Tivantinib in Treating Patients With Recurrent or Metastatic Breast Cancer

NCT01575522 | Completed Phase 2 Results

• 7 other identifiers: NCI-2012-00722DFCI-12-017CDR000073010212-0178985P30CA006516U01CA062490
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Estrogen Receptor Negative; HER2/Neu Negative; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Stage IV Breast Cancer; Triple-Negative Breast Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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 from start of treatment to time of progression or death, assessed up to 6 months

Secondary Outcomes (4)

• Overall Response Using RECIST v1.1

  Up to 1 year

• To Evaluate c-Met Expression in Archival Tumor Tissue.

  Baseline

• To Evaluate Phospho c-Met Expression in Archival Tumor Tissue.

  Baseline

• To Evaluate the Incidence of c-Met Positive Circulating Tumor Cells.

  Baseline

Study Arms (1)

Treatment (tivantinib)

EXPERIMENTAL

Patients receive tivantinib 360 mg PO 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 FISH and IHC. Archived tumor tissue samples are also analyzed.

Other: Laboratory Biomarker Analysis; Drug: Tivantinib

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (tivantinib)

Tivantinib DRUG

Given PO

Also known as: ARQ 197, ARQ-197, c-Met Inhibitor ARQ 197

Treatment (tivantinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have histologically or cytologically confirmed invasive breast cancer, with recurrent or metastatic disease; participants without pathologic or cytologic confirmation of metastatic disease should have unequivocal evidence of metastasis from physical examination or radiologic evaluation
• Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>= 20 mm with conventional techniques or as \>= 10 mm with spiral computed tomography (CT) scan
• Participants must have recent evidence of progressive disease
• Participants must have received 1-3 prior chemotherapeutic regimens for metastatic breast cancer and must have been off treatment with chemotherapy for at least 14 days before enrollment in the study
• Participants must have discontinued all biologic therapy (including vaccines) at least 14 days before enrollment in the study
• Participants must have discontinued any investigational therapy at least 14 days before enrollment in the study
• Participants may have received prior radiation therapy in either the metastatic or early-stage setting
• Radiation therapy must be completed at least 14 days before enrollment in the study
• Participant must not have received radiation to \> 25% of his or her bone marrow within 30 days of starting study treatment
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
• Hemoglobin \>= 9.0 g/dL
• Absolute neutrophil count \>= 1,500/mcL
• Platelets \>= 100,000/mcL
• Total bilirubin =\< 1.5 times upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase \[SGPT\]) =\< 2.5 times institutional ULN; for participants with documented liver metastases, AST/ALT =\< 5.0 times ULN

You may not qualify if:

• Participants who have received chemotherapy, biologic, investigational, or radiotherapy within 14 days prior to entering the study
• Participants who are receiving any other investigational agents
• Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms
• Participants with a history of treated central nervous system (CNS) metastases are eligible
• Treated brain metastases are defined as those having no evidence of progression or hemorrhage for \>= 2 months after treatment, and no ongoing requirement for corticosteroids, as ascertained by clinical examination and brain imaging (magnetic resonance imaging or computed tomography \[CT\] scan) during the screening period
• Treatment for brain metastases may include whole-brain radiotherapy, radiosurgery, or a combination as deemed appropriate by the treating physician
• Participants may be taking anti-convulsant medications, which must be non-enzyme-inducing anti-epileptic drugs
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ARQ 197
• History of congestive heart failure defined as Class II to IV per New York Heart Association (NYHA) classification; active coronary artery disease (CAD); clinically significant bradycardia or other uncontrolled, cardiac arrhythmia defined as \>= grade 3 according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, or uncontrolled hypertension; myocardial infarction occurring within 6 months prior to study entry (myocardial infarction occurring \> 6 months prior to study entry is permitted)
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study
• Human immunodeficiency virus (HIV)-positive participants on combination antiretroviral therapy are ineligible

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

Dana-Farber Cancer Institute Faulkner Hospital

Boston, Massachusetts, 02130, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• Tolaney SM, Tan S, Guo H, Barry W, Van Allen E, Wagle N, Brock J, Larrabee K, Paweletz C, Ivanova E, Janne P, Overmoyer B, Wright JJ, Shapiro GI, Winer EP, Krop IE. Phase II study of tivantinib (ARQ 197) in patients with metastatic triple-negative breast cancer. Invest New Drugs. 2015 Oct;33(5):1108-14. doi: 10.1007/s10637-015-0269-8. Epub 2015 Jul 1.

  PMID: 26123926 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

ARQ 197

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Sara M. Tolaney, MD, MPH
• Organization: Dana-Farber Cancer Institute

Sara_Tolaney@dfci.harvard.edu

617.632.5743

Study Officials

• Sara Tolaney

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2012
• First Posted: April 11, 2012
• Study Start: March 1, 2012
• Primary Completion: July 1, 2013
• Study Completion: July 1, 2013
• Last Updated: March 21, 2016
• Results First Posted: March 21, 2016

Record last verified: 2015-10

Locations

US (2)