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
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 30
- 主要终点
- Comparison of Progression-free Survival (PFS) of Subjects
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
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).
干预措施: paclitaxel (Drug)
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).
干预措施: Placebo (Drug)
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).
干预措施: Tivozanib Hydrochloride (Drug)
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).
干预措施: paclitaxel (Drug)
结局指标
主要结局
Comparison of Progression-free Survival (PFS) of Subjects
时间窗: 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.
次要结局
- 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)