A Phase I/II Study of AZD0530 in Combination With Gemcitabine in Patients With Advanced Pancreatic Cancer
- Determine the maximum tolerated dose of AZD0530 when given in combination with
gemcitabine in patients with unresectable, locally advanced or metastatic pancreatic
- Determine the safety and tolerability of this regimen in these patients.
- Determine toxicity profile and dose-limiting toxicity of this regimen in these
- Determine pharmacokinetic profile of this regimen in these patients.
- Correlate the toxicity profile with the pharmacokinetics of this regimen in these
- 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
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.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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
Malcolm J. Moore, MD
Princess Margaret Hospital, Canada
United States: Federal Government