Tivantinib in Treating Patients With Previously Treated Malignant Mesothelioma
Recurrent Malignant Mesothelioma
Stage II Pleural Mesothelioma
Stage III Pleural Mesothelioma
Stage IV Pleural 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 ]Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
- Incidence of Adverse Events, Graded Per NCI CTCAE Version 4 [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]Grade 3 or higher AE of any type, regardless of attribution.
- Overall Survival [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]Analyzed using the Kaplan-Meier method.
- Progression-free Survival [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]Time to disease progression or death from any cause. Analyzed using the Kaplan-Meier method.
- 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|
|Study Completion Date:||March 2015|
|Primary Completion Date:||March 2015 (Final data collection date for primary outcome measure)|
Experimental: Treatment (tivantinib)
Patients receive tivantinib 360 PO BID. Treatment continues in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studiesDrug: Tivantinib
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 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, Illinois|
|Chicago, Illinois, United States, 60611|
|University of Chicago Comprehensive Cancer Center|
|Chicago, Illinois, United States, 60637|
|Decatur Memorial Hospital|
|Decatur, Illinois, United States, 62526|
|NorthShore University HealthSystem-Evanston Hospital|
|Evanston, Illinois, United States, 60201|
|Ingalls Memorial Hospital|
|Harvey, Illinois, United States, 60426|
|Peoria, Illinois, United States, 61615|
|Southern Illinois University School of Medicine|
|Springfield, Illinois, United States, 62702|
|United States, Indiana|
|Fort Wayne Medical Oncology and Hematology Inc-Parkview|
|Fort Wayne, Indiana, United States, 46845|
|Indiana University/Melvin and Bren Simon Cancer Center|
|Indianapolis, Indiana, United States, 46202|
|United States, Michigan|
|University of Michigan Comprehensive Cancer Center|
|Ann Arbor, Michigan, United States, 48109|
|Wayne State University/Karmanos Cancer Institute|
|Detroit, Michigan, United States, 48201|
|United States, Missouri|
|Mercy Hospital Saint Louis|
|Saint Louis, Missouri, United States, 63141|
|United States, Pennsylvania|
|Penn State Milton S Hershey Medical Center|
|Hershey, Pennsylvania, United States, 17033-0850|
|University of Pittsburgh Cancer Institute|
|Pittsburgh, Pennsylvania, United States, 15232|
|Principal Investigator:||Hedy Kindler||University of Chicago Comprehensive Cancer Center|