Tivozanib in Combination With Paclitaxel in Patients With Locally Recurrent or Metastatic Triple Negative Breast Cancer
- Conditions
- Triple Negative Breast Cancer
- Interventions
- Registration Number
- NCT01745367
- Lead Sponsor
- AVEO Pharmaceuticals, Inc.
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- Female
- Target Recruitment
- 30
- 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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo in combination with paclitaxel 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). Placebo in combination with paclitaxel Placebo 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). Tivo in combination with paclitaxel Tivozanib Hydrochloride 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). Tivo in combination with paclitaxel 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).
- Primary Outcome Measures
Name Time Method Comparison of Progression-free Survival (PFS) of Subjects 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 Outcome Measures
Name Time Method Comparison of Objective Response Rate (ORR) and Duration of Response (DoR) of Subjects approximately 24 months ORR is defined as the proportion of patients with tumor size reduction of a predefined amount and for a minimum time period. DoR is defined as the length of time that a tumor continues to respond to treatment without the cancer growing or spreading. The ORR and DoR comparison was performed for subjects treated with tivozanib hydrochloride in combination with paclitaxel vs placebo in combination with paclitaxel.
Comparison of Overall Survival (OS) of Subjects approximately 24 months OS measures how long subjects, who undergo a certain treatment regimen, live compared to subjects who are in a control group (i.e., taking either another drug or an inactive treatment, known as a placebo). OS comparison was performed for subjects treated with tivozanib hydrochloride in combination with paclitaxel vs placebo in combination with paclitaxel.
Safety and Tolerability of Tivozanib Hydrochloride in Combination With Paclitaxel vs Placebo in Combination With Paclitaxel approximately 24 months Number of subjects with serious and non-serious adverse events.
Pharmacokinetics (PK) of Tivozanib Hydrochloride and Paclitaxel When Administered in Combination approximately 24 months PK is defined as the study of the bodily absorption, distribution, metabolism, and excretion of drugs.
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 Evaluation of hypoxia gene signature as a predictive biomarker of tivozanib hydrochloride response and establish the optimal cut-off to identify biomarker positive and negative subgroups. The genes comprising the hypoxia gene signature was analyzed in tumor tissue from subjects.
Measurement of Subjects' Quality of Life (QoL) approximately 24 months The Functional Assessment of Cancer Therapy-Breast (FACT-B) and Euro Quality of Life - 5 Dimensions (EQ-5D) questionnaires was used throughout the study to measure subjects' health-related QoL.