Gemcitabine With or Without Dalteparin 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, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Anticoagulants, such as dalteparin, may help prevent blood clots from forming in patients being treated with gemcitabine for pancreatic cancer. PURPOSE: This randomized phase II trial is studying how well gemcitabine works with or without dalteparin in treating patients with locally advanced or metastatic pancreatic cancer.

Detailed Description
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OBJECTIVES: Primary Compare the incidence of venous thromboembolism in patients with locally advanced or metastatic pancreatic cancer treated with gemcitabine hydrochloride and dalteparin versus gemcitabine hydrochloride alone. Secondary Compare the survival benefit, in terms of increased (from 70% to 85%) survival at 12 weeks, of patients treated with these regimens. Compare the toxicity of these regimens. Compare the overall survival of patients treated with these regimens. Compare the time to disease progression in patients treated with these regimens. Determine the effect of gemcitabine hydrochloride and dalteparin on serological markers of thromboangiogenesis. OUTLINE: This is a multicenter, randomized study. Patients are stratified according to disease progression (locally advanced vs metastatic) and Karnofsky performance status (≥ 80% vs < 80%). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive gemcitabine hydrochloride IV over 30 minutes once weekly in weeks 1-7 and 9-11. Arm II: Patients receive low molecular weight dalteparin subcutaneously once daily in weeks 1-12. Patients also receive gemcitabine hydrochloride as in arm I. Blood samples are acquired at baseline for analysis of circulating tissue factor and vascular endothelial growth factor. After completion of study treatment, patients are followed periodically. PROJECTED ACCRUAL: A total of 120 patients will be accrued for this study.

Official Title
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A Phase II Randomized Study of Chemo-Anticoagulation (Gemcitabine-Dalteparin) Versus Chemotherapy Alone (Gemcitabine) for Locally Advanced and Metastatic Pancreatic Adenocarcinoma [FRAGEM]

Conditions
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Pancreatic Cancer, Thromboembolism

Intervention / Treatment
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* Drug: dalteparin
* Drug: gemcitabine hydrochloride
* Other: diagnostic laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed metastatic or locally advanced adenocarcinoma of the pancreas Patients with clinical 'high probability' of pancreatic cancer and biopsy suggestive but not diagnostic of pancreatic cancer may be eligible based on review by the principal investigator Measurable or evaluable disease No clinical evidence of active venous thromboembolism PATIENT CHARACTERISTICS: Karnofsky performance status (PS) 60-100% OR WHO PS 0-2 Life expectancy > 12 weeks Absolute neutrophil count > 2,000/mm³ WBC > 3,000/mm³ Platelet count > 100,000/mm³ Creatinine clearance > 50 mL/min INR ≤ 1.5 times upper limit of normal (ULN) Bilirubin < 1.5 times ULN (stent allowed) Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No cerebrovascular accident within the past 6 months No obvious contraindication to anticoagulation, including the following: Bleeding diathesis Active peptic ulcer Ulcerating cancer into duodenum No history of other advanced malignancy No gross hematuria No melaena or gross evidence of gastrointestinal bleeding (other than piles) No requirement for a central line No other significant medial or psychiatric illness that, in the opinion of the investigator, would preclude study participation PRIOR CONCURRENT THERAPY: No prior gemcitabine hydrochloride-containing treatment No other concurrent cytotoxic chemotherapy, immunotherapy, hormonal therapy (excluding contraceptives and replacement steroids), or experimental medications No other concurrent specific anticancer therapy as a result of disease progression No concurrent caval filter device No other concurrent anticoagulants for venous thromboembolism or other reasons (e.g., atrial fibrillation) No concurrent acetylsalicylic acid (> 75 mg) as an antiplatelet drug for a preexisting cardiovascular condition No concurrent clopidogrel bisulfate

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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: dalteparin|nan|
|Drug: gemcitabine hydrochloride|nan|
|Other: diagnostic laboratory biomarker analysis|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of venous thromboembolism reduction |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Early survival benefit |  |  | 
| Toxicity |  |  | 
| Overall survival |  |  | 
| Time to disease progression |  |  | 
| Effect of drug combination on serological markers of thromboangiogenesis |  |  | 

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