Avastin, Fluorouracil, Doxorubicin and Streptozocin in Locally Advanced and Metastatic Pancreatic Endocrine Tumors

• Status: Terminated
• Trial end date: 2008-03-01
• Target enrollment: 0
• Participant gender: All

Summary

Open label, single-arm phase II study of avastin combined with fluorouracil, doxorubicin and streptozocin administered in 28-day cycles. Treatment will continue until progression of disease, or until withdrawal due to toxicity, or up to a maximum of 12 cycles (48 weeks). In order to reduce the risk of cardiac toxicity, doxorubicin will be administered for a maximum of 8 cycles. If disease has not progressed after 12 cycles of treatment, avastin monotherapy will continue until disease progression or withdrawal due to toxicity.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Collaborator: Genentech, Inc.
• Treatments: BB 1101; Bevacizumab; Dexamethasone; Dexamethasone 21-phosphate; Dexamethasone acetate; Doxorubicin; Fluorouracil; Liposomal doxorubicin; Ondansetron; Streptozocin

Criteria

Inclusion Criteria:

• Patients must have locally advanced (unresectable) or metastatic, well or moderately differentiated pancreatic endocrine tumors.

• Measurable disease on CT scan or MRI.

• Age ≥ 18 years and ≤ 80 years.

• Use of effective means of contraception (men and women) in subjects of child-bearing potential

• Adequate renal function (serum creatinine ≤1.5, urine protein:creatinine ratio <1.0 or urine dipstick for proteinuria < 2+ (patients discovered to have ≥ 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate ≤ 1 g of protein in 24 hours to be eligible).

• Adequate hepatic function (bilirubin ≤2.0, AST and ALT ≤ 3x ULN.

• Adequate hematologic function (WBC ≥ 3,000, ANC ≥ 1500, platelets ≥ 100,000)

Exclusion Criteria:

• Prior therapy with fluorouracil, doxorubicin, streptozocin or avastin

• Ejection fraction on MUGA <50%

• ECOG performance status > 2

• Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored avastin cancer study

• Inadequately controlled hypertension (defined as systolic blood pressure >150 and/or diastolic blood pressure > 100 mmHg on antihypertensive medications)

• Any prior history of hypertensive crisis or hypertensive encephalopathy

• Unstable angina

• New York Heart Association (NYHA) Grade II or greater congestive heart failure

• History of myocardial infarction or unstable angina within 6 months prior to study enrollment

• History of stroke or transient ischemic attack within 6 months prior to study enrollment

• Significant vascular disease (e.g., aortic aneurysm, aortic dissection)

• Symptomatic peripheral vascular disease

• Evidence of bleeding diathesis or coagulopathy

• Presence of central nervous system or brain metastases

• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, anticipation of need for major surgical procedure during the course of the study

• Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment

• Pregnant (positive pregnancy test) or lactating. Use of effective means of contraception (men and women) in subjects of child-bearing potential

• Proteinuria at screening as demonstrated by either

• Urine protein: creatinine (UPC) ratio ≥ 1.0 at screening OR

• Urine dipstick for proteinuria ≥ 2+ (patients discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate ≤ 1g of protein in 24 hours to be eligible).

• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0

• Evidence of duodenal invasion on CT scan, MRI, or endoscopy

• Known hypersensitivity to any component of avastin

• Serious, non-healing wound, ulcer, or bone fracture

• Inability to comply with study and/or follow-up procedures