Tivantinib and Topotecan Hydrochloride in Treating Patients With Advanced or Metastatic Solid Tumors
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.
Unspecified Adult Solid Tumor, Protocol Specific
Drug: topotecan hydrochloride
Other: laboratory biomarker analysis
Other: pharmacological study
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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 ] [ Designated as safety issue: Yes ]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.
- Tumor response as evaluated by Response Evaluation Criteria in Solid Tumors version 1.1 [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: No ]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.
- 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 ] [ Designated as safety issue: No ]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.
- Overall survival (OS) [ Time Frame: The time from start of treatment until death due to any cause, assessed up to 4 weeks ] [ Designated as safety issue: No ]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.
- 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) ] [ Designated as safety issue: No ]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.
- CYP2C19 genotype [ Time Frame: Baseline ] [ Designated as safety issue: No ]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.
|Study Start Date:||July 2012|
|Estimated Primary Completion Date:||July 2014 (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 Name: ARQ 197Drug: topotecan hydrochloride
Other Names:Biological: pegfilgrastim
Other Names:Other: laboratory biomarker analysis
Correlative studiesOther: pharmacological study
Other Name: pharmacological studies
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||Recruiting|
|Duarte, California, United States, 91010|
|Contact: Barbara J. Gitlitz 323-865-3900 email@example.com|
|Principal Investigator: Barbara J. Gitlitz|
|University of Southern California/Norris Cancer Center||Recruiting|
|Los Angeles, California, United States, 90033|
|Contact: James S. Hu 323-865-3900 firstname.lastname@example.org|
|Principal Investigator: James S. Hu|
|University of California at Davis Cancer Center||Recruiting|
|Sacramento, California, United States, 95817|
|Contact: David R. Gandara 916-734-3771 email@example.com|
|Principal Investigator: David R. Gandara|
|City of Hope South Pasadena||Recruiting|
|South Pasadena, California, United States, 91030|
|Contact: Stephen C. Koehler 626-396-2900 Skoehler@cohmg.com|
|Principal Investigator: Stephen C. Koehler|
|United States, Michigan|
|Barbara Ann Karmanos Cancer Institute||Recruiting|
|Detroit, Michigan, United States, 48201|
|Contact: Shirish M. Gadgeel 313-576-8753 firstname.lastname@example.org|
|Principal Investigator: Shirish M. Gadgeel|
|United States, Pennsylvania|
|Penn State Milton S Hershey Medical Center||Recruiting|
|Hershey, Pennsylvania, United States, 17033-0850|
|Contact: Chandra P. Belani 717-531-1078 email@example.com|
|Principal Investigator: Chandra P. Belani|
|University of Pittsburgh Cancer Institute||Recruiting|
|Pittsburgh, Pennsylvania, United States, 15232|
|Contact: Ahmad A. Tarhini 412-648-6507 firstname.lastname@example.org|
|Principal Investigator: Ahmad A. Tarhini|
|Principal Investigator:||Barbara Gitlitz||Beckman Research Institute|