Tivantinib in Treating Patients With Previously Treated Malignant Mesothelioma
This phase II trial studies how well tivantinib works in treating patients with previously treated malignant mesothelioma. Tivantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Recurrent Malignant Mesothelioma
Stage II Malignant Mesothelioma
Stage III Malignant Mesothelioma
Stage IV Malignant Mesothelioma
Other: laboratory biomarker analysis
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 2 Study of ARQ 197 in Patients With Previously-Treated Malignant Mesothelioma|
- Objective radiologic response rate (complete or partial response) assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
- Time to disease progression [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]Analyzed using the Kaplan-Meier method.
- Overall survival [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]Analyzed using the Kaplan-Meier method.
- Incidence of adverse events, graded per NCI CTCAE version 4 [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]Toxicity will be summarized by type and grade.
- Change in baseline levels of continuous or ordinal markers (e.g., serum HGF/MET IHC) between responders and non-responders [ Time Frame: Baseline to 1 year ] [ Designated as safety issue: No ]Fisher's exact test will be performed for binary variables (e.g., presence/absence of MET gene amplification). Paired t-tests or Wilcoxon signed-ranks test, whichever is appropriate, will be used to examine the changes with treatment in the laboratory correlates that are continuous and McNemar's test will be used for binary markers.
- Change in serum HGF or MET IHC and tumor size change (percent reduction in sum of longest diameters) [ Time Frame: Baseline to 1 year ] [ Designated as safety issue: No ]Will be evaluated by Spearman's rank correlation coefficient.
- Association between baseline HGF, MET gene amplification, MET IHC and PFS [ Time Frame: Baseline to 1 year ] [ Designated as safety issue: No ]Will be evaluated using the Cox regression model.
|Study Start Date:||January 2013|
|Estimated Primary Completion Date:||February 2015 (Final data collection date for primary outcome measure)|
Experimental: Treatment (tivantinib)
Patients receive tivantinib PO BID. Treatment continues in the absence of disease progression or unacceptable toxicity.
Other Name: ARQ 197Other: laboratory biomarker analysis
I. To determine the objective response rate of patients with malignant mesothelioma who are treated with ARQ 197 (tivantinib).
I. To determine the progression-free survival of patients with malignant mesothelioma who are treated with ARQ 197.
II. To determine the toxicity experienced by patients with malignant mesothelioma who are treated with ARQ 197.
III. To determine median and overall survival of patients with malignant mesothelioma who are treated with ARQ 197.
I. To determine the frequency of mesenchymal-epithelial transition (MET) gene amplification in malignant mesothelioma patient tumor samples, and to correlate the results with MET immunohistochemistry (IHC).
II. To determine whether MET gene amplification results in increased sensitivity to ARQ 197 as observed by improved clinical outcomes (response rate [RR] and progression free survival [PFS]) compared to those without MET gene over-expression/amplification.
III. To determine whether high baseline serum hepatocyte growth factor (HGF), as well as changes in serum HGF during treatment at pre-defined early time points, correlate with treatment efficacy and clinical outcome, as measured by response rate and progression-free survival.
IV. To identify mutations by sequencing of specific areas of the MET gene in tumor samples (semaphorin [SEMA], jumonji [JM] and tyrosine kinase domains).
V. To perform immunohistochemistry (IHC) of mesothelioma tumors for HGF, MET and phosphorylated (p)-MET (pY1003 and pY1230/34/35).
VI. To assess serum HGF and serum soluble MET levels by enzyme linked immunosorbent assay (ELISA) (R&D systems) pre-treatment, after 2 cycles and at disease progression.
Patients receive tivantinib orally (PO) twice daily (BID). Treatment continues in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 1 year.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01861301
|United States, California|
|City of Hope||Recruiting|
|Duarte, California, United States, 91010|
|Contact: Marianna Koczywas 800-826-4673 firstname.lastname@example.org|
|Principal Investigator: Marianna Koczywas|
|University of Southern California/Norris Cancer Center||Recruiting|
|Los Angeles, California, United States, 90033|
|Contact: Barbara J. Gitlitz 323-865-0451 email@example.com|
|Principal Investigator: Barbara J. Gitlitz|
|University of California at Davis Cancer Center||Recruiting|
|Sacramento, California, United States, 95817|
|Contact: David R. Gandara 916-734-3089|
|Principal Investigator: David R. Gandara|
|City of Hope South Pasadena||Recruiting|
|South Pasadena, California, United States, 91030|
|Contact: Stephen C. Koehler 626-396-2900|
|Principal Investigator: Stephen C. Koehler|
|United States, Illinois|
|University of Chicago||Recruiting|
|Chicago, Illinois, United States, 60637|
|Contact: Hedy L. Kindler 773-702-0360 firstname.lastname@example.org|
|Principal Investigator: Hedy L. Kindler|
|Chicago, Illinois, United States, 60611|
|Contact: Timothy M. Kuzel 312-695-1301 email@example.com|
|Principal Investigator: Timothy M. Kuzel|
|Decatur Memorial Hospital||Recruiting|
|Decatur, Illinois, United States, 62526|
|Contact: James L. Wade 217-876-4740 firstname.lastname@example.org|
|Principal Investigator: James L. Wade|
|NorthShore University HealthSystem-Evanston Hospital||Recruiting|
|Evanston, Illinois, United States, 60201|
|Contact: Bruce E. Brockstein 847-570-1381 email@example.com|
|Principal Investigator: Bruce E. Brockstein|
|Ingalls Memorial Hospital||Recruiting|
|Harvey, Illinois, United States, 60426|
|Contact: Sulochana D. Yalavarthi 708-915-4673 firstname.lastname@example.org|
|Principal Investigator: Mark F. Kozloff|
|Principal Investigator: Sulochana D. Yalavarthi|
|Peoria, Illinois, United States, 61615|
|Contact: James A. Knost 309-243-3000 email@example.com|
|Principal Investigator: Sachdev P. Thomas|
|Principal Investigator: James A. Knost|
|Southern Illinois University||Recruiting|
|Springfield, Illinois, United States, 62702|
|Contact: Krishna A. Rao 217-545-5817 firstname.lastname@example.org|
|Principal Investigator: Krishna A. Rao|
|United States, Indiana|
|Fort Wayne Medical Oncology and Hematology Inc-Parkview||Recruiting|
|Fort Wayne, Indiana, United States, 46845|
|Contact: Sreenivasa R. Nattam 260-484-8830 email@example.com|
|Principal Investigator: Sreenivasa R. Nattam|
|Indiana University Medical Center||Recruiting|
|Indianapolis, Indiana, United States, 46202|
|Contact: Noah M. Hahn 317-278-6871 firstname.lastname@example.org|
|Principal Investigator: Noah M. Hahn|
|United States, Michigan|
|University of Michigan||Recruiting|
|Ann Arbor, Michigan, United States, 48109|
|Contact: Maha H. Hussain 800-865-1125 email@example.com|
|Principal Investigator: Maha H. Hussain|
|Wayne State University/Karmanos Cancer Institute||Recruiting|
|Detroit, Michigan, United States, 48201|
|Contact: Shirish M. Gadgeel 313-576-9363 firstname.lastname@example.org|
|Principal Investigator: Shirish M. Gadgeel|
|United States, Missouri|
|Saint John's Mercy Medical Center||Recruiting|
|Saint Louis, Missouri, United States, 63141|
|Contact: Bethany G. Sleckman 913-948-5588|
|Principal Investigator: Bethany G. Sleckman|
|United States, Pennsylvania|
|Penn State Milton S Hershey Medical Center||Recruiting|
|Hershey, Pennsylvania, United States, 17033-0850|
|Contact: Chandra P. Belani 717-531-3779 CTO@hmc.psu.edu|
|Principal Investigator: Chandra P. Belani|
|University of Pittsburgh Cancer Institute||Recruiting|
|Pittsburgh, Pennsylvania, United States, 15232|
|Contact: Mark A. Socinski 412-623-4083 email@example.com|
|Principal Investigator: Mark A. Socinski|
|Principal Investigator:||Hedy Kindler||University of Chicago|