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AZD0530 and Gemcitabine in Locally Advanced/Metastatic Pancreatic Cancer That Cannot Be Removed By Surgery

Phase 1
Completed
Conditions
Pancreatic Cancer
Interventions
Registration Number
NCT00265876
Lead Sponsor
NCIC Clinical Trials Group
Brief Summary

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.

Detailed Description

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
34
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
AZD0530 + Gemcitabinegemcitabine hydrochloride-
AZD0530 + GemcitabineAZD0530-
Primary Outcome Measures
NameTimeMethod
Response (complete [CR] and partial response [PR] or stable disease [SD]) at 8 weeks4 years

Response is assessed every other cycle and will be reported on at final analysis

Secondary Outcome Measures
NameTimeMethod
Toxicity4 years

Toxicity is assessed from the time of first treatment and final results will be reported at final analysis

Trial Locations

Locations (4)

Univ. Health Network-Princess Margaret Hospital

🇨🇦

Toronto, Ontario, Canada

Ottawa Health Research Institute - General Division

🇨🇦

Ottawa, Ontario, Canada

Algoma District Cancer Program

🇨🇦

Sault Ste. Marie, Ontario, Canada

BCCA - Vancouver Cancer Centre

🇨🇦

Vancouver, British Columbia, Canada

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