A Phase I/II Study of Fixed-Dose Rate Gemcitabine and Bevacizumab for Postoperative Adjuvant Treatment of Patients With Resected Pancreatic Cancer
A Phase I/II Study of Fixed-Dose Rate Gemcitabine and Bevacizumab for Postoperative Adjuvant Treatment of Patients With Resected Pancreatic Cancer
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. 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 pancreatic cancer by blocking blood flow to the tumor. Giving gemcitabine and bevacizumab after surgery may kill any tumor cells that remain after surgery.
PURPOSE: This phase I/II trial is studying the side effects of gemcitabine and bevacizumab and to see how well they work in treating patients with pancreatic cancer that has been completely removed by surgery.
OBJECTIVES:
Primary
Secondary
OUTLINE: This is an open-label, non-randomized study.
Patients receive gemcitabine hydrochloride IV over 100 minutes followed by bevacizumab* IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease recurrence or unacceptable toxicity.
NOTE: *The first dose of bevacizumab is not administered until after 6 weeks have passed since surgery.
After completion of study therapy, patients are followed periodically for 18 months.
PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.
DISEASE CHARACTERISTICS:
Histologically or cytologically confirmed adenocarcinoma of the pancreas
Completely resected disease
Underwent 1 of the following procedures 3-8 weeks ago:
No grossly positive surgical margins
Nonmeasurable disease
No known CNS disease
PATIENT CHARACTERISTICS:
ECOG performance status 0-1
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 6 months after completion of study therapy
CA 19-9 ≤ 2.5 times upper limit of normal (ULN)
Absolute neutrophil count ≥ 1,500/mm³
Hemoglobin ≥ 9 g/dL (transfusion or epoetin alfa allowed)
Platelet count ≥ 100,000/mm³
INR ≤ 1.5 (except in patients receiving full-dose warfarin)
Bilirubin ≤ 2.0 mg/dL
AST and ALT ≤ 2.5 times ULN
Creatinine ≤ 2.0 mg/dL
No clinically significant impairment of renal function
No postoperative complications, including any of the following:
No abdominal fistula, gastrointestinal perforation, or intra-abdominal abcess within the past 6 months
No history of major psychiatric disorder or other chronic medical illness that, in the opinion of the treating physician, contraindicates use of the study drugs or renders the patient at high risk of treatment-related complications
No other cancer within the past 5 years except basal cell or squamous cell skin cancer
No history of serious systemic disease, including any of the following:
Myocardial infarction or unstable angina within the past 12 months
New York Heart Association class II-IV congestive heart failure
Unstable symptomatic arrhythmia requiring medication
No history of stroke or transient ischemic attack
No symptomatic peripheral vascular disease
No significant vascular disease (e.g., aortic aneurysm, aortic dissection)
No inadequately controlled hypertension (i.e., blood pressure > 150/100 mm Hg on antihypertensive medication)
No prior hypertensive crisis or hypertensive encephalopathy
No proteinuria (defined as urine protein:creatinine ratio ≥ 1.0 OR proteinuria ≥ 2+ by dipstick urinalysis OR protein > 1 g by 24-hour urine collection)
No serious, nonhealing wound or ulcer
No evidence of bleeding diathesis or coagulopathy
No significant traumatic injury within the past 28 days
PRIOR CONCURRENT THERAPY:
See Disease Characteristics
No prior chemotherapy or radiotherapy for pancreatic cancer
No prior systemic or investigational therapy for pancreatic cancer
No major surgical procedure (except for resection of pancreatic cancer) or open biopsy within the past 28 days
No fine-needle aspiration or core biopsy within the past 7 days
No anticipated need for a major surgical procedure during study treatment
No concurrent newly prescribed nonsteroidal anti-inflammatory drugs (NSAIDs)