Vaccine Therapy Combined With Adjuvant Chemoradiotherapy In Treating Patients With Resected Stage I Or Stage II Adenocarcinoma (Cancer) Of The Pancreas

Study Overview

Vaccine Therapy Combined With Adjuvant Chemoradiotherapy in Treating Patients With Resected Stage I or Stage II Adenocarcinoma (Cancer) of the Pancreas

RATIONALE: Vaccines made from gene-modified pancreatic cancer cells may make the body build an immune response to kill tumor cells. Drugs used in chemotherapy, such as fluorouracil, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Giving vaccine therapy together with chemotherapy and radiation therapy after surgery may kill any remaining tumor cells. PURPOSE: This phase II trial is studying how well giving vaccine therapy together with adjuvant chemoradiotherapy works in treating patients with resected stage I or stage II adenocarcinoma (cancer) 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.

Pancreatic Cancer

BIOLOGICAL: GVAX pancreatic cancer vaccine

J9988
R01CA088058 (U.S. NIH Grant/Contract)
P30CA006973 (U.S. NIH Grant/Contract)
JHOC-J9988

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2004-06-10	Results First Submitted 2013-03-01	Last Update Submitted that met QC Criteria 2013-07-17
First Submitted that Met QC Criteria 2004-06-10	Results First Submitted that Met QC Criteria 2013-06-10	Last Update Posted (ESTIMATED) 2013-07-22
First Posted (ESTIMATED) 2004-06-11	Results First Posted 2013-07-15	Last Verified 2013-07

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: GVAX pancreatic cancer vaccine 5E8 vaccine cells. The first vaccination is administered 6-8 weeks after surgery. Four to eight weeks following the completion of the last cycle of adjuvant radiation and chemotherapy (chemo-radiation therapy is standard of care and not part of the protoc	BIOLOGICAL: GVAX pancreatic cancer vaccine Patients will receive vaccinations consisting of 5E8 vaccine cells. The first vaccination is administered 6-8 weeks after surgery. Four to eight weeks following the completion of the last cycle of adjuvant radiation and chemotherapy (chemo-radiation thera

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: GVAX pancreatic cancer vaccine

5E8 vaccine cells. The first vaccination is administered 6-8 weeks after surgery. Four to eight weeks following the completion of the last cycle of adjuvant radiation and chemotherapy (chemo-radiation therapy is standard of care and not part of the protoc

BIOLOGICAL: GVAX pancreatic cancer vaccine

Patients will receive vaccinations consisting of 5E8 vaccine cells. The first vaccination is administered 6-8 weeks after surgery. Four to eight weeks following the completion of the last cycle of adjuvant radiation and chemotherapy (chemo-radiation thera

Primary Outcome Measures	Measure Description	Time Frame
Overall Survival	Overall survival in patients treated with adjuvant chemoradiotherapy in sequence with the irradiated allogeneic GM-CSF transfected pancreatic tumor cell lines. Overall survival is defined as time from surgery until death, regardless of cause.	Participants were followed for the duration of the study, an average of 2 years
Disease-free Survival	Disease-free Survival in Patients Treated With Adjuvant Chemoradiotherapy in Sequence With the Irradiated Allogeneic GM-CSF Transfected Pancreatic Tumor Cell Lines. DFS is defined as time from surgery until clinical evidence of disease (eg, CT scan) or death due to any cause.	Participants were followed for the duration of the study, an average of 2 years

Secondary Outcome Measures	Measure Description	Time Frame
To Further Identify and Characterize Toxicities Associated With Intradermal Injections of the Vaccine That Were Initially Reported in the Phase 1 Trial.		4 years
Estimate the Association of Specific in Vivo Parameters of Immune Response With Clinical Responses in Patients Treated With Combination Chemoradiotherapy Together With the Irradiated Allogeneic GM-CSF Transfected Pancreatic Tumor Cell Lines.	The specific immune parameters include: post-vaccination delayed type hypersensitivity reactions to autologous tumor and the degree of local eosinophil, macrophage, and T cell infiltration at the vaccine site, and mesothelin-specific T cell responses.	Continuous

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

18 and over

ECOG 0-1

Not specified

Absolute neutrophil count >/= 1,500/mm^3
Platelet count >/= 100,000/mm^3
Hemoglobin >/= 10 g/dL

Bilirubin
AST/ALT
Alkaline phosphatase
Renal

Creatinine
Pulmonary

No asthma or chronic obstructive pulmonary disease requiring systemic corticosteroids

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

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

More than 1 month since prior biologic therapy
No other concurrent biologic therapy, immunotherapy, or gene therapy for pancreatic cancer

More than 1 month since prior chemotherapy
No other concurrent chemotherapy for pancreatic cancer

More than 28 days since prior systemic steroids
No concurrent systemic corticosteroids

More than 1 month since prior radiotherapy
No other concurrent radiotherapy for pancreatic cancer

See Disease Characteristics
Recovered from prior surgery

More than 1 month since prior participation in an investigational new drug trial
No other concurrent investigational therapy for pancreatic cancer

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

National Cancer Institute (NCI)

Investigators

PRINCIPAL_INVESTIGATOR: Daniel A. Laheru, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Lutz E, Yeo CJ, Lillemoe KD, Biedrzycki B, Kobrin B, Herman J, Sugar E, Piantadosi S, Cameron JL, Solt S, Onners B, Tartakovsky I, Choi M, Sharma R, Illei PB, Hruban RH, Abrams RA, Le D, Jaffee E, Laheru D. A lethally irradiated allogeneic granulocyte-macrophage colony stimulating factor-secreting tumor vaccine for pancreatic adenocarcinoma. A Phase II trial of safety, efficacy, and immune activation. Ann Surg. 2011 Feb;253(2):328-35. doi: 10.1097/SLA.0b013e3181fd271c.

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