Avastin, Fluorouracil, Doxorubicin And Streptozocin In Locally Advanced And Metastatic Pancreatic Endocrine Tumors

Study Overview

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

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.

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

Pancreatic Cancer

DRUG: Avastin
DRUG: Fluorouracil
DRUG: Doxorubicin
DRUG: Streptozocin
DRUG: Dexamethasone
DRUG: Ondansetron

MCC-14961
AVF3915s (OTHER Identifier) (OTHER: Genentech)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2008-01-24	Results First Submitted 2011-02-21	Last Update Submitted that met QC Criteria 2017-02-20
First Submitted that Met QC Criteria 2008-02-06	Results First Submitted that Met QC Criteria 2011-02-21	Last Update Posted (ACTUAL) 2017-03-23
First Posted (ACTUAL) 2008-02-07	Results First Posted 2011-03-22	Last Verified 2011-03

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Protocol Specified Chemotherapy Protocol Specified Chemotherapy Every 28 Days: Avastin, Fluorouracil, Doxorubicin, Streptozocin. Premedications: Dexamethasone, Ondansetron	DRUG: Avastin Every 28 Days: Avastin 5mg/kg iv days 1 and 15 DRUG: Fluorouracil Every 28 Days: Fluorouracil 400mg/m^2 iv bolus daily days 1-5 DRUG: Doxorubicin Every 28 Days: Doxorubicin 40mg/m^2 iv bolus day 1 DRUG: Streptozocin Every 28 Days: Streptozocin 400mg/m2 iv bolus daily days 1-5 DRUG: Dexamethasone Premedication: Dexamethasone 20mg intravenously days 1-5 DRUG: Ondansetron Premedication: Ondansetron 16mg intravenously days 1-5

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Protocol Specified Chemotherapy

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

DRUG: Avastin

Every 28 Days: Avastin 5mg/kg iv days 1 and 15

DRUG: Fluorouracil

Every 28 Days: Fluorouracil 400mg/m^2 iv bolus daily days 1-5

DRUG: Doxorubicin

Every 28 Days: Doxorubicin 40mg/m^2 iv bolus day 1

DRUG: Streptozocin

Every 28 Days: Streptozocin 400mg/m2 iv bolus daily days 1-5

DRUG: Dexamethasone

Premedication: Dexamethasone 20mg intravenously days 1-5

DRUG: Ondansetron

Premedication: Ondansetron 16mg intravenously days 1-5

Primary Outcome Measures	Measure Description	Time Frame
Number of Participants With Progression Free Survival (PFS) at 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).	12 months

Secondary Outcome Measures	Measure Description	Time Frame
The Number of Participants With Radiographic Response	Objective Radiographic Response Rate (ORR). We planned to calculate the sum of complete response (CR) and partial response (PR) in target lesions.	2 years

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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)

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Genentech, Inc.

Investigators

PRINCIPAL_INVESTIGATOR: Larry Kvols, M.D., H. Lee Moffitt Cancer Center and Research Institute

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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