Gemcitabine, Cisplatin, and Bevacizumab 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 cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving gemcitabine and cisplatin together with bevacizumab may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving gemcitabine and cisplatin together with bevacizumab works in treating patients with metastatic pancreatic cancer.

Detailed Description
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OBJECTIVES: Primary Determine time to disease progression in patients with previously untreated metastatic adenocarcinoma of the pancreas treated with gemcitabine, cisplatin, and bevacizumab. Determine the safety and toxicity of this regimen in these patients. Secondary Determine the objective response rate in patients treated with this regimen. Determine the efficacy of this regimen, in terms of the proportion of patients with ≥ a 50% decline in the CA19-9 biomarker, in these patients. Determine the median survival of patients treated with this regimen. Correlate serum markers of angiogenesis and circulating tumor micrometastases with clinical outcome of patients treated with this regimen. OUTLINE: This is an open-label, non-randomized study. Patients receive gemcitabine IV over 100 minutes, cisplatin IV over 30-60 minutes, and bevacizumab* IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients may receive additional study treatment at the discretion of the investigator. NOTE: *Patients may continue to receive other components of therapy if bevacizumab is discontinued due to toxicity. After completion of study treatment, patients are followed at 28 days and then monthly thereafter. PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study within 12-18 months.

Official Title
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A Study of Fixed-Dose Rate Gemcitabine, Cisplatin, and Bevacizumab in Previously Untreated Patients With Metastatic Pancreatic Cancer

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Biological: bevacizumab
* Drug: cisplatin
* Drug: gemcitabine hydrochloride


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed adenocarcinoma of the pancreas Must have documented extrapancreatic metastases Radiographically measurable disease is not required Previously untreated disease No CNS or brain metastases PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-2 Life expectancy Not specified Hematopoietic Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 9 g/dL (transfusion or epoetin alfa [Epogen®] support allowed) No evidence of bleeding diathesis or coagulopathy Hepatic INR ≤ 1.5 (except for patients receiving full-dose warfarin) Bilirubin ≤ 2.0 mg/dL AST or ALT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastases are present) Renal Creatinine ≤ 2.0 mg/dL Urine protein:creatinine ratio ≤ 1 Cardiovascular No New York Heart Association class II-IV congestive heart failure No myocardial infarction or stroke within the past 6 months No uncontrolled hypertension (i.e., blood pressure > 160/110 mm Hg despite antihypertensive therapy) No unstable angina No unstable symptomatic arrhythmia requiring medication Patients with chronic atrial arrhythmia (i.e., atrial fibrillation or paroxysmal supraventricular tachycardia) are eligible No peripheral vascular disease ≥ grade 2 Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 6 months after completion of study treatment No significant traumatic injury within the past 28 days No serious non-healing wound, ulcer, or bone fracture No other malignancy within the past 5 years except curatively treated nonmelanoma skin cancer or carcinoma in situ of the cervix No other serious systemic disease No history of any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that would preclude study treatment PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy Not specified Endocrine therapy Not specified Radiotherapy Not specified Surgery More than 28 days since prior major surgery, or open biopsy More than 7 days since prior fine needle aspirations or core biopsies No concurrent major surgery Other No prior therapy, including systemic or investigational therapy, for locally advanced or metastatic pancreatic cancer Treatment given in the adjuvant setting (e.g., radiotherapy and/or chemotherapy, given either concurrently or systemically) is not considered prior therapy provided progressive disease occurred > 6 months after completion of prior treatment Concurrent continuation of therapeutic doses of warfarin or low-molecular weight heparin allowed for pulmonary embolism, deep vein thrombosis, atrial fibrillation, or other clinical indications provided patients has been on a stable dose for ≥ 28 days with no further clotting or bleeding complications

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: bevacizumab|nan|
|Drug: cisplatin|nan|
|Drug: gemcitabine hydrochloride|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression |  |  | 
| Duration of response |  |  | 
| Overall survival |  |  | 
| Toxicity as measured by NCI CTC version 2.0 |  |  | 
| Micrometastases for predicting time to progression and overall survival |  |  | 

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