Clinical Trial: Alisertib and Gemcitabine Hydrochloride in Treating Patients With Solid Tumors or Pancreatic Cancer

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

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

Brief Summary: This phase I trial studies the side effects and the best dose of alisertib when given together with gemcitabine hydrochloride in treating patients with solid tumors or pancreatic cancer that is metastatic or cannot be removed by surgery. Alisertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving alisertib with gemcitabine hydrochloride may be an effective treatment for solid tumors or pancreatic cancer.

Detailed Summary:

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

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

II. To obtain preliminary evidence of efficacy as judged by response rate and progression-free survival for this combination.

III. To investigate the pharmacokinetics of MLN8237 given in combination with gemcitabine in an expanded cohort of patients with pancreatic cancer.

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

Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on days 1, 8, and 15 and alisertib orally (PO) twice daily (BID) on days 1-3, 8-10, and 15-17. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Current Primary Outcome: Dose-limiting toxicity (DLT) defined as any related (possibly, probably, or definitely) grade 3 non-hematological toxicity or any attributable grade 4 toxicity graded according to the National Cancer Institute (NCI) CTCAE version 4.0 [ Time Frame: Up to 21 days ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Incidence of adverse events graded according to NCI CTCAE version 4.0 [ Time Frame: Up to 30 days after completion of treatment ]
  Toxicities observed at each dose level 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 or outcome. Frequencies will be reported, with exact 95% confidence intervals. Tables will be created to summarize these toxicities and side effects by dose and by course.
• Response rate according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 [ Time Frame: Assessed up to 2 years ]
  Survival will be summarized with Kaplan-Meier plots to describe the outcome of patients treated on this protocol. Median survival time will be estimated using standard life table methods.
• Progression Free Survival [ Time Frame: Assessed up to 2 years ]
  Summarized with Kaplan-Meier plots. Median survival time will be estimated using standard life table methods.
• Maximum-tolerated dose (MTD) defined as the maximum dose level at which less than 2 patients experience DLT graded according to NCI CTCAE version 4.0 [ Time Frame: 21 days ]

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 2018
Last Updated: April 27, 2017
Last Verified: April 2017