Tivantinib and Topotecan Hydrochloride in Treating Patients With Advanced or Metastatic Solid Tumors
|Adult Solid Neoplasm||Other: Laboratory Biomarker Analysis Biological: Pegfilgrastim Other: Pharmacological Study Drug: Tivantinib Drug: Topotecan Hydrochloride||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Phase I Study of ARQ 197 in Combination With IV Topotecan in Advanced Solid Tumors With an Expansion Cohort in Small Cell Lung Cancer|
- Incidence of adverse events graded according to the NCI CTCAE version 4.0 [ Time Frame: Up to 4 weeks ]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.
- Overall survival (OS) [ Time Frame: The time from start of treatment until death due to any cause, assessed up to 4 weeks ]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.
- Progression-free survival (PFS) [ 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 ]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.
- Tumor response as evaluated by Response Evaluation Criteria in Solid Tumors version 1.1 [ Time Frame: Up to 4 weeks ]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.
- CYP2C19 genotype [ Time Frame: Baseline ]The association between CYP2C19 genotype and ARQ 197 levels, and toxicity will also be displayed and summarized. All data summaries based on pharmacodynamic studies will be descriptive and exploratory.
- Pharmacokinetics behavior of tivantinib given concurrently with topotecan hydrochloride [ Time Frame: At baseline, at 2, 3, 4, and 8 hours of day 1 and at 12 hours after evening dose of day 4 (on day 5) ]Summarized by dose level with simple summary statistics: means (possibly after transformation) or medians, ranges, and standard deviations (if numbers and distribution permit). Scatterplots will be used to explore possible associations between the dose and day 1 AUC, dose and levels on day 1 and day 5, and between these pharmacokinetic determinations and toxicity experienced (as reflected in the maximum grade of toxicity experienced). All data summaries based on pharmacokinetic studies will be descriptive and exploratory.
|Actual Study Start Date:||July 24, 2012|
|Estimated Primary Completion Date:||December 31, 2017 (Final data collection date for primary outcome measure)|
Experimental: Treatment (tivantinib, topotecan hydrochloride, pegfilgrastim)
Patients receive tivantinib PO BID on days 1-21, topotecan hydrochloride IV over 30 minutes on days 1-5, and pegfilgrastim SC on day 6. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studiesBiological: Pegfilgrastim
Other Names:Other: Pharmacological Study
Correlative studiesDrug: Tivantinib
Other Names:Drug: Topotecan Hydrochloride
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01654965
|United States, California|
|City of Hope Comprehensive Cancer Center|
|Duarte, California, United States, 91010|
|USC / Norris Comprehensive Cancer Center|
|Los Angeles, California, United States, 90033|
|University of California Davis Comprehensive Cancer Center|
|Sacramento, California, United States, 95817|
|City of Hope South Pasadena|
|South Pasadena, California, United States, 91030|
|United States, Michigan|
|Wayne State University/Karmanos Cancer Institute|
|Detroit, Michigan, United States, 48201|
|United States, Pennsylvania|
|Penn State Milton S Hershey Medical Center|
|Hershey, Pennsylvania, United States, 17033-0850|
|University of Pittsburgh Cancer Institute (UPCI)|
|Pittsburgh, Pennsylvania, United States, 15232|
|Principal Investigator:||Barbara Gitlitz||City of Hope Comprehensive Cancer Center|