Tivantinib in Treating Younger Patients With Relapsed or Refractory Solid Tumors
This phase I trial studies the side effects and best dose of tivantinib in treating younger patients with solid tumors that have returned after a period of improvement or have not responded to treatment. Tivantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Childhood Solid Neoplasm
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 the c-Met Inhibitor, Tivantinib (ARQ 197) in Children With Relapsed or Refractory Solid Tumors|
- MTD defined as the maximum dose at which fewer than one-third of patients experience dose-limiting toxicity (DLT) using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
- Pharmacokinetic (PK) parameters of tivantinib [ Time Frame: Pre-dose, 1, 2, 4, 6 and 8-12 hours day 1 of course 1; pre-dose day 1 of course 2 ] [ Designated as safety issue: No ]The PK parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).
- Disease response assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria [ Time Frame: Up to 30 days after completion of study treatment ] [ Designated as safety issue: No ]Will be reported descriptively.
- CYP450 polymorphisms [ Time Frame: Baseline ] [ Designated as safety issue: No ]Relationships between CYP450 polymorphisms and pharmacokinetics and toxicity will be explored.
- Tumor c-met expression [ Time Frame: Baseline ] [ Designated as safety issue: No ]Relationships between tumor c-met expression and response will be explored.
|Study Start Date:||October 2012|
|Estimated Primary Completion Date:||May 2015 (Final data collection date for primary outcome measure)|
Experimental: Treatment (tivantinib)
Patients receive tivantinib PO BID on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Other Names:Other: Pharmacological Study
Other Name: pharmacological studiesOther: Laboratory Biomarker Analysis
I. To estimate the maximum tolerated dose (MTD) and/or recommended phase 2 dose of tivantinib administered orally twice daily to children with refractory solid tumors.
II. To define and describe the toxicities of tivantinib administered on this schedule.
III. To characterize the pharmacokinetics of tivantinib (capsule as well as powder formulation) in children with refractory cancer.
I. To preliminarily define the antitumor activity of tivantinib within the confines of a phase 1 study.
II. To preliminarily investigate whether cytochrome P450 (CYP450) polymorphisms impact pharmacokinetics or toxicity of tivantinib.
III. To preliminarily investigate whether tumor c-Met and/or hepatocyte growth factor (HGF) expression or downstream c-Met signaling correlate with clinical response to tivantinib.
OUTLINE: This is a dose-escalation study.
Patients receive tivantinib orally (PO) twice daily (BID) on days 1-28. Treatment repeats every 28 days for up to 12 courses 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: NCT01725191
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|Principal Investigator:||James Geller||COG Phase I Consortium|