Tivozanib in Combination With Paclitaxel in Patients With Locally Recurrent or Metastatic Triple Negative Breast Cancer (BATON-BC)

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.

Study Overview

• Status: Terminated
• Conditions: Triple Negative Breast Cancer
• Intervention / Treatment: Drug: Placebo; Drug: paclitaxel; Drug: Tivozanib Hydrochloride

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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Newcastle, Australia
  • South Brisbane, Australia
  • St Leonards, Australia
  • New South Wales
    • Port Macquarie, New South Wales, Australia
  • South Australia
    • Woodville South, South Australia, Australia
  • Victoria
    • Bentleigh, Victoria, Australia, 3204
• Bahamas
  • Nassau, Bahamas
• Canada
  • Saint John, Canada
  • Alberta
    • Calgary, Alberta, Canada
    • Edmonton, Alberta, Canada
  • British Columbia
    • Vancouver, British Columbia, Canada
  • Ontario
    • Toronto, Ontario, Canada
• Germany
  • Berlin, Germany
  • Cologne, Germany
  • Hanau am Main, Germany, 63454
  • Leipzig, Germany
  • Muenster, Germany
  • Tuebingen, Germany
• Italy
  • Avellino, Italy
  • Milano, Italy
  • Roma, Italy
  • Torino, Italy
  • Viterbo, Italy
• Korea, Republic of
  • Seoul, Korea, Republic of
• Spain
  • Barcelona, Spain
  • Madrid, Spain
  • Malaga, Spain
  • Sevilla, Spain
• Taiwan
  • Kaohsiung, Taiwan
  • Taipei, Taiwan
• Ukraine
  • Dnipropetrovsk, Ukraine
  • Donetsk, Ukraine
  • Uzhhorod, Ukraine
  • Vinnytsia, Ukraine
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35005
  • Florida
    • Jacksonville, Florida, United States, 32034
    • Miami, Florida, United States, 33018
  • Georgia
    • Atlanta, Georgia, United States, 30301
  • Illinois
    • Chicago, Illinois, United States, 60007
    • Oak Lawn, Illinois, United States, 60456
  • Indiana
    • Fort Wayne, Indiana, United States, 46774
    • Indianapolis, Indiana, United States, 46077
  • Maryland
    • Baltimore, Maryland, United States, 21201
  • Massachusetts
    • Boston, Massachusetts, United States, 01841
  • Missouri
    • Saint Louis, Missouri, United States, 63101
  • New York
    • Bronx, New York, United States, 10453
    • New York, New York, United States, 10001
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
  • North Dakota
    • Fargo, North Dakota, United States, 58102
  • South Carolina
    • Charleston, South Carolina, United States, 02129
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57101
  • Tennessee
    • Memphis, Tennessee, United States, 37501
  • Texas
    • Dallas, Texas, United States, 75001
    • Galveston, Texas, United States, 77550

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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).	Drug: Placebo; Drug: paclitaxel; Other Names: PTX
Experimental: 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).	Drug: paclitaxel; Other Names: PTX; Drug: Tivozanib Hydrochloride; Other Names: Tivozanib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: AVEO Pharmaceuticals, Inc.
• Collaborators: Astellas Pharma Inc
• Investigators: Study Chair: Michael Needle, AVEO Pharmaceuticals, Inc.

Publications and helpful links

Helpful Links

• Aveo Pharmaceuticals, Inc. official web page

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: December 6, 2012
• First Submitted That Met QC Criteria: December 7, 2012
• First Posted (Estimate): December 10, 2012

Study Record Updates

• Last Update Posted (Actual): October 27, 2020
• Last Update Submitted That Met QC Criteria: October 5, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: biomarkers; paclitaxel; pharmacokinetics; TNBC; metastatic breast cancer; triple negative breast cancer; mBC; Tivozanib hydrochloride
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel
• Other Study ID Numbers: AV-951-12-204; 2012-003507-35 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO