Tivantinib and Temsirolimus in Treating Patients With Solid Tumors That is Metastatic or Cannot be Removed By Surgery
This phase I trial studies to find the highest dose of tivantinib, when given in combination with temsirolimus that can be safely given for the treatment of the type of cancer that patients have. Tivantinib and temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Unspecified Adult Solid Tumor, Protocol Specific
Other: pharmacological study
Other: laboratory biomarker analysis
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 1 Study of ARQ 197 in Combination With Temsirolimus in Advanced Solid Tumors|
- MTD and RP2D of tivantinib in combination with temsirolimus defined as the highest safely tolerated dose where 0/6 or 1/6 patients experience a dose-limiting toxicity (DLT) and two or more patients have experienced a DLT at the next higher dose level [ Time Frame: First 35 days ] [ Designated as safety issue: No ]Categorized according to NCI Common Toxicity Criteria version 4.0.
- Adverse events and toxicities of tivantinib in combination with temsirolimus [ Time Frame: Assessed up to 4 weeks after completion of study treatment ] [ Designated as safety issue: No ]Categorized according to NCI Common Toxicity Criteria version 4.0. Summarized in terms of type, severity (grade 1-5), and dose level in tabular format. Wilson score method will be used to construct confidence intervals.
- Response rate validated by the RECIST criteria [ Time Frame: Assessed up to 4 weeks after completion of study treatment ] [ Designated as safety issue: No ]Summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease. Ninety-five percent confidence intervals will be constructed using the Wilson Score method.
- Pharmacokinetic analysis [ Time Frame: Days 1, 7, 8, 15 and 22 of course 1 and day 1 of courses 2 and 3 ] [ Designated as safety issue: No ]Plots of individual, mean, and median plasma concentration versus time will be presented where appropriate. The comparison of PK parameters between dose levels will be performed using a two-sample t-test.
|Study Start Date:||May 2012|
|Estimated Primary Completion Date:||October 2014 (Final data collection date for primary outcome measure)|
Experimental: Treatment (tivantinib, temsirolimus)
Patients receive tivantinib PO BID and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22 (days 8, 15, 22, and 29 of course 1). Courses repeat every 28 days (35 days in course 1) in the absence of disease progression or unacceptable toxicity.
Given PODrug: temsirolimus
Given IVOther: pharmacological study
Correlative studiesOther: laboratory biomarker analysis
I. To determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of ARQ197 (tivantinib) in combination with temsirolimus in adult subjects with advanced solid tumors who are extensive cytochrome P450 2C19 (CYP2C19) metabolizers.
I. To characterize the tolerability and/or MTD of ARQ 197 and in combination with temsirolimus in adult subjects who are poor CYP2C19 metabolizers (CYP2C19*2/*2, *2/*3 or *3/*3 polymorphisms).
II. To identify the pharmacokinetic parameters of ARQ 197 after a single dose and at steady state in extensive and poor CYP2C19 metabolizers.
III. To assess the steady state pharmacokinetics of ARQ 197 alone and in combination with temsirolimus.
IV. To determine impact of CYP3A4/5 polymorphisms on ARQ 197 pharmacokinetic parameters.
V. To determine the pharmacokinetics of temsirolimus and its active metabolite sirolimus in combination with ARQ 197 and compare to historical pharmacokinetic data.
VI. To determine impact of CYP3A4/5 polymorphisms on temsirolimus pharmacokinetic parameters.
VII. To describe the dose-limiting toxicities and determine the safety profile of the combination of ARQ 197 and temsirolimus.
VIII. To evaluate the preliminary anti-tumor activity of ARQ197 and temsirolimus in patients with advanced solid tumors.
IX. To assess for pharmacodynamic evidence of c-Met and mammalian target of rapamycin (mTOR) inhibition in peripheral blood mononuclear cells (PBMCs) over the course of therapy.
X. To correlate archived tumor tissue expression of c-Met with objective response to ARQ 197 and temsirolimus therapy.
OUTLINE: This is a dose-escalation study of tivantinib.
Patients receive tivantinib orally (PO) twice daily (BID) and temsirolimus intravenously (IV) over 30 minutes on days 1, 8, 15, and 22 (days 8, 15, 22, and 29 of course 1). Courses repeat every 28 days (35 days in course 1) in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for at least 4 weeks.
|United States, Wisconsin|
|University of Wisconsin Hospital and Clinics||Recruiting|
|Madison, Wisconsin, United States, 53792|
|Contact: Kari B. Wisinski 608-262-2876 email@example.com|
|Principal Investigator: Kari B. Wisinski|
|Principal Investigator:||Kari Wisinski||University of Wisconsin Hospital and Clinics|