Avastin, Fluorouracil, Doxorubicin and Streptozocin in Locally Advanced and Metastatic Pancreatic Endocrine Tumors
Condition: Pancreatic Cancer
MeSH terms: Endocrine Gland Neoplasms
Intervention: Avastin; Fluorouracil; Doxorubicin; Streptozocin; Dexamethasone; Ondansetron
Intervention description: Every 28 Days: Avastin 5mg/kg iv days 1 and 15; Every 28 Days: Fluorouracil 400mg/m^2 iv bolus daily days 1-5; Every 28 Days: Doxorubicin 40mg/m^2 iv bolus day 1; Every 28 Days: Streptozocin 400mg/m2 iv bolus daily days 1-5; Premedication: Dexamethasone 20mg intravenously days 1-5; Premedication: Ondansetron 16mg intravenously days 1-5
Intervention MeSH terms: Dexamethasone; Bevacizumab; Doxorubicin; Fluorouracil; Streptozocin; Ondansetron
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: advanced; unresectable; metastatic; endocrine; tumors

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.
    

Eligibility 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