AZD0530 and Gemcitabine in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer That Cannot Be Removed By Surgery
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.
Drug: gemcitabine hydrochloride
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Study of AZD0530 in Combination With Gemcitabine in Patients With Advanced Pancreatic Cancer|
- Response (complete [CR] and partial response [PR] or stable disease [SD]) at 8 weeks [ Time Frame: 4 years ] [ Designated as safety issue: No ]Response is assessed every other cycle and will be reported on at final analysis
- Toxicity [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]Toxicity is assessed from the time of first treatment and final results will be reported at final analysis
|Study Start Date:||September 2005|
|Study Completion Date:||January 2012|
|Primary Completion Date:||January 2012 (Final data collection date for primary outcome measure)|
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00265876
|Canada, British Columbia|
|BCCA - Vancouver Cancer Centre|
|Vancouver, British Columbia, Canada, V5Z 4E6|
|Ottawa Health Research Institute - General Division|
|Ottawa, Ontario, Canada, K1H 8L6|
|Algoma District Cancer Program|
|Sault Ste. Marie, Ontario, Canada, P6B 0A8|
|Univ. Health Network-Princess Margaret Hospital|
|Toronto, Ontario, Canada, M5G 2M9|
|Study Chair:||Malcolm J. Moore, MD||Princess Margaret Hospital, Canada|
|Study Chair:||Sharlene Gill, MD||British Columbia Cancer Agency|