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

This study has been terminated.
(Development of new chemotherapy standard of care for treatment rendered the trial obsolete.)
Sponsor:
Collaborator:
Genentech
Information provided by:
H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:
NCT00609765
First received: January 24, 2008
Last updated: March 24, 2011
Last verified: March 2011
History of Changes
  Purpose

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.


Condition Intervention Phase
Pancreatic Cancer
 Drug: Avastin
Drug: Fluorouracil
Drug: Doxorubicin
Drug: Streptozocin
Drug: Dexamethasone
Drug: Ondansetron
 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Avastin, Fluorouracil, Doxorubicin and Streptozocin in Locally Advanced and Metastatic Pancreatic Endocrine Tumors

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:

Primary Outcome Measures:
  • Number of Participants With Progression Free Survival (PFS) at 12 Months [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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:
  • The Number of Participants With Radiographic Response [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Objective Radiographic Response Rate (ORR). We planned to calculate the sum of complete response (CR) and partial response (PR) in target lesions.


Enrollment: 1
Study Start Date: August 2007
Study Completion Date: March 2008
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Other Name: bevacizumab
Drug: Fluorouracil
Every 28 Days: Fluorouracil 400mg/m^2 iv bolus daily days 1-5
Other Names:
  • Fluoroplex
  • 5-FU
  • Efudex
Drug: Doxorubicin
Every 28 Days: Doxorubicin 40mg/m^2 iv bolus day 1
Other Name: Adriamycin®
Drug: Streptozocin
Every 28 Days: Streptozocin 400mg/m2 iv bolus daily days 1-5
Other Name: Zanosar®
Drug: Dexamethasone
Premedication: Dexamethasone 20mg intravenously days 1-5
Other Name: Decadron
Drug: Ondansetron
Premedication: Ondansetron 16mg intravenously days 1-5
Other Name: Zofran

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
  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00609765

Locations
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States, 33612
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Genentech
Investigators
Principal Investigator: Larry Kvols, M.D. H. Lee Moffitt Cancer Center and Research Institute
Principal Investigator: Jonathan Strosberg, M.D. H. Lee Moffitt Cancer Center and Research Institute
  More Information

No publications provided

Responsible Party: Larry Kvols, M.D., H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT00609765     History of Changes
Other Study ID Numbers: MCC-14961, AVF3915s
Study First Received: January 24, 2008
Results First Received: February 21, 2011
Last Updated: March 24, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
advanced
unresectable
metastatic
endocrine
tumors

Additional relevant MeSH terms:
Endocrine Gland Neoplasms
Pancreatic Neoplasms
Adenoma, Islet Cell
Neoplasms by Site
Neoplasms
Endocrine System Diseases
Digestive System Neoplasms
Digestive System Diseases
Pancreatic Diseases
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Dexamethasone acetate
Dexamethasone
Ondansetron
 Dexamethasone 21-phosphate
Bevacizumab
Doxorubicin
Fluorouracil
Streptozocin
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents

ClinicalTrials.gov processed this record on June 18, 2013