Overview

This trial is active, not recruiting.

Condition pancreatic cancer
Treatment allogenic gm-csf plasmid-transfected pancreatic tumor cell vaccine
Phase phase 2
Sponsor Sidney Kimmel Comprehensive Cancer Center
Collaborator National Cancer Institute (NCI)
Start date September 2006
End date December 2017
Trial size 56 participants
Trial identifier NCT00389610, JHOC-00002731, JHOC-0607-799, JHOC-GT0604170201, JHOC-J0619, JHOC-J0619, CDR0000508892, JHOC-SKCCC-J0619, P30CA006973

Summary

RATIONALE: Vaccines made from gene-modified tumor cells may help the body build an immune response to kill tumor cells. Giving booster vaccinations may make a stronger immune response and prevent or delay the recurrence of pancreatic cancer.

PURPOSE: This phase II trial is studying the side effects and how well vaccine therapy works in treating patients with pancreatic cancer that has been removed by surgery.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Patients receive booster vaccination comprised of an allogenic GM-CSF plasmid-transfected pancreatic tumor cell vaccine, given subcutaneously (SC). Treatment repeats every 6 months.
allogenic gm-csf plasmid-transfected pancreatic tumor cell vaccine Panc 10.05 pcDNA1/GM-Neo, Panc 6.03 pcDNA1/GM-Neo
Given subcutaneously
(Experimental)
Patients receive priming vaccinations comprised of allogenic GM-CSF plasmid-transfected pancreatic tumor cell vaccine, given SC once a month for 3 months and then receive booster vaccinations as in stratum I.
allogenic gm-csf plasmid-transfected pancreatic tumor cell vaccine Panc 10.05 pcDNA1/GM-Neo, Panc 6.03 pcDNA1/GM-Neo
Given subcutaneously

Primary Outcomes

Measure
Safety as measured by local and systemic toxicities
time frame: Until progression

Secondary Outcomes

Measure
Overall survival
time frame: time of first vaccine until death
Recurrence-free survival
time frame: the time from the first vaccine until evidence of disease recurrence
Immune response, in terms of mesothelin, prostate stem cell antigen, and mutated k-ras-specific T-cell responses, as measured by biopsy, histological analysis, and in vitro assays at baseline and at 4 weeks post vaccination
time frame: will be computed for each patient at two time points around each vaccine boost: pre-vaccination and four weeks post vaccination
Antitumor immunity, in terms of shared tumor-specific antigens and k-ras-specific antitumor immune responses, as measured at baseline and at 4 weeks post vaccination
time frame: . Autologous lymphocytes will be obtained from peripheral blood before each vaccination, and at four weeks following each vaccinations.
Correlation of immune response with clinical response
time frame: Serum will be obtained from each research participant on days 0 and 3 of treatment.
Correlation of sargramostim (GM-CSF) serum levels with longevity of an allogeneic vaccine as measured by pharmacokinetic (PK) studies at baseline and at day 3
time frame: Serum will be obtained from each research participant on days 0 and 3 of treatment. Pharmacokinetic parameters will be estimated, when possible, using standard compartmental models.
Correlation of PK parameters with clinical outcomes
time frame: The relationship between pharmacokinetic parameters and clinical outcomes will be assessed using logistic regression for binary outcomes (e.g. toxicity) and Cox proportional hazards models for time to event outcomes (e.g. OS, PFS).
Psychosocial profiles (demographics, quality of life [QOL], hope, social support, decision control) and symptom profile (pain, anorexia, fatigue, mood state) as measured by City of Hope QOL, Cancer Patient/Survivor version
time frame: day 0 and day 28 of the each vaccination
Psychosocial profiles of long-term cancer survivors as measured by the Herth Hope Index at baseline and day 28 of the first vaccination and each semiannual vaccination
time frame: baseline and day 28 of the first vaccination and each semiannual vaccination
Psychosocial profiles of long-term cancer survivors as measured by Trust Scale at baseline and day 28 of the first vaccination and each semiannual vaccination
time frame: baseline and day 28 of the first vaccination and each semiannual vaccination
Psychosocial profiles of long-term cancer survivors as measured by Pancreatic Cancer Survivor Survey at baseline
time frame: baseline of the first vaccination
Symptom profile (pain, anorexia, fatigue, mood state) by EORTC QLQ-C30 v3 at baseline and day 28 of the first vaccination and each semiannual vaccination
time frame: baseline and day 28 of the first vaccination and each semiannual vaccination
Symptom profile (pain, anorexia, fatigue, mood state) by Symptom Distress Scale at baseline and day 28 of the first vaccination and each semiannual vaccination
time frame: baseline and day 28 of the first vaccination and each semiannual vaccination
Identification of markers of clinical response
time frame: The CA 19-9 levels will be followed to evaluate whether large and persistent changes might correlate with either in vitro immune responses or with time to clinical recurrence.

Eligibility Criteria

Male or female participants from 18 years up to 120 years old.

DISEASE CHARACTERISTICS: - Confirmed diagnosis of adenocarcinoma of the head, neck, tail, or uncinate of the pancreas meeting the following criteria: - Stage I-III disease - Prior surgical resection required - No radiographic evidence of disease recurrence PATIENT CHARACTERISTICS: - ECOG performance status 0-1 - Hemoglobin ≥ 9 g/dL - Absolute neutrophil count ≥ 1,500/mm³ - Platelet count ≥ 100,000/mm³ - Creatinine ≤ 2.0 mg/dL - Bilirubin ≤ 2.0 mg/dL (unless due to known Gilbert's syndrome) - AST, ALT, and amylase ≤ 2 times upper limit of normal (ULN) - Alkaline phosphatase ≤ 5 times ULN - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception - No other uncontrolled illness - No active, ongoing infection - No history of autoimmune disease (e.g., systemic lupus erythematosus, sarcoidosis, rheumatoid arthritis, glomerulonephritis, or vasculitis) PRIOR CONCURRENT THERAPY: - See Disease Characteristics - At least 28 days since prior anticancer therapy (e.g., adjuvant chemoradiotherapy) - At least 28 days since prior systemic steroid therapy - At least 6 months since last vaccination with sargramostim (GM-CSF) plasmid DNA pancreatic tumor cell vaccine (cell lines Panc 10.05 and Panc 6.03) while enrolled on SKCCC-J9617 or SKCCC-J9988 - No concurrent systemic steroid therapy during and for ≥ 28 days after vaccination - No concurrent radiation therapy - No other concurrent immunotherapy, biologic therapy, or gene therapy

Additional Information

Official title A Safety and Efficacy Trial of Vaccine Boosting With Lethally Irradiated Allogeneic Pancreatic Tumor Cells Transfected With the GM-CSF Gene for the Treatment of Pancreatic Adenocarcinoma
Principal investigator Daniel A. Laheru, MD
Description OBJECTIVES: Primary - Determine the safety of primary and boost vaccinations with lethally irradiated allogeneic pancreatic tumor cells transfected with sargramostim (GM-CSF) gene vaccine in patients with surgically resected adenocarcinoma of the head, neck, or uncinate of the pancreas. Secondary - Correlate specific in vivo parameters of immune response (e.g., mesothelin, prostate stem cell antigen, and mutated k-ras-specific T-cell responses) with clinical response in patients treated with this regimen. - Determine the efficacy, in terms of overall and recurrence-free survival, of this regimen in these patients. - Correlate serum GM-CSF levels with longevity of an allogeneic vaccine after semi-annual boosting in these patients. - Determine the psychosocial (e.g., demographics, quality of life, hope, trust, social support, decision control, and advanced directives) and symptom (e.g., pain, anorexia, fatigue, and mood state) profiles in these patients and explore changes over time. OUTLINE: This is a open-label study. Patients are stratified according to prior vaccination with allogeneic sargramostim (GM-CSF)-secreting pancreatic tumor cell vaccine (yes [stratum I] vs no [stratum II]). - Stratum I: Patients receive booster vaccination comprising allogeneic GM-CSF plasmid DNA pancreatic tumor cell vaccine subcutaneously (SC). Treatment repeats every 6 months in the absence of disease progression or unacceptable toxicity. - Stratum II: Patients receive priming vaccinations SC once a month for 3 months and then receive booster vaccinations as in stratum I. Patients complete self-reported psychosocial (including quality of life, hope, and trust) and symptom (including pain, fatigue, anorexia, and mood) questionnaires at day 0 and day 28. After completion of study treatment, patients are followed at day 28 and then annually for 15 years. PROJECTED ACCRUAL: A total of 100 patients will be accrued for this study.
Trial information was received from ClinicalTrials.gov and was last updated in August 2016.
Information provided to ClinicalTrials.gov by Sidney Kimmel Comprehensive Cancer Center.