Avastin, Fluorouracil, Doxorubicin and Streptozocin in Locally Advanced and Metastatic Pancreatic Endocrine Tumors
Primary Purpose
Pancreatic Cancer
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Avastin
Fluorouracil
Doxorubicin
Streptozocin
Dexamethasone
Ondansetron
Sponsored by
About this trial
This is an interventional treatment trial for Pancreatic Cancer focused on measuring advanced, unresectable, metastatic, endocrine, tumors
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
Sites / Locations
- H. Lee Moffitt Cancer Center and Research Institute
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Protocol Specified Chemotherapy
Arm Description
Protocol Specified Chemotherapy Every 28 Days: Avastin, Fluorouracil, Doxorubicin, Streptozocin. Premedications: Dexamethasone, Ondansetron
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
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.
Full Information
NCT ID
NCT00609765
First Posted
January 24, 2008
Last Updated
February 20, 2017
Sponsor
H. Lee Moffitt Cancer Center and Research Institute
Collaborators
Genentech, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT00609765
Brief Title
Avastin, Fluorouracil, Doxorubicin and Streptozocin in Locally Advanced and Metastatic Pancreatic Endocrine Tumors
Official Title
Phase II Study of Avastin, Fluorouracil, Doxorubicin and Streptozocin in Locally Advanced and Metastatic Pancreatic Endocrine Tumors
Study Type
Interventional
2. Study Status
Record Verification Date
March 2011
Overall Recruitment Status
Terminated
Why Stopped
Development of new chemotherapy standard of care for treatment rendered the trial obsolete.
Study Start Date
August 2007 (undefined)
Primary Completion Date
March 2008 (Actual)
Study Completion Date
March 2008 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
H. Lee Moffitt Cancer Center and Research Institute
Collaborators
Genentech, Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Cancer
Keywords
advanced, unresectable, metastatic, endocrine, tumors
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
1 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Protocol Specified Chemotherapy
Arm Type
Experimental
Arm Description
Protocol Specified Chemotherapy Every 28 Days: Avastin, Fluorouracil, Doxorubicin, Streptozocin.
Premedications: Dexamethasone, Ondansetron
Intervention Type
Drug
Intervention Name(s)
Avastin
Other Intervention Name(s)
bevacizumab
Intervention Description
Every 28 Days: Avastin 5mg/kg iv days 1 and 15
Intervention Type
Drug
Intervention Name(s)
Fluorouracil
Other Intervention Name(s)
Fluoroplex, 5-FU, Efudex
Intervention Description
Every 28 Days: Fluorouracil 400mg/m^2 iv bolus daily days 1-5
Intervention Type
Drug
Intervention Name(s)
Doxorubicin
Other Intervention Name(s)
Adriamycin®
Intervention Description
Every 28 Days: Doxorubicin 40mg/m^2 iv bolus day 1
Intervention Type
Drug
Intervention Name(s)
Streptozocin
Other Intervention Name(s)
Zanosar®
Intervention Description
Every 28 Days: Streptozocin 400mg/m2 iv bolus daily days 1-5
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Other Intervention Name(s)
Decadron
Intervention Description
Premedication: Dexamethasone 20mg intravenously days 1-5
Intervention Type
Drug
Intervention Name(s)
Ondansetron
Other Intervention Name(s)
Zofran
Intervention Description
Premedication: Ondansetron 16mg intravenously days 1-5
Primary Outcome Measure Information:
Title
Number of Participants With Progression Free Survival (PFS) at 12 Months
Description
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).
Time Frame
12 months
Secondary Outcome Measure Information:
Title
The Number of Participants With Radiographic Response
Description
Objective Radiographic Response Rate (ORR). We planned to calculate the sum of complete response (CR) and partial response (PR) in target lesions.
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Larry Kvols, M.D.
Organizational Affiliation
H. Lee Moffitt Cancer Center and Research Institute
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jonathan Strosberg, M.D.
Organizational Affiliation
H. Lee Moffitt Cancer Center and Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
H. Lee Moffitt Cancer Center and Research Institute
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Avastin, Fluorouracil, Doxorubicin and Streptozocin in Locally Advanced and Metastatic Pancreatic Endocrine Tumors
We'll reach out to this number within 24 hrs