Avastin, Fluorouracil, Doxorubicin and Streptozocin in Locally Advanced and Metastatic Pancreatic Endocrine Tumors
Overview[ - collapse ][ - ]
| 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 | Pancreatic Cancer |
| Intervention | Drug: Avastin Drug: Fluorouracil Drug: Doxorubicin Drug: Streptozocin Drug: Dexamethasone Drug: Ondansetron |
| Phase | Phase 2 |
| Sponsor | H. Lee Moffitt Cancer Center and Research Institute |
| Responsible Party | H. Lee Moffitt Cancer Center and Research Institute |
| ClinicalTrials.gov Identifier | NCT00609765 |
| First Received | January 24, 2008 |
| Last Updated | November 21, 2013 |
| Last verified | March 2011 |
Tracking Information[ + expand ][ + ]
| First Received Date | January 24, 2008 |
|---|---|
| Last Updated Date | November 21, 2013 |
| Start Date | August 2007 |
| Estimated Primary Completion Date | March 2008 |
| Current 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). |
| Current 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. |
Descriptive Information[ + expand ][ + ]
| 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 |
| 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 |
| Study Type | Interventional |
| Study Phase | Phase 2 |
| Study Design | Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment |
| Condition | Pancreatic Cancer |
| Intervention | Drug: Avastin Every 28 Days: Avastin 5mg/kg iv days 1 and 15 Other Names: bevacizumabDrug: Fluorouracil Every 28 Days: Fluorouracil 400mg/m^2 iv bolus daily days 1-5 Other Names:
Every 28 Days: Doxorubicin 40mg/m^2 iv bolus day 1 Other Names: Adriamycin®Drug: Streptozocin Every 28 Days: Streptozocin 400mg/m2 iv bolus daily days 1-5 Other Names: Zanosar®Drug: Dexamethasone Premedication: Dexamethasone 20mg intravenously days 1-5 Other Names: DecadronDrug: Ondansetron Premedication: Ondansetron 16mg intravenously days 1-5 Other Names: Zofran |
| Study Arm (s) | Experimental: Protocol Specified Chemotherapy Protocol Specified Chemotherapy Every 28 Days: Avastin, Fluorouracil, Doxorubicin, Streptozocin. Premedications: Dexamethasone, Ondansetron |
Recruitment Information[ + expand ][ + ]
| Recruitment Status | Terminated |
|---|---|
| Estimated Enrollment | 1 |
| Estimated Completion Date | March 2008 |
| Estimated Primary Completion Date | March 2008 |
| 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 |
| Gender | Both |
| Ages | 18 Years |
| Accepts Healthy Volunteers | No |
| Contacts | Not Provided |
| Location Countries | United States |
Administrative Information[ + expand ][ + ]
| NCT Number | NCT00609765 |
|---|---|
| Other Study ID Numbers | MCC-14961 |
| Has Data Monitoring Committee | Yes |
| Information Provided By | H. Lee Moffitt Cancer Center and Research Institute |
| Study Sponsor | H. Lee Moffitt Cancer Center and Research Institute |
| Collaborators | Genentech |
| Investigators | Principal Investigator: Larry Kvols, M.D. H. Lee Moffitt Cancer Center and Research InstitutePrincipal Investigator: Jonathan Strosberg, M.D. H. Lee Moffitt Cancer Center and Research Institute |
| Verification Date | March 2011 |
Locations[ + expand ][ + ]
| H. Lee Moffitt Cancer Center and Research Institute | Tampa, Florida, United States, 33612 |
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