Tivantinib and Topotecan Hydrochloride in Treating Patients With Advanced or Metastatic Solid Tumors or Recurrent Small Cell Lung Cancer
This phase I trial studies the side effects and best dose of tivantinib given together with topotecan hydrochloride in treating patients with advanced or metastatic solid tumors or recurrent small cell lung cancer. Tivantinib and topotecan hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Recurrent Small Cell Lung Cancer
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 30 days after completion of study treatment ] [ 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 (RECIST) version 1.1 [ Time Frame: Up to 4 weeks after completion of study treatment ] [ 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 patients with small cell lung cancer (SCLC) treated at the RP2D, the response rate will be estimated in 2 ways: (1) primary analysis will include all eligible patients who began treatment, and (2) a secondary analysis will include eligible patients who completed 2 courses or who came off treatment for disease progression prior to completing the second course.
- 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 18 months after completion of study treatment ] [ Designated as safety issue: No ]PFS will be reported for all patients. For patients with SCLC, PFS summarized using standard descriptive statistics (Kaplan-Meier plots with point estimates and standard errors at 6, 12, and 18 months). Patients will be classified by their response to first-line platinum-based chemotherapy. For patients who had progression of their cancer 90 days after completion of platinum-based chemotherapy will be classified as having "platinum-refractory" disease; patients with progression 90 days after completion of platinum-based chemotherapy will be classified as having "platinum-sensitive" disease."
- Overall survival (OS) [ Time Frame: The time from start of treatment until death due to any cause, assessed up to 18 months after completion of study treatment ] [ Designated as safety issue: No ]OS will be reported for all patients. For patients with SCLC, OS will be summarized using standard descriptive statistics (Kaplan-Meier plots with point estimates and standard errors at 6, 12, and 18 months).
- 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 and topotecan hydrochloride)
Patients receive tivantinib PO BID on days 1-21 and topotecan hydrochloride IV over 30 minutes on days 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Given PODrug: topotecan hydrochloride
Given IVOther: laboratory biomarker analysis
Correlative studiesOther: pharmacological study
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 and topotecan hydrochloride IV over 30 minutes on days 1-5. 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.
|United States, California|
|City of Hope||Recruiting|
|Duarte, California, United States, 91010|
|Contact: Marianna Koczywas 626-256-4673 firstname.lastname@example.org|
|Principal Investigator: Marianna Koczywas|
|USC Norris Comprehensive Cancer Center||Recruiting|
|Los Angeles, California, United States, 90033|
|Contact: Barbara J. Gitlitz 323-865-3900 email@example.com|
|Principal Investigator: Barbara J. Gitlitz|
|UC Davis Comprehensive Cancer Center||Recruiting|
|Sacramento, California, United States, 95817|
|Contact: David R. Gandara 916-734-3771 firstname.lastname@example.org|
|Principal Investigator: David R. Gandara|
|City of Hope- South Pasadena Cancer Center||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 email@example.com|
|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 firstname.lastname@example.org|
|Principal Investigator: Chandra P. Belani|
|University of Pittsburgh Cancer Institute||Recruiting|
|Pittsburgh, Pennsylvania, United States, 15232|
|Contact: Ahmad A. Tarhini 412-648-6507 email@example.com|
|Principal Investigator: Ahmad A. Tarhini|
|Principal Investigator:||Barbara Gitlitz||Beckman Research Institute|