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Capecitabine

Tivozanib

Antimetabolites

Protein Kinase Inhibitors

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Tivozanib 1.0 mg or 1.5 mg oral once daily for 2 weeks followed by 1 week off. Capecitabine 825 mg/m2, 1000 mg/m2, or 1250 mg/m2, oral twice daily for 2 weeks followed by 1 week off. 1 cycle= 3 weeks. Cycles will be repeated in the absence of disease progression or unacceptable toxicity.

tivozanib (AV-951) and capecitabine (Xeloda®)

Shefali Agarwal, M.D.

This is an open-label, multi-center, dose-finding study of tivozanib administered in combination with capecitabine. During the dose-escalation portion, sequential cohorts of subjects with advanced solid tumors will be enrolled in order to establish the maximum tolerated dose (MTD). If the MTD is not reached, the recommended Phase 2 dose (RP2D) will be determined. In the expansion cohort, subjects with locally advanced or metastatic breast or colon cancer will be enrolled at MTD (or RP2D) to further evaluate safety and activity of this combination in these tumor types.

This is a Phase Ib, open-label, multi-center, dose-escalation study of orally administered tivozanib in combination with capecitabine to approximately 24 subjects with advanced solid tumors and, in the expanded MTD cohort, subjects with locally advanced or metastatic breast or colorectal cancer. This study is designed to evaluate the safety, tolerability, dose-limiting toxicities, maximum tolerated dose, pharmacokinetic, and antineoplastic activity. The number of cohorts evaluated and the maximum doses to be administered will depend upon the observed tolerability. Dose level "0", tivozanib HCl 1.5 mg and capecitabine 1000 mg/m² BID, is the starting dose level. Once assigned to a cohort, each subject will continue to be treated at the same dose level and schedule throughout the course of the study.

A Trial of Tivozanib (AV-951) in Combination With Capecitabine (Xeloda®) in Subjects With Advanced Solid Tumors

A Phase 1b, Open-Label, Dose-Escalating Trial of Tivozanib (AV-951) in Combination With Capecitabine (Xeloda®) in Subjects With Advanced Solid Tumors

Assessment of any dose-limiting toxcities

PK parameters of tivozanib and capecitabine will be calculated from serum and plasma levels. These will be summarized descriptively and presented by visit and dose cohort. PK parameters will be calculated using non compartmental and/or compartmental models and PK parameters will be summarized and presented. The mean (± STDEM) concentration-time profiles of tivozanib, capecitabine, and their metabolite(s) will be presented for each dose.

Disease and response assessments will be determined using Response Evaluation Criteria in Solid Tumors (RECIST Version 1.0). Disease assessment is to include disease classification, tumor marker assessments, and diagnostic imaging / measurement of marker lesions. Computerized tomography (CT) will be considered the standard method for evaluating disease status. All subjects should have a CT scan (or MRI) of the head, chest, abdomen, and pelvis at baseline. The location and dimensions of "marker" lesions will be documented.

Spots Global Cancer Trial Database for locally advanced or metastatic breast or colorectal cancer