NCT01749384

Tivantinib and Bevacizumab in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery

Phase I Study of Tivantinib Plus Bevacizumab

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects of and best dose of tivantinib when given together with bevacizumab in treating patients with solid tumors that have spread to other areas of the body or cannot be removed by surgery. Tivantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, may block tumor growth in different ways by targeting certain cells. Bevacizumab may also stop the growth of cancer by blocking blood flow to the tumor. Giving tivantinib together with bevacizumab may work better in treating tumor cells.

Detailed description

PRIMARY OBJECTIVES: I. Determine the recommended phase II dose (RP2D) of the vascular endothelial growth factor (VEGF) monoclonal antibody, bevacizumab in combination with the allosteric met proto-oncogene (MET) inhibitor, tivantinib, in patients with advanced solid tumors. SECONDARY OBJECTIVES: I. Describe the dose-limiting toxicity (DLT) and other toxicities associated with bevacizumab in combination with tivantinib as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.0. II. Document anti-tumor activity of bevacizumab in combination with tivantinib in patients with advanced solid tumors. III. Determine the pharmacokinetics of tivantinib when administered in combination with bevacizumab in patients with advanced solid tumors. IV. Perform cytochrome P450 family 2, subfamily C, polypeptide 19 (CYP2C19) genotyping on all subjects and correlate with pharmacokinetics and toxicity. V. Assess the effect of bevacizumab plus tivantinib on plasma components of the hepatocellular growth factor (HGF)-MET signaling pathway (HGF, HGF activator \[HGFA\]) and VEGF signaling pathway (VEGF A, B, C, D and placental growth factor \[PIGF\]). VI. Assess tissue (tumor and skin) protein biomarkers before and after study treatment including MET, phospho-MET\^tyrosine (Tyr)1349 and phosphor-focal adhesion kinase (FAK)\^Tyr861. VII. Assess early therapy response by quantitative biomarker imaging fludeoxyglucose F 18 (F-18 FDG) positron emission tomography (PET) and magnetic imaging resonance (MRI) on a smaller sample (n up to 15) of subjects willing to participate in the imaging assessment through UPCI 12-096. OUTLINE: This is a dose-escalation study of tivantinib. Patients receive bevacizumab intravenously (IV) over 30-90 minutes on days -15, 1, and 15 (day -15 of course 1 only) and tivantinib orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 4 weeks.

Conditions

• Solid Neoplasm

Interventions

Type	Name	Description
BIOLOGICAL	Bevacizumab	Given IV
OTHER	Laboratory Biomarker Analysis	Correlative studies
OTHER	Pharmacological Study	Correlative studies
DRUG	Tivantinib	Given PO

Timeline

• Start date: 2012-12-06
• Primary completion: 2016-05-24
• Completion: 2016-05-24
• First posted: 2012-12-13
• Last updated: 2017-10-12

Locations

2 sites across 1 country: United States