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

Phase II Study of 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.

Study Overview

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

Study Type

Interventional

Enrollment (Actual)

1

Phase

  • Phase 2

Contacts and Locations

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

Study Locations

    • Florida
      • Tampa, Florida, United States, 33612
        • H. Lee Moffitt Cancer Center and Research Institute

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.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

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

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

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

Every 28 Days: Avastin 5mg/kg iv days 1 and 15
Other Names:
  • bevacizumab
Every 28 Days: Fluorouracil 400mg/m^2 iv bolus daily days 1-5
Other Names:
  • 5-FU
  • Efudex
  • Fluoroplex
Every 28 Days: Doxorubicin 40mg/m^2 iv bolus day 1
Other Names:
  • Adriamycin®
Every 28 Days: Streptozocin 400mg/m2 iv bolus daily days 1-5
Other Names:
  • Zanosar®
Premedication: Dexamethasone 20mg intravenously days 1-5
Other Names:
  • Decadron
Premedication: Ondansetron 16mg intravenously days 1-5
Other Names:
  • Zofran

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Progression Free Survival (PFS) at 12 Months
Time Frame: 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

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

Collaborators and Investigators

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

Collaborators

Investigators

  • Principal Investigator: Larry Kvols, M.D., H. Lee Moffitt Cancer Center and Research Institute

Publications and helpful links

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

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 Major Dates

Study Start

August 1, 2007

Primary Completion (Actual)

March 1, 2008

Study Completion (Actual)

March 1, 2008

Study Registration Dates

First Submitted

January 24, 2008

First Submitted That Met QC Criteria

February 6, 2008

First Posted (Estimate)

February 7, 2008

Study Record Updates

Last Update Posted (Actual)

March 23, 2017

Last Update Submitted That Met QC Criteria

February 20, 2017

Last Verified

March 1, 2011

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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