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

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ClinicalTrials.gov Identifier: NCT00084383
Recruitment Status : Completed
First Posted : June 11, 2004
Results First Posted : July 15, 2013
Last Update Posted : July 22, 2013
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Tracking Information
First Submitted Date  ICMJE June 10, 2004
First Posted Date  ICMJE June 11, 2004
Results First Submitted Date  ICMJE March 1, 2013
Results First Posted Date  ICMJE July 15, 2013
Last Update Posted Date July 22, 2013
Study Start Date  ICMJE January 2002
Actual Primary Completion Date December 2005   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 10, 2013)
  • Overall Survival [ Time Frame: Participants were followed for the duration of the study, an average of 2 years ]
    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.
  • Disease-free Survival [ Time Frame: Participants were followed for the duration of the study, an average of 2 years ]
    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.
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00084383 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 8, 2011)
  • To Further Identify and Characterize Toxicities Associated With Intradermal Injections of the Vaccine That Were Initially Reported in the Phase 1 Trial. [ Time Frame: 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. [ Time Frame: Continuous ]
    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.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Vaccine Therapy Combined With Adjuvant Chemoradiotherapy in Treating Patients With Resected Stage I or Stage II Adenocarcinoma (Cancer) of the Pancreas
Official Title  ICMJE 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
Brief Summary

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.

Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Pancreatic Cancer
Intervention  ICMJE 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 therapy is standard of care and not part of the protocol) eligible patients will receive three additional vaccinations at one month intervals. Patients who continue to remain disease-free will receive a fifth "booster" vaccination, six months following the fourth vaccination.
Study Arms  ICMJE 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 protocol) eligible patients will receive three additional vaccinations at one month intervals. Patients who continue to remain disease-free will receive a fifth "booster" vaccination, six months following the fourth vaccination
Intervention: Biological: GVAX pancreatic cancer vaccine
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 8, 2011)
60
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE July 2006
Actual Primary Completion Date December 2005   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 </= 2 mg/dL
  • AST/ALT </= 2 times upper limit of normal (ULN)
  • Alkaline phosphatase </= 5 times ULN

Renal

  • Creatinine </= 2 mg/dL

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00084383
Other Study ID Numbers  ICMJE J9988
R01CA088058 ( U.S. NIH Grant/Contract )
P30CA006973 ( U.S. NIH Grant/Contract )
JHOC-J9988
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study Sponsor  ICMJE Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Daniel A. Laheru, MD Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
PRS Account Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Verification Date July 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP