic radiation therapy; SBRT; FOLFIRINOX; GVAX

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  116 months

Secondary Outcomes (4)

• Overall Survival (OS)

  96 months

• Disease-free Survival (DFS)

  96 months

• Distant Metastases Free Survival (DMFS)

  96 months

• Freedom From Local Progression (FFLP)

  96 months

Study Arms (3)

Cohort 1: SBRT and FOLFIRINOX

EXPERIMENTAL

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.

Radiation: Stereotactic Body Radiation; Drug: FOLFIRINOX

Cohort 2: SBRT and modified FOLFIRINOX

EXPERIMENTAL

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).

Radiation: Stereotactic Body Radiation; Drug: FOLFIRINOX

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

EXPERIMENTAL

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

Drug: Cyclophosphamide; Biological: GVAX Pancreas Vaccine; Radiation: Stereotactic Body Radiation; Drug: FOLFIRINOX

Interventions

Cyclophosphamide 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.

Also known as: Cytoxan, Cy

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

GVAX Pancreas Vaccine 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.

Also known as: GVAX, PANC 10.05 pcDNA-1/GM-Neo and PANC 6.03 pcDNA-1/GM-Neo vaccine

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

Stereotactic Body Radiation 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.

Also known as: SBRT

Cohort 1: SBRT and FOLFIRINOX; Cohort 2: SBRT and modified FOLFIRINOX; Cohort 3: CY, GVAX, SBRT, and modified FOLFIRINOX

FOLFIRINOX 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 1: SBRT and FOLFIRINOX; Cohort 2: SBRT and modified FOLFIRINOX; Cohort 3: CY, GVAX, SBRT, and modified FOLFIRINOX

Eligibility Criteria

• Age: 18 Years - 76 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• The Skip Viragh Foundation: collaborator

Study Sites (1)

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Cyclophosphamide; Radiosurgery; folfirinox

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Daniel Laheru, MD
• Organization: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Laherda@jhmi.edu

410-955-8974

Study Officials

• Daniel Laheru, M.D.

  The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2012
• First Posted: May 10, 2012
• Study Start: October 29, 2012
• Primary Completion: October 18, 2023
• Study Completion: October 18, 2023
• Last Updated: August 14, 2024
• Results First Posted: August 14, 2024

Record last verified: 2024-07

Locations

US (1)