AZD0530 and Gemcitabine in Locally Advanced/Metastatic Pancreatic Cancer That Cannot Be Removed By Surgery
Condition: Pancreatic Cancer
MeSH terms: Pancreatic Neoplasms
Study type: Interventional
Phase: Phase 1/Phase 2

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.
    

Intervention name(s): AZD0530; gemcitabine hydrochloride
Intervention type(s): Drug; Drug
Intervention description(s): Taken daily every 4 weeks; 1000mg/m2 IV weekly
Intervention MeSH terms: Gemcitabine; Saracatinib
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: adenocarcinoma of the pancreas; stage III pancreatic cancer; recurrent pancreatic cancer; stage IV pancreatic cancer