Tivozanib in Combination With Paclitaxel in Patients With Locally Recurrent or Metastatic Triple Negative Breast Cancer

A Phase 2 Randomized, Double-Blind, Placebo-Controlled, Study Comparing Tivozanib Hydrochloride in Combination With Paclitaxel v Placebo in Combination With Paclitaxel in Locally Recurrent and/or Metastatic Triple Negative Breast Cancer

This is a phase 2 multicenter, double-blind, randomized, placebo-controlled, two-arm study for subjects with locally recurrent or metastatic triple negative breast cancer.

This is a phase 2 multicenter, double-blind, randomized, placebo-controlled, two-arm study for subjects with locally recurrent or metastatic triple negative breast cancer.

Patients will be randomized 2:1 to either tivozanib hydrochloride and weekly paclitaxel or placebo and weekly paclitaxel.

Subjects will be stratified based on Eastern Cooperative Oncology Group (ECOG) performance score (0 vs 1) and line of treatment (first vs second).

All subjects will be evaluated for progression free survival and overall survival as well as safety and tolerability. Biomarker and pharmacokinetic (PK) analysis are also included in study. This study will determine whether tivozanib hydrocholoride combined with weekly paclitaxel improves clinical outcomes in patients with triple negative breast cancer.

Inclusion Criteria:

• Locally recurrent or metastatic TNBC, defined as ER/PR <1%, HER2 0-1+, or 2+ with negative FISH
• Measurable disease per RECIST version 1.1
• ECOG performance status of 0 or 1
• Confirmed available archival tumor tissue.

Exclusion Criteria:

• More than 1 prior systemic chemotherapy for treatment of locally recurrent or metastatic breast cancer (neoadjuvant and adjuvant therapy is allowed provided the subject did not progress within 12 months of taxane based therapy
• Prior treatment with VEGF pathway targeted agent
• Major surgery within 4 weeks or minor surgery or radiotherapy within 2 weeks of first dose of study drug
• Known history of central nervous system metastasis (subjects with previously treated (radiotherapy or surgery) brain metastasis that have been stable off steroids or enzyme-inducing antiepileptic drugs for at least 3 months following prior treatment may be enrolled)
• Significant hematologic, gastrointestinal, thromboembolic, vascular, bleeding, or coagulation disorders
• Significant serum chemistry or urinalysis abnormalities
• Significant cardiovascular disease, including: uncontrolled hypertension; myocardial infarction or unstable angina within 6 months prior to administration of first dose of study drug; and symptomatic left ventricular dysfunction or baseline left ventricular ejection fraction (LVEF) by multigated acquisition scan (MUGA) or ECHO.
• Severe peripheral neuropathy ≥ Grade 2
• Currently active second primary malignancy