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”

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.

Study Type: Interventional

Study Design: Treatment, Open Label

Study Primary Completion Date: February 2008

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.

Intervention(s) in this Clinical Trial

• Drug: sargramostim plasmid DNA pancreatic tumor cell vaccine
  • Given subcutaneously

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Stratum I
  • Patients receive booster vaccination comprising allogeneic GM-CSF plasmid DNA pancreatic tumor cell vaccine subcutaneously (SC). Treatment repeats every 6 months.
• Experimental: Stratum II
  • Patients receive priming vaccinations SC once a month for 3 months and then receive booster vaccinations as in stratum I.

Primary Measures

• Safety as measured by local and systemic toxicities
  • Safety Issue?: Yes
• Number, type, and degree of toxicities as measured by NCI CTCAE v3.0
  • Safety Issue?: Yes
• Proportion of patients who experience dose-limiting toxicity within the first 28 days
  • Safety Issue?: Yes

Secondary Measures

• Overall survival
  • Safety Issue?: No
• Recurrence-free survival
  • Safety Issue?: No
• 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
  • Safety Issue?: No
• 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
  • Safety Issue?: No
• Correlation of immune response with clinical response
  • Safety Issue?: No
• 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
  • Safety Issue?: No
• Correlation of PK parameters with clinical outcomes
  • Safety Issue?: No
• Psychosocial profiles (demographics, quality of life [QOL], hope, trust, social support, decision control, & adv. directives) of long-term cancer survivors by EORTC QLQ-C30 v3 at baseline & day 28 of the 1st vacc. and each semiannual vacc.
  • Safety Issue?: No
• Psychosocial profiles of long-term cancer survivors as measured by City of Hope QOL at baseline and day 28 of the first vaccination and each semiannual vaccination
  • Safety Issue?: No
• Psychosocial profiles of long-term cancer survivors as measured by Cancer Patient/Survivor (QOL-CS) Version, and Herth Hope Index at baseline and day 28 of the first vaccination and each semiannual vaccination
  • Safety Issue?: No
• Psychosocial profiles of long-term cancer survivors as measured by Symptom Distress Scale at baseline and day 28 of the first vaccination and each semiannual vaccination
  • Safety Issue?: No
• 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
  • Safety Issue?: No
• Psychosocial profiles of long-term cancer survivors as measured by Pancreatic Cancer Survivor Survey at baseline and day 28 of the first vaccination and each semiannual vaccination
  • Safety Issue?: No
• 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
  • Safety Issue?: No
• Symptom profile (pain, anorexia, fatigue, mood state) by City of Hope QOL at baseline and day 28 of the first vaccination and each semiannual vaccination
  • Safety Issue?: No
• Symptom profile (pain, anorexia, fatigue, mood state) by Cancer Patient/Survivor (QOL-CS) Version at baseline and day 28 of the first vaccination and each semiannual vaccination
  • Safety Issue?: No
• Symptom profile (pain, anorexia, fatigue, mood state) by Herth Hope Index at baseline and day 28 of the first vaccination and each semiannual vaccination
  • Safety Issue?: No
• Symptom profile (pain, anorexia, fatigue, mood state) by Symptom Distress Scale at baseline and day 28 of the first vaccination and each semiannual vaccination
  • Safety Issue?: No
• Symptom profile (pain, anorexia, fatigue, mood state) by Trust Scale at baseline and day 28 of the first vaccination and each semiannual vaccination
  • Safety Issue?: No
• Symptom profile (pain, anorexia, fatigue, mood state) by Pancreatic Cancer Survivor Survey at baseline and day 28 of the first vaccination and each semiannual vaccination
  • Safety Issue?: No
• Clinical activity
  • Safety Issue?: No
• Identification of markers of clinical response
  • Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center

Overall Clinical Trial Officials and Contacts

Daniel A. Laheru, MD Principal Investigator Sidney Kimmel Comprehensive Cancer Center  

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00389610

Study ID Number: CDR0000508892

ClinicalTrials.gov Identifier: NCT00389610

Health Authority: United States: Food and Drug Administration

Clinical trial summary from the National Cancer Institute's PDQ® database