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
Overview
- Phase
- Phase 2
- Intervention
- paclitaxel
- Conditions
- Triple Negative Breast Cancer
- Sponsor
- AVEO Pharmaceuticals, Inc.
- Enrollment
- 30
- Primary Endpoint
- Comparison of Progression-free Survival (PFS) of Subjects
- Status
- Terminated
- Last Updated
- 5 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
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
Arms & Interventions
Placebo in combination with paclitaxel
Placebo orally once daily on a 3 weeks on/1 week off schedule with 90 mg/m2 of paclitaxel administered intravenously 3 weeks on (Day 1, Day 8 and Day 15)/1 week off (4 weeks = 1 Cycle).
Intervention: paclitaxel
Placebo in combination with paclitaxel
Placebo orally once daily on a 3 weeks on/1 week off schedule with 90 mg/m2 of paclitaxel administered intravenously 3 weeks on (Day 1, Day 8 and Day 15)/1 week off (4 weeks = 1 Cycle).
Intervention: Placebo
Tivo in combination with paclitaxel
1.5 mg tivozanib hydrochloride orally once daily on a 3 weeks on/1 week off schedule with 90 mg/m2 of paclitaxel administered intravenously 3 weeks on (Day 1, Day 8 and Day 15)/1 week off (4 weeks = 1 Cycle).
Intervention: Tivozanib Hydrochloride
Tivo in combination with paclitaxel
1.5 mg tivozanib hydrochloride orally once daily on a 3 weeks on/1 week off schedule with 90 mg/m2 of paclitaxel administered intravenously 3 weeks on (Day 1, Day 8 and Day 15)/1 week off (4 weeks = 1 Cycle).
Intervention: paclitaxel
Outcomes
Primary Outcomes
Comparison of Progression-free Survival (PFS) of Subjects
Time Frame: approximately 24 months
PFS is defined as the time from randomization to progressive disease (PD) or death. The PFS comparison was performed for subjects treated with tivozanib hydrochloride in combination with paclitaxel vs placebo in combination with paclitaxel.
Secondary Outcomes
- Comparison of Objective Response Rate (ORR) and Duration of Response (DoR) of Subjects(approximately 24 months)
- Comparison of Overall Survival (OS) of Subjects(approximately 24 months)
- Safety and Tolerability of Tivozanib Hydrochloride in Combination With Paclitaxel vs Placebo in Combination With Paclitaxel(approximately 24 months)
- Pharmacokinetics (PK) of Tivozanib Hydrochloride and Paclitaxel When Administered in Combination(approximately 24 months)
- Identification of Hypoxia Gene Signature(Cycle 1, Day 1: Pre-dose and 2, 4 and 24 hours post dose; Cycle 1, Day 8: Pre-dose; Cycle 1, Day 21: Pre-dose and 2, 4, 24, 48, and 96 hours post dose; Cycle 2 (Day 1): Pre-dose)
- Measurement of Subjects' Quality of Life (QoL)(approximately 24 months)