Irinotecan and Alisertib in Treating Patients With Advanced Solid Tumors or Colorectal Cancer
Mucinous Adenocarcinoma of the Colon
Mucinous Adenocarcinoma of the Rectum
Recurrent Colon Cancer
Recurrent Rectal Cancer
Signet Ring Adenocarcinoma of the Colon
Signet Ring Adenocarcinoma of the Rectum
Stage IIIA Colon Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Drug: irinotecan hydrochloride
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Study of the Combination of Irinotecan and MLN8237 in Advanced Solid Tumors With Emphasis on Colorectal Cancer|
- 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 ] [ Designated as safety issue: Yes ]
- Incidence of toxicities observed at each dose level graded according to NCI CTCAE version 4.0 [ Time Frame: Up to 30 days ] [ Designated as safety issue: Yes ]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 ] [ Designated as safety issue: No ]
- Survival [ Time Frame: Up to 30 days ] [ Designated as safety issue: No ]Summarized with Kaplan-Meier plots.
- Time to failure [ Time Frame: Up to 30 days ] [ Designated as safety issue: No ]Summarized with Kaplan-Meier plots.
|Study Start Date:||August 2013|
|Estimated Study Completion Date:||December 2016|
|Estimated Primary Completion Date:||August 2016 (Final data collection date for primary outcome measure)|
Experimental: Treatment (irinotecan, alisertib)
Patients receive irinotecan hydrochloride IV over 30 minutes on days 1 and 8 and alisertib PO BID on days 1-3 and 8-10. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: irinotecan hydrochloride
Other Names:Drug: alisertib
I. To investigate the feasibility and safety of MLN8237 (alisertib) when given in combination with irinotecan (irinotecan hydrochloride) to patients with advanced solid tumors.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01923337
|United States, California|
|UC Davis Comprehensive Cancer Center|
|Sacramento, California, United States, 95817|
|Principal Investigator:||Thomas Semrad||UC Davis Comprehensive Cancer Center|