This phase I trial studies the side effects and best dose of tivantinib and topotecan hydrochloride in treating patients with advanced or metastatic solid tumors. Tivantinib and topotecan hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PRIMARY OBJECTIVES: I. To establish the recommended phase 2 dose (RP2D) for the combination of ARQ 197 (tivantinib) and intravenous (IV) topotecan (topotecan hydrochloride). II. To describe the toxicities of ARQ 197 and IV topotecan at each dose studied. III. To characterize the pharmacokinetic behavior of ARQ 197 given concurrent use of IV topotecan. IV. To document all clinical responses to ARQ 197 with IV topotecan. OUTLINE: This is a dose-escalation study of tivantinib and topotecan hydrochloride. Patients receive tivantinib orally (PO) twice daily (BID) on days 1-21, topotecan hydrochloride IV over 30 minutes on days 1-5, and pegfilgrastim subcutaneously (SC) on day 6. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 4 weeks.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
17
City of Hope Comprehensive Cancer Center
Duarte, California, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States
City of Hope South Pasadena
Incidence of adverse events graded according to the NCI CTCAE version 4.0
The 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 CTCAE), attribution, time of onset (i.e. course number), duration, and reversibility or outcome. Tables will be created to summarize these toxicities and side effects by dose and by course.
Time frame: Up to 4 weeks
Tumor response as evaluated by Response Evaluation Criteria in Solid Tumors version 1.1
All responses will be reported; because of the potential heterogeneity of the patients, no attempt will be made to summarize these for the patients included in the dose escalation phase.
Time frame: Up to 4 weeks
Progression-free survival (PFS)
PFS will be reported; because of the potential heterogeneity of the patients, no attempt will be made to summarize these for the patients included in the dose escalation phase.
Time frame: The time from start of treatment until first evidence of disease progression or death due to any cause, assessed up to 4 weeks
Overall survival (OS)
OS will be reported; because of the potential heterogeneity of the patients, no attempt will be made to summarize these for the patients included in the dose escalation phase.
Time frame: The time from start of treatment until death due to any cause, assessed up to 4 weeks
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Given PO
Given IV
South Pasadena, California, United States
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, United States
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, United States