Gemcitabine and Capecitabine With or Without Vaccine Therapy in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as gemcitabine and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vaccines made from peptides may help the body build an effective immune response to kill tumor cells. Giving more than one drug (combination chemotherapy) together with vaccine therapy may kill more tumor cells. It is not yet known whether chemotherapy is more effective with or without vaccine therapy in treating pancreatic cancer. PURPOSE: This randomized phase III trial is studying gemcitabine, capecitabine, and vaccine therapy to see how well they work compared with gemcitabine and capecitabine alone in treating patients with locally advanced or metastatic pancreatic cancer.

Detailed Description
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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.

Official Title
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A Prospective, Phase III, Controlled, Multicentre, Randomised Clinical Trial Comparing Combination Gemcitabine and Capecitabine Therapy With Concurrent and Sequential Chemoimmunotherapy Using a Telomerase Vaccine in Locally Advanced and Metastatic Pancreatic Cancer [TELOVAC]

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Biological: sargramostim
* Biological: telomerase peptide vaccine GV1001
* Drug: capecitabine
* Drug: gemcitabine hydrochloride


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: sargramostim|nan|
|Biological: telomerase peptide vaccine GV1001|nan|
|Drug: capecitabine|nan|
|Drug: gemcitabine hydrochloride|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival at 1 year |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression |  |  | 
| 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 |  |  | 
| Clinical benefit response |  |  | 
| Objective response rate as assessed by RECIST criteria |  |  | 
| Toxicity as assessed by NCI CTCAE version 3 |  |  | 
| Survival and response as assessed by delayed-type hypersensitivity |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage III pancreatic cancer, stage IV pancreatic cancer, duct cell adenocarcinoma of the pancreas, recurrent pancreatic cancer