AZD2281 and Irinotecan in Treating Patients With Locally Advanced or Metastatic Colorectal Cancer
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.
Drug: irinotecan hydrochloride
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of AZD2281 in Combination With Irinotecan in Patients With Locally Advanced or Metastatic Incurable Colorectal Cancer|
- Recommended phase II dose of AZD2281 and irinotecan hydrochloride [ Time Frame: Nov 2011 ]End of study
- Safety [ Time Frame: Nov 2011 ]End of study
- Tolerability [ Time Frame: Nov 2011 ]End of study
- Dose-limiting toxicities [ Time Frame: 2011-May-28 ]Fatigue, Nausea, Dehydration and Anorexia.
- Pharmacokinetic profile [ Time Frame: Nov 2011 ]End of study
- Correlation, if any, between the toxicity profile and pharmacokinetics [ Time Frame: Nov 2011 ]End of study.
- Efficacy [ Time Frame: Nov 2011 ]End of study
- Pharmacodynamic outcomes [ Time Frame: Nov 2011 ]End of study.
|Study Start Date:||August 2007|
|Study Completion Date:||February 2015|
|Primary Completion Date:||September 2012 (Final data collection date for primary outcome measure)|
Drug: irinotecan hydrochloride
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00535353
|Ottawa Health Research Institute - General Division|
|Ottawa, Ontario, Canada, K1H 8L6|
|Univ. Health Network-Princess Margaret Hospital|
|Toronto, Ontario, Canada, M5G 2M9|
|Study Chair:||Eric X. Chen, MD, PhD||Princess Margaret Hospital, Canada|