• Survival at 1 year [ Designated as safety issue: No ]
  

• Time to progression [ Designated as safety issue: No ]
  
• Quality of life as assessed by the European Organization for Research and Treatment of Cancer (EORTC)-Quality of Life (QLQ) C30 questionnaire and the European Study group for Pancreatic Cancer-QLQ questionnaire [ Designated as safety issue: No ]
  
• Clinical benefit response [ Designated as safety issue: No ]
  
• Objective response rate as assessed by RECIST criteria [ Designated as safety issue: No ]
  
• Toxicity as assessed by NCI CTCAE version 3 [ Designated as safety issue: Yes ]
  
• Survival and response as assessed by delayed-type hypersensitivity [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Determine the efficacy of telomerase peptide vaccine GV1001 when administered concurrently or sequentially with gemcitabine hydrochloride and capecitabine, in terms of survival, in patients with locally advanced or metastatic pancreatic cancer.

Secondary

• Determine the safety of this regimen in these patients.
• Assess the immunogenicity of this regimen in these patients.
• Determine the time to progression in patients treated with this regimen.
• Determine the quality of life of patients treated with this regimen.
• Determine the clinical benefit response in patients treated with this regimen.
• Determine the objective response rate in patients treated with this regimen.
• Determine the toxicity of this regimen in these patients.
• Determine the survival and response by delayed-type hypersensitivity in patients treated with this regimen.

OUTLINE: This is a prospective, controlled, randomized, open-label, multicenter study. Patients are stratified according to stage of disease (locally advanced vs metastatic) and ECOG performance status (0 vs 1 vs 2). Patients are randomized to 1 of 3 treatment arms.

• Arm I: Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 and oral capecitabine twice daily on days 1-21. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive gemcitabine hydrochloride and capecitabine as in arm I. Treatment repeats every 4 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients then receive sargramostim (GM-CSF) intradermally (ID) and telomerase peptide vaccine GV1001 ID on days 1, 3, and 5 in week 9, once a week in weeks 10-12 and 14, and then once a month in the absence of disease progression or unacceptable toxicity. Patients who develop disease progression while on vaccine therapy, discontinue vaccine therapy and then restart treatment with gemcitabine hydrochloride and capecitabine. Patients receive gemcitabine hydrochloride and capecitabine as above and continue treatment in the absence of further disease progression or unacceptable toxicity.
• Arm III: Patients receive gemcitabine hydrochloride and capecitabine as in arm I. Patients also receive GM-CSF ID and telomerase peptide vaccine GV1001 ID on days 1, 3, and 5 in week 1, once weekly in weeks 2, 3, 4 and 6, and then once a month in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline and at 8 weeks and then every 12 weeks during study treatment.

After completion of study treatment, patients are followed every 3 months.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 1,110 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed pancreatic ductal adenocarcinoma or undifferentiated carcinoma of the pancreas

  • Locally advanced or metastatic disease precluding curative surgical resection
• Unidimensionally measurable disease by CT scan
• No intracerebral metastases or meningeal carcinomatosis

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy > 3 months
• WBC > 3,000/mm³
• Absolute neutrophil count > 1,500/mm³
• Platelet count > 100,000/mm³
• Bilirubin < 2.0 mg/dL
• Creatinine clearance > 50 mL/min
• No medical or psychiatric condition that would preclude giving informed consent
• No clinically significant serious disease or organ system disease not currently controlled on present therapy
• No uncontrolled angina pectoris
• Not pregnant or nursing
• Fertile patients must use a condom and ≥ 1 other form of contraception during and for 1 year after completion of study treatment
• No other malignancies or invasive cancers within the past 5 years except for adequately treated basal cell carcinoma of the skin or carcinoma in situ of the cervix
• No known malabsorption syndrome
• No known hypersensitivity to any of the investigational agents
• No dihydropyrimidine dehydrogenase deficiency

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy
• No radiotherapy within the past 4 weeks

• No concurrent medications that could affect immunocompetence (e.g., chronic treatment with long-term steroids or other immunosuppressants for unrelated condition)

  • Concurrent short-term steroids for palliation of cancer-related symptoms allowed
• No other concurrent investigational drugs or cytotoxic agents

• No other concurrent immunotherapy (e.g., immunosuppressants or chronic use of systemic corticosteroids) or chemotherapy for another tumor in patients receiving telomerase peptide vaccine GV1001

  • Concurrent low-dose corticosteroids may be allowed