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

Triple Negative Breast Cancer Clinical Trial

— BATON-BC  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01745367
• Other study ID #: AV-951-12-204
• Secondary ID: 2012-003507-35
• Status: Terminated
• Phase: Phase 2
• Start date: November 2012
• Est. completion date: June 2014

Study information

• Verified date: October 2020
• Source: AVEO Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 30
• Est. completion date: June 2014
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

Drug:
• Tivozanib Hydrochloride

• paclitaxel

• Placebo

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
AVEO Pharmaceuticals, Inc.	Astellas Pharma Inc

Countries where clinical trial is conducted

United States,  Australia,  Bahamas,  Canada,  Germany,  Italy,  Korea, Republic of,  Spain,  Taiwan,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Comparison of Progression-free Survival (PFS) of Subjects	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.	approximately 24 months
Secondary	Comparison of Objective Response Rate (ORR) and Duration of Response (DoR) of Subjects	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.	approximately 24 months
Secondary	Comparison of Overall Survival (OS) of Subjects	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.	approximately 24 months
Secondary	Safety and Tolerability of Tivozanib Hydrochloride in Combination With Paclitaxel vs Placebo in Combination With Paclitaxel	Number of subjects with serious and non-serious adverse events.	approximately 24 months
Secondary	Pharmacokinetics (PK) of Tivozanib Hydrochloride and Paclitaxel When Administered in Combination	PK is defined as the study of the bodily absorption, distribution, metabolism, and excretion of drugs.	approximately 24 months
Secondary	Identification of Hypoxia Gene Signature	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.	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
Secondary	Measurement of Subjects' Quality of Life (QoL)	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.	approximately 24 months

External Links

•   Aveo Pharmaceuticals, Inc. official web page