Chemotherapy With or Without Dalteparin in Treating Patients With 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. Anticoagulants, such as dalteparin, may help prevent blood clots from forming in patients being treated with chemotherapy. It is not yet known whether gemcitabine is more effective when given alone or together with dalteparin and/or capecitabine in treating patients with pancreatic cancer. PURPOSE: This randomized phase III trial is studying whether dalteparin prevents blood clots in patients with pancreatic cancer receiving treatment with different combinations of gemcitabine and capecitabine.

Detailed Description
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OBJECTIVES: Primary To demonstrate that preventive anticoagulation with dalteparin reduces the number of thromboembolic events. To determine the number of thromboembolic events occurring with preventive anticoagulation. Secondary To determine survival without thrombotic event. To determine progression-free and overall survival. To determine time to response of tumor. To assess tolerance of these regimens. OUTLINE: This is a multicenter study. Patients are stratified according to participating center and WHO performance status (0-1 vs 2). Patients are randomized to 1 of 4 treatment arms. Arm A: Patients receive chemotherapy at investigator's discretion Arm B Patients receive chemotherapy at investigator's discretion and dalteparin In all arms, treatment repeats in the absence of disease progression or unacceptable toxicity. Blood and plasma samples are obtained at baseline and periodically during study. Blood is examined for biomarkers, resistance to activated protein C, and mutations (Leiden V factor, mutation G20210A, and the factor II gene). Thrombin generation and factors VIIa and VIII are assessed in plasma. After completion of study therapy, patients are followed periodically.

Official Title
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Chemotherapy With or Without Preventive Anticoagulation for Metastatic Cancer of the Pancreas

Conditions
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Chemotherapeutic Agent Toxicity, Pancreatic Cancer, Thromboembolism

Intervention / Treatment
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* Drug: daltéparine
* Drug: Chemotherapy at the investigator's discretion


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the pancreas Metastatic disease Not amenable to treatment No localized or locally advanced disease Measurable disease (metastatic or primary tumor) defined as ≥ 2 cm by CT scan or ≥ 1 cm by spiral CT scan or MRI No progressive thrombo-embolic disease No adenocarcinoma of the biliary tract or ampulla of Vater No known CNS metastases PATIENT CHARACTERISTICS: WHO performance status 0-2 Life expectancy > 12 weeks ANC ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 9 g/dL Alkaline phosphatase < 5 times normal Bilirubin < 1.5 times normal Creatinine < 1.5 times normal Creatinine clearance < 30 mL/min Pain controlled or stabilized via analgesic therapy Affiliation with social security system Not pregnant or nursing No controlled or uncontrolled jaundice No contraindication to study drugs No cardiovascular accident (myocardial infarction, cerebral vascular accident) within the past 6 months No serious cardiac and/or respiratory disease No other cancer in the past 5 years except the following cancers, provided they have been completely resected: Skin cancer Localized melanoma Carcinoma in situ of the cervix No history of thrombophilia No history of heparin-induced thrombocytopenia No uncontrolled or persistent hypercalcemia No psychological, familial, social, and/or geographical condition that precludes participation in the study PRIOR CONCURRENT THERAPY: No prior hematologic therapy for metastatic disease No prior abdominal radiotherapy No concurrent corticosteroids as anti-emetic therapy No other concurrent anticoagulation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: chemotherapy<br>chemotherapy at investigator's discretion | Drug: Chemotherapy at the investigator's discretion<br> <br> |
| Experimental: dalteparin<br>dalteparin: 5000 UI sub-cutaneous injection, from Day 1 to Day 28. | Drug: daltéparine<br> <br> Drug: Chemotherapy at the investigator's discretion<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Thromboembolic events | number of thromboembolic events during anticoagulation treatment | during study treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  | at 6 months | 
| Overall survival |  | at one year | 
| Tolerance of regimens |  | each cycle | 

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