A Safety and Efficacy Trial of Lethally Irradiated Allogeneic Pancreatic Tumor Cells Transfected With the GM-CSF Gene in Combination With Adjuvant Chemoradiotherapy for the Treatment of Adenocarcinoma of the Pancreas
18 Years
N/A
Both
Pancreatic Cancer
Trial Information
A Safety and Efficacy Trial of Lethally Irradiated Allogeneic Pancreatic Tumor Cells Transfected With the GM-CSF Gene in Combination With Adjuvant Chemoradiotherapy for the Treatment of Adenocarcinoma of the Pancreas
OBJECTIVES:
Primary
- Determine overall and disease-free survival of patients with resected stage I or II
adenocarcinoma of the pancreas treated with adjuvant chemoradiotherapy in combination
with GVAX pancreatic cancer vaccine.
Secondary
- Correlate specific in vivo parameters of immune response (post-vaccination delayed-type
hypersensitivity reactions to autologous tumor, mesothelin-specific T-cell response,
and the degree of local eosinophil, macrophage, and T-cell infiltration at the vaccine
site) with clinical responses in patients treated with this regimen.
- Determine the toxic effects associated with intradermal injections of this vaccine in
these patients.
OUTLINE: This is an open-label study.
- Post surgery vaccination: Within 8-10 weeks after pancreaticoduodenectomy, patients
receive GVAX pancreatic cancer vaccine intradermally (ID) on day 0.
- Adjuvant chemoradiotherapy: Within 16-28 days after the first vaccination, patients
receive fluorouracil (5-FU) IV continuously for 3 weeks. Approximately 1-2 weeks after
completion of 5-FU, patients receive chemoradiotherapy comprising radiotherapy daily
and 5-FU IV continuously for 26-28 weeks. Approximately 3-5 weeks after completion of
chemoradiotherapy, patients receive 5-FU IV continuously for 4 weeks. 5-FU repeats
every 6 weeks for 2 courses.
- Post chemoradiotherapy vaccination: Within 4-8 weeks after the completion of
chemoradiotherapy, patients receive GVAX pancreatic cancer vaccine ID on days 0, 28,
56, and 196.
Treatment continues in the absence of unacceptable toxicity.
Patients are followed every 3 months for 1 year and then every 6 months thereafter.
PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed invasive ductal adenocarcinoma of the head, neck, and
uncinate process of the pancreas
- Mixed adenocarcinoma tumors allowed if the predominant invasive component of the
tumor is adenocarcinoma
- Stage I or II (clinical stage T1-3, N0-1, M0) disease
- Has undergone pancreaticoduodenectomy at the Johns Hopkins Hospital within the past
8-10 weeks
- Completely resected (R0) or microscopic residual (R1) disease
- No diagnosis other than ductal adenocarcinoma, including any of the following:
- Adenosquamous
- Squamous cell
- Colloid
- Islet cell
- Non-invasive intraductal papillary mucinous neoplasms
- Serous or mucinous cystadenoma or cystadenocarcinoma
- Carcinoid
- Small or large cell carcinoma
- Intraductal oncocytic papillary neoplasms
- Osteoclast-like giant cell tumors
- Acinar cell carcinoma
- Pancreatoblastoma
- Solid pseudopapillary tumors
- Undifferentiated small cell carcinoma
- Non-epithelial tumors (sarcoma, gastrointestinal stromal tumor, or lymphoma)
- Adenocarcinoma of the ampulla
- Adenocarcinoma of the distal bile duct
- Adenocarcinoma of the duodenum
- No recurrent disease
- No metastatic disease, including peritoneal implants or liver and/or lung involvement
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- ECOG 0-1
Life expectancy
- Not specified
Hematopoietic
- Absolute neutrophil count >/= 1,500/mm^3
- Platelet count >/= 100,000/mm^3
- Hemoglobin >/= 10 g/dL
Hepatic
- Bilirubin
- AST/ALT
- Alkaline phosphatase
Renal
- Creatinine
Pulmonary
- No asthma or chronic obstructive pulmonary disease requiring systemic corticosteroids
Immunologic
- HIV negative
- No active infection
- No prior or concurrent autoimmune disease requiring treatment with systemic
immunosuppressants, including any of the following:
- Inflammatory bowel disease
- Systemic vasculitis
- Scleroderma
- Psoriasis
- Multiple sclerosis
- Hemolytic anemia or immune thrombocytopenia
- Rheumatoid arthritis
- Systemic lupus erythematosus
- Sjogren's syndrome
- Sarcoidosis
- Negative results to viral delayed-type hypersensitivity serology testing if
autologous tumor cells are available
Other
- No postoperative complications (e.g., inability to take oral nutrition >/= 1,500
calories/day, ongoing requirement for long-term biliary stenting, or persistence of
wound infection)
- No other malignancy within the past 5 years except nonmelanoma skin cancer
- No uncontrolled medical conditions that would preclude study participation
- No other major active medical or psychosocial problem that could be exacerbated by
study treatment
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for at least 4 weeks
after study participation
PRIOR CONCURRENT THERAPY:
Biologic therapy
- More than 1 month since prior biologic therapy
- No other concurrent biologic therapy, immunotherapy, or gene therapy for pancreatic
cancer
Chemotherapy
- More than 1 month since prior chemotherapy
- No other concurrent chemotherapy for pancreatic cancer
Endocrine therapy
- More than 28 days since prior systemic steroids
- No concurrent systemic corticosteroids
Radiotherapy
- More than 1 month since prior radiotherapy
- No other concurrent radiotherapy for pancreatic cancer
Surgery
- See Disease Characteristics
- Recovered from prior surgery
Other
- More than 1 month since prior participation in an investigational new drug trial
- No other concurrent investigational therapy for pancreatic cancer
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Estimate overall survival and disease-free survival in patients treated with adjuvant chemoradiotherapy in sequence with the irradiated allogeneic GM-CSF transfected pancreatic tumor cell lines versus chemoradiotherapy alone.
Outcome Time Frame:
Continuous
Safety Issue:
No
Principal Investigator
Daniel A. Laheru, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Sidney Kimmel Comprehensive Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
J9988
NCT ID:
NCT00084383
Start Date:
January 2002
Completion Date:
December 2005
Related Keywords:
- Pancreatic Cancer
- stage I pancreatic cancer
- stage II pancreatic cancer
- duct cell adenocarcinoma of the pancreas
- Adenocarcinoma
- Adenocarcinoma, Mucinous
- Pancreatic Neoplasms
Name | Location |
|---|---|
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore, Maryland 21231-2410 |
