Tivantinib in Treating Patients With Previously Treated Malignant Mesothelioma
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|ClinicalTrials.gov Identifier: NCT01861301|
Recruitment Status : Terminated
First Posted : May 23, 2013
Results First Posted : October 24, 2016
Last Update Posted : October 24, 2016
|Condition or disease||Intervention/treatment||Phase|
|Epithelioid Mesothelioma Recurrent Malignant Mesothelioma Sarcomatoid Mesothelioma Stage II Pleural Mesothelioma Stage III Pleural Mesothelioma Stage IV Pleural Mesothelioma||Other: Laboratory Biomarker Analysis Drug: Tivantinib||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||18 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 2 Study of ARQ 197 in Patients With Previously-Treated Malignant Mesothelioma|
|Study Start Date :||January 2013|
|Actual Primary Completion Date :||March 2015|
|Actual Study Completion Date :||March 2015|
Experimental: Treatment (tivantinib)
Patients receive tivantinib 360 PO BID. Treatment continues in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
- 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 ]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 ]Grade 3 or higher AE of any type, regardless of attribution.
- Overall Survival [ Time Frame: Up to 2 years ]Analyzed using the Kaplan-Meier method.
- Progression-free Survival [ Time Frame: Up to 2 years ]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 ]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 ]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 ]Will be evaluated using the Cox regression model.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01861301
|Principal Investigator:||Hedy Kindler||University of Chicago Comprehensive Cancer Center|