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

Phase 2

Terminated

Conditions: Pancreatic Cancer

Interventions: Drug: Avastin
Drug: Fluorouracil
Drug: Doxorubicin
Drug: Streptozocin
Drug: Dexamethasone
Drug: Ondansetron

Registration Number: NCT00609765

Lead Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Brief 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.

Detailed Description: Patients will need to come for 24 study visits in all. Most study visits will take about 2 hours. At some of these study visits, the doctor

* Will do a physical exam

* Will take blood for routine lab tests

* Will do a urinalysis

* Will administer study medication Some study visits may be longer because patient will have a CT scan or an MRI.

At patient's last visit, they will have a CT scan or MRI.

After treatment starts, patient will:

* Have their blood pressure monitored with every dose of Avastin® (about every 2 weeks).

* Have a history and physical with every chemotherapy cycle (about every 4 weeks).

* Have their blood taken for routine blood tests with every chemotherapy cycle (about every 4 weeks).

* Have a CT scan or MRI during every other cycle (about every 8 weeks).

* Have a MUGA scan during every 4 cycles (about 16 weeks).

* Have blood taken for tumor markers during every cycle only if their markers were high at baseline.

* Patients will receive study medication to treat their cancer:

* Fluorouracil on days 1 through 5 of each cycle through cycle 12

* Doxorubicin on day 1 of each cycle through cycle 8

* Streptozocin on days 1 through 5 of each cycle through cycle 12

* Avastin® on days 1 and 15 of each cycle through cycle 12

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 1

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Protocol Specified Chemotherapy	Avastin	Protocol Specified Chemotherapy Every 28 Days: Avastin, Fluorouracil, Doxorubicin, Streptozocin. Premedications: Dexamethasone, Ondansetron
Protocol Specified Chemotherapy	Doxorubicin	Protocol Specified Chemotherapy Every 28 Days: Avastin, Fluorouracil, Doxorubicin, Streptozocin. Premedications: Dexamethasone, Ondansetron
Protocol Specified Chemotherapy	Fluorouracil	Protocol Specified Chemotherapy Every 28 Days: Avastin, Fluorouracil, Doxorubicin, Streptozocin. Premedications: Dexamethasone, Ondansetron
Protocol Specified Chemotherapy	Streptozocin	Protocol Specified Chemotherapy Every 28 Days: Avastin, Fluorouracil, Doxorubicin, Streptozocin. Premedications: Dexamethasone, Ondansetron
Protocol Specified Chemotherapy	Dexamethasone	Protocol Specified Chemotherapy Every 28 Days: Avastin, Fluorouracil, Doxorubicin, Streptozocin. Premedications: Dexamethasone, Ondansetron
Protocol Specified Chemotherapy	Ondansetron	Protocol Specified Chemotherapy Every 28 Days: Avastin, Fluorouracil, Doxorubicin, Streptozocin. Premedications: Dexamethasone, Ondansetron

Primary Outcome Measures

Name	Time	Method
Number of Participants With Progression Free Survival (PFS) at 12 Months	12 months	We planned to calculate the One Year Progression Free Survival rate. The event for PFS analyses was the first occurrence of disease progression or death and patients who did not progress or died would be censored at the date of last tumor evaluation (e.g. one-year).

Secondary Outcome Measures

Name	Time	Method
The Number of Participants With Radiographic Response	2 years	Objective Radiographic Response Rate (ORR). We planned to calculate the sum of complete response (CR) and partial response (PR) in target lesions.