This phase II trial studies how well tivantinib works in treating patients with recurrent or metastatic breast cancer. Tivantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PRIMARY OBJECTIVES: I. To evaluate the activity of tivantinib (ARQ-197) as defined by 6-month progression-free survival (PFS) of participants with triple-negative metastatic breast cancer. SECONDARY OBJECTIVES: I. To evaluate objective response based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. II. To evaluate c-Met and phospho c-Met expression in archival tumor tissue. (Exploratory) III. To evaluate the incidence of c-Met-positive circulating tumor cells at baseline. (Exploratory) IV. To evaluate the effect of ARQ-197 on serum markers relevant to c-Met pathway (hepatocyte growth factor \[HGF\] and vascular endothelial growth factor \[VEGF\]). (Exploratory) V. To evaluate phosphatase and tensin homolog (PTEN) loss and PI3K mutations in archival tumor tissue. (Exploratory) VI. To evaluate proportion of participants with basal-like breast cancer. (Exploratory) OUTLINE: This is a multicenter study. Patients receive tivantinib orally (PO) twice daily (BID) on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection at baseline and periodically during study for c-Met expression, relevant markers (HGF and VEGF), PTEN loss, and PI3K mutation analysis by fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC). Archived tumor tissue samples are also analyzed. After completion of study treatment, patients are followed up every 6 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
22
Correlative studies
Given PO
Dana-Farber Cancer Institute Faulkner Hospital
Boston, Massachusetts, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
PFS Status
Analyzed using the Kaplan-Meier method. 95% confidence intervals (CI) will be determined. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time frame: Time from start of treatment to time of progression or death, assessed up to 6 months
Overall Response Using RECIST v1.1
The 95% confidence intervals should be provided. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by Conventional 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.
Time frame: Up to 1 year
To Evaluate c-Met Expression in Archival Tumor Tissue.
Assessment of ploidy status was done by visual screening of all tumor area; cells with maximum number of signals were recorded. MET amplification was defined as a MET/CEP7 ratio ≥ 2. Samples having a MET/CEP7 ratio from 1.5 and up to 2 were defined as having relative MET gain. Samples with a MET/CEP7 ratio of 1 but with more than two copies of each probe were defined as having polysomy of chromosome 7.
Time frame: Baseline
To Evaluate Phospho c-Met Expression in Archival Tumor Tissue.
MET amplification was defined as a MET/CEP7 ratio ≥ 2. Samples having a MET/CEP7 ratio from 1.5 and up to 2 were defined as having relative MET gain. Samples with a MET/CEP7 ratio of 1 but with more than two copies of each probe were defined as having polysomy of chromosome 7.
Time frame: Baseline
To Evaluate the Incidence of c-Met Positive Circulating Tumor Cells.
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Time frame: Baseline