RATIONALE: AZD0530 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving AZD0530 together with gemcitabine may kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of AZD0530 when given together with gemcitabine and to see how well they work in treating patients with locally advanced or metastatic pancreatic cancer that cannot be removed by surgery.
OBJECTIVES: Phase I * Determine the maximum tolerated dose of AZD0530 when given in combination with gemcitabine in patients with unresectable, locally advanced or metastatic pancreatic cancer. * Determine the safety and tolerability of this regimen in these patients. * Determine toxicity profile and dose-limiting toxicity of this regimen in these patients. * Determine pharmacokinetic profile of this regimen in these patients. * Correlate the toxicity profile with the pharmacokinetics of this regimen in these patients. Phase II * Determine the objective response rate (partial and complete response) and prolonged stable disease rate in patients treated with this regimen. * Determine the median survival, 1-year survival, response or stable disease duration, time to disease progression, clinical benefit response, and progression-free survival of patients treated with this regimen. * Determine the toxicity of this regimen in these patients. * Correlate changes in serum CTX levels (post-treatment vs baseline) with response and other clinical outcomes in patients treated with this regimen. OUTLINE: This is a phase I, open-label, multicenter, dose-escalation study of AZD0530 followed by a phase II study. * Phase I: Patients receive oral AZD0530 once daily on days 1-28 and gemcitabine IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients receive 2 additional courses after achieving complete response or stable partial response. Patients with ongoing stable disease receive up to 6 courses. Patients who discontinue gemcitabine due to unacceptable toxicity or who complete 6 courses of therapy may continue to receive AZD0530 alone in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of AZD0530 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD. * Phase II: Patients receive AZD0530 at the MTD determined in phase I and gemcitabine as in phase I. After completion of study treatment, patients are followed periodically. PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
34
Taken daily every 4 weeks
1000mg/m2 IV weekly
BCCA - Vancouver Cancer Centre
Vancouver, British Columbia, Canada
Ottawa Health Research Institute - General Division
Ottawa, Ontario, Canada
Algoma District Cancer Program
Sault Ste. Marie, Ontario, Canada
Univ. Health Network-Princess Margaret Hospital
Toronto, Ontario, Canada
Response (complete [CR] and partial response [PR] or stable disease [SD]) at 8 weeks
Response is assessed every other cycle and will be reported on at final analysis
Time frame: 4 years
Toxicity
Toxicity is assessed from the time of first treatment and final results will be reported at final analysis
Time frame: 4 years
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.