Pancreatic Cancer
Conditions
Keywords
advanced, unresectable, metastatic, 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
Interventions
DRUGAvastin
Every 28 Days: Avastin 5mg/kg iv days 1 and 15
DRUGFluorouracil
Every 28 Days: Fluorouracil 400mg/m\^2 iv bolus daily days 1-5
DRUGDoxorubicin
Every 28 Days: Doxorubicin 40mg/m\^2 iv bolus day 1
DRUGStreptozocin
Every 28 Days: Streptozocin 400mg/m2 iv bolus daily days 1-5
DRUGDexamethasone
Premedication: Dexamethasone 20mg intravenously days 1-5
DRUGOndansetron
Premedication: Ondansetron 16mg intravenously days 1-5
Sponsors
Genentech, Inc.
H. Lee Moffitt Cancer Center and Research Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Progression Free Survival (PFS) at 12 Months | 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
| Measure | Time frame | Description |
|---|---|---|
| The Number of Participants With Radiographic Response | 2 years | Objective Radiographic Response Rate (ORR). We planned to calculate the sum of complete response (CR) and partial response (PR) in target lesions. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Chemotherapy Prospective, single arm, Phase II | 1 |
| Total | 1 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Study ended prior to 12 months | 1 |
Baseline characteristics
| Characteristic | Chemotherapy |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Region of Enrollment United States | 1 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 1 |
| serious Total, serious adverse events | 0 / 1 |
Outcome results
Primary
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).
Time frame: 12 months
Population: Per protocol at 12 months
Secondary
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.
Time frame: 2 years