Vaccine Therapy in Treating Patients With Pancreatic Cancer That Has Been Removed by Surgery

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00389610
First received: October 18, 2006
Last updated: January 8, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Pancreatic Cancer
Biological: allogenic GM-CSF plasmid-transfected pancreatic tumor cell vaccine
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:
  • Safety as measured by local and systemic toxicities [ Time Frame: Until progression ] [ Designated as safety issue: Yes ]
    Patients continue to receive vaccines until disease progression


Secondary Outcome Measures:
  • Overall survival [ Time Frame: time of first vaccine until death ] [ Designated as safety issue: No ]
  • Recurrence-free survival [ Time Frame: the time from the first vaccine until evidence of disease recurrence ] [ Designated as 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 [ Time Frame: will be computed for each patient at two time points around each vaccine boost: pre-vaccination and four weeks post vaccination ] [ Designated as 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 [ Time Frame: . Autologous lymphocytes will be obtained from peripheral blood before each vaccination, and at four weeks following each vaccinations. ] [ Designated as safety issue: No ]
  • Correlation of immune response with clinical response [ Time Frame: Serum will be obtained from each research participant on days 0 and 3 of treatment. ] [ Designated as 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 [ 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. ] [ Designated as safety issue: No ]
  • 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). ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as 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 [ Time Frame: baseline and day 28 of the first vaccination and each semiannual vaccination ] [ Designated as safety issue: No ]
  • Psychosocial profiles of long-term cancer survivors as measured by Pancreatic Cancer Survivor Survey at baseline [ Time Frame: baseline of the first vaccination ] [ Designated as 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 [ Time Frame: baseline and day 28 of the first vaccination and each semiannual vaccination ] [ Designated as 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 [ Time Frame: baseline and day 28 of the first vaccination and each semiannual vaccination ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]

Enrollment: 56
Study Start Date: September 2006
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Stratum I
Patients receive booster vaccination comprised of an allogenic GM-CSF plasmid-transfected pancreatic tumor cell vaccine, given subcutaneously (SC). Treatment repeats every 6 months.
Biological: allogenic GM-CSF plasmid-transfected pancreatic tumor cell vaccine
Given subcutaneously
Other Name: Panc 10.05 pcDNA1/GM-Neo, Panc 6.03 pcDNA1/GM-Neo
Experimental: Stratum II
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.
Biological: allogenic GM-CSF plasmid-transfected pancreatic tumor cell vaccine
Given subcutaneously
Other Name: Panc 10.05 pcDNA1/GM-Neo, Panc 6.03 pcDNA1/GM-Neo

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00389610

Locations
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Investigators
Principal Investigator: Daniel A. Laheru, MD Sidney Kimmel Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00389610     History of Changes
Other Study ID Numbers: JHOC-J0619, CDR0000508892, P30CA006973, JHOC-J0619, JHOC-SKCCC-J0619, JHOC-00002731, JHOC-GT0604170201, JHOC-0607-799
Study First Received: October 18, 2006
Last Updated: January 8, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
stage I pancreatic cancer
stage II pancreatic cancer
stage III pancreatic cancer
adenocarcinoma of the pancreas

Additional relevant MeSH terms:
Adenocarcinoma
Pancreatic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases

ClinicalTrials.gov processed this record on August 19, 2014