Gemcitabine, Capecitabine, and Bevacizumab in Treating Patients With Metastatic or Unresectable 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. Bevacizumab may stop the growth of tumor cells by stopping blood flow to the tumor. Giving gemcitabine and capecitabine together with bevacizumab may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving gemcitabine and capecitabine together with bevacizumab works in treating patients with metastatic or unresectable pancreatic cancer.

Detailed Description
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OBJECTIVES: Primary Determine progression-free survival of patients with metastatic or unresectable adenocarcinoma of the pancreas treated with gemcitabine, capecitabine, and bevacizumab. Secondary Determine clinical response in patients treated with this regimen. Determine toxicity of this regimen in these patients. Determine quality of life of patients treated with this regimen. OUTLINE: This is an open-label, multicenter study. Patients receive bevacizumab IV over 30-90 minutes on day 1, oral capecitabine twice daily on days 1-14, and gemcitabine IV over 30 minutes on days 1 and 8. Courses repeat every 21 days for up to 12 months in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline then weekly for 3 weeks. Patients are followed every 2-4 months for 1 year and then every 6 months for at least 5 years. PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study within 8.8-17.5 months.

Official Title
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Multicenter, Open Label, Phase II Clinical Study of Gemcitabine, Capecitabine and Avastin in Pancreatic Cancer

Conditions
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Pancreatic Cancer

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


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the pancreas meeting 1 of the following criteria: Newly diagnosed or previously treated metastatic disease Unresectable disease No CNS or brain metastases PATIENT CHARACTERISTICS: Age Over 18 Performance status ECOG 0-1 Life expectancy More than 3 months Hematopoietic Absolute neutrophil count > 1,500/mm^3 WBC > 3,000/mm^3 Platelet count > 100,000/mm^3 Hemoglobin ≥ 9 g/dL (transfusion or epoetin alfa allowed) No evidence of bleeding diathesis or coagulopathy Hepatic Bilirubin < 2 mg/dL AST or ALT < 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastases are present) INR < 1.5 (except for patients receiving full-dose warfarin) Renal Creatinine < 1.5 mg/dL No proteinuria OR Urine protein < 500 mg by 24-hour urine collection No clinically significant impairment of renal function Cardiovascular No uncontrolled hypertension (blood pressure > 160/110 mm Hg on medication) No New York Heart Association class II-IV congestive heart failure No unstable symptomatic arrhythmia requiring medication Chronic atrial arrhythmia (i.e., atrial fibrillation or paroxysmal supraventricular tachycardia) allowed No clinically significant grade II-IV peripheral vascular disease No arterial thromboembolic event within the past 6 months, including any of the following: Transient ischemic attack Cerebrovascular accident Unstable angina Myocardial infarction Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No other serious systemic disease No significant traumatic injury within the past 28 days No serious non-healing wound, ulcer, or bone fracture No history of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that would preclude study participation 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 More than 4 weeks since prior and no concurrent participation in any other experimental drug study More than 12 months since prior adjuvant therapy No prior systemic therapy for metastatic disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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|30-90 minutes on day 1, every 21 days up to 12 months.|
|Drug: capecitabine|twice daily on days 1-14. Courses repeat every 21 days for up to 12 months in the absence of disease progression or unacceptable toxicity.|
|Drug: gemcitabine hydrochloride|IV over 30 minutes on days 1 and 8. Courses repeat every 21 days for up to 12 months in the absence of disease progression or unacceptable toxicity.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | Progressive Disease is defined using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee [JNCI 92(3):205-216, 2000], as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions, or appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. | every 2-4 months for 1 year and then every 6 months for 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Grades 3-5 Treatment Related Toxicities | Grade 3, 4 or 5 toxicity rate | Subjects were evaluated for adverse events at each study visit for the duration of their participation in the study, up to 5 years | 
| Percentage of Participants With Improved Quality of Life | Quality of Life was assessed using EORTC QLQ-PAN26. All measures range in score from 1 to 4 as lower scores indicate better outcomes. The improved Quality of Life is defined as a greater than 5% decrease in 2 consecutive scores compared with the baseline score. | assessed at baseline then weekly for 3 weeks | 
| Clinical Response | Response was evaluated using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee [JNCI 92(3):205-216, 2000]. Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter; Overall Response (OR) = CR + PR. | Pre-treatment and every 6 weeks from treatment. | 
| Overall Survival |  | every 2-4 months for 1 year and then every 6 months for 5 years | 

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