Clinical trial NCT00609765: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Pancreatic Cancer
Keywords: advanced
unresectable
metastatic
endocrine
tumors
Lead sponsor: H. Lee Moffitt Cancer Center and Research Institute
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
First posted: 2008-02-07
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: Number of Participants With Progression Free Survival (PFS) at 12 Months
timeFrame: 12 months
Secondary outcomes:
measure: The Number of Participants With Radiographic Response
timeFrame: 2 years
Other outcomes:
Locations:
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
Study officials:
affiliation: H. Lee Moffitt Cancer Center and Research Institute
name: Larry Kvols, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: H. Lee Moffitt Cancer Center and Research Institute
name: Jonathan Strosberg, M.D.
role: PRINCIPAL_INVESTIGATOR
References: