AZD2281 and Irinotecan in Treating Patients With Locally Advanced or Metastatic Colorectal Cancer
Condition: Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      RATIONALE: AZD2281 may stop the growth of tumor cells by blocking some of the enzymes needed
      for cell growth. Drugs used in chemotherapy, such as irinotecan, work in different ways to
      stop the growth of tumor cells, either by killing the cells or by stopping them from
      dividing. Giving AZD2281 together with irinotecan may kill more tumor cells.

      PURPOSE: This phase I trial is studying the side effects and best dose of AZD2281 and
      irinotecan in treating patients with locally advanced or metastatic colorectal cancer.
    

Detailed description: 
      OBJECTIVES:

        -  To determine the recommended phase II dose of AZD2281 and irinotecan hydrochloride in
           patients with locally advanced or metastatic colorectal cancer.

        -  To determine the safety, tolerability, toxicity profile, dose-limiting toxicities, and
           pharmacokinetic profile of this regimen.

        -  To assess the correlation, if any, between the toxicity profile and pharmacokinetics of
           this regimen.

        -  To assess, preliminarily, the antitumor activity of this regimen in patients with
           measurable disease.

        -  To demonstrate the pharmacodynamic activity of this regimen by establishing its effects
           in tumor biopsies, cheek swabs, and blood samples.

        -  To assess the correlation, if any, between patients with tumors demonstrating
           microsatellite instability and antitumor activity and pharmacodynamic effects of this
           regimen.

        -  To investigate the impact of common genetic polymorphisms of genes of relevant pathways
           (drug metabolism, DNA repair, and apoptosis) on outcome and toxicity as well as other
           pharmacodynamic effects.

      OUTLINE: This is a multicenter, dose-escalation study of AZD2281 and irinotecan
      hydrochloride.

        -  Part I: Patients receive oral AZD2281 twice a day on days -7 to 21 in course 1 and on
           days 1-21 in all subsequent courses. Patients also receive irinotecan hydrochloride IV
           over 90 minutes on day 1. Courses repeat every 21 days (course 1 is 28 days) until the
           maximum tolerated dose is determined in the absence of disease progression or
           unacceptable toxicity.

        -  Part II: Patients then receive oral AZD2281 once daily on days 1-5 and irinotecan
           hydrochloride IV over 90 minutes on day 3 at the maximum tolerated dose determined in
           Part I. Courses repeat every 14 days in the absence of disease progression or
           unacceptable toxicity.

      Patients undergo cheek swabs, tumor tissue, and blood sample collection periodically for
      pharmacokinetic, pharmacodynamic, and correlative studies.

      After completion of study treatment, patients are followed at 4 weeks and then every 3 months
      thereafter.
    

Intervention name(s): irinotecan hydrochloride; olaparib
Intervention type(s): Drug; Drug
Intervention description(s): In Part A, a continuous oral AZD2281 dose will be given in combination with irinotecan given as a 90 minute infusion on day 1 every 21 days. In Part B, AZD2281 will be given on days 1-5 and irinotecan as a 90 minute infusion on day 3 each cycle. Cycles are repeated every 14 days.; In Part A, a continuous oral AZD2281 dose will be given in combination with irinotecan given as a 90 minute infusion on day 1 every 21 days. In Part B, AZD2281 will be given on days 1-5 and irinotecan as a 90 minute infusion on day 3 each cycle. Cycles are repeated every 14 days.
Intervention MeSH terms: Irinotecan; Olaparib
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: recurrent colon cancer; stage IV colon cancer; recurrent rectal cancer; stage IV rectal cancer; stage III rectal cancer; stage III colon cancer