Clinical Trial: Irinotecan and Alisertib in Treating Patients With Advanced Solid Tumors or Colorectal Cancer

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Phase I Study of the Combination of Irinotecan and MLN8237 in Advanced Solid Tumors With Emphasis on Colorectal Cancer

Brief Summary: This phase I trial studies the side effects and best dose of alisertib when given together with irinotecan hydrochloride in treating patients with advanced solid tumors or colorectal cancer. Irinotecan hydrochloride and alisertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To investigate the feasibility and safety of MLN8237 (alisertib) when given in combination with irinotecan (irinotecan hydrochloride) to patients with advanced solid tumors.

SECONDARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of MLN8237 when given in combination with irinotecan to patients with advanced solid tumors and to recommend a phase II dose for the combination.

II. To obtain preliminary evidence of efficacy for this combination. III. To compare the pharmacokinetics of SN-38 (the active metabolite of irinotecan) with and without concurrent administration of MLN8237 in an expanded cohort of patients with advanced colorectal cancer.

OUTLINE: This is a dose-escalation study of alisertib.

Patients receive irinotecan hydrochloride intravenously (IV) over 30 minutes on days 1 and 8 and alisertib orally (PO) twice daily (BID) on days 1-3 and 8-10. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.


Sponsor: University of California, Davis

Current Primary Outcome: MTD, defined as the highest dose tested in which fewer than 33% of patients experience dose-limiting toxicity (DLT) attributable to the study drugs, graded using the National Cancer Institute (NCI) CTCAE version 4.0 [ Time Frame: Up to day 21 ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Incidence of toxicities observed at each dose level graded according to NCI CTCAE version 4.0 [ Time Frame: Up to 30 days ]
    Will be summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity (by grade and nadir or maximum values for the laboratory measures), time of onset (i.e. course number), duration, and reversibility of outcome. Tables will be created to summarize these toxicities and side effects by dose and by course.
  • Response rates, as determined by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 [ Time Frame: Up to 30 days ]
  • Survival [ Time Frame: Up to 30 days ]
    Summarized with Kaplan-Meier plots.
  • Time to failure [ Time Frame: Up to 30 days ]
    Summarized with Kaplan-Meier plots.


Original Secondary Outcome: Same as current

Information By: University of California, Davis

Dates:
Date Received: August 13, 2013
Date Started: August 2013
Date Completion: December 2017
Last Updated: December 20, 2016
Last Verified: December 2016