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

Primary Purpose

Triple Negative Breast Cancer

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Tivozanib Hydrochloride
paclitaxel
Placebo
Sponsored by
AVEO Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Triple Negative Breast Cancer focused on measuring Tivozanib hydrochloride, triple negative breast cancer, paclitaxel, pharmacokinetics, biomarkers, metastatic breast cancer, mBC, TNBC

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Placebo in combination with paclitaxel

Tivo in combination with paclitaxel

Arm Description

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).

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).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.

Full Information

First Posted
December 6, 2012
Last Updated
October 5, 2020
Sponsor
AVEO Pharmaceuticals, Inc.
Collaborators
Astellas Pharma Inc
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1. Study Identification

Unique Protocol Identification Number
NCT01745367
Brief Title
Tivozanib in Combination With Paclitaxel in Patients With Locally Recurrent or Metastatic Triple Negative Breast Cancer
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2020
Overall Recruitment Status
Terminated
Why Stopped
low enrollment
Study Start Date
November 2012 (undefined)
Primary Completion Date
June 2014 (Actual)
Study Completion Date
June 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AVEO Pharmaceuticals, Inc.
Collaborators
Astellas Pharma Inc

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Triple Negative Breast Cancer
Keywords
Tivozanib hydrochloride, triple negative breast cancer, paclitaxel, pharmacokinetics, biomarkers, metastatic breast cancer, mBC, TNBC

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo in combination with paclitaxel
Arm Type
Active Comparator
Arm Description
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).
Arm Title
Tivo in combination with paclitaxel
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
Tivozanib Hydrochloride
Other Intervention Name(s)
Tivozanib
Intervention Type
Drug
Intervention Name(s)
paclitaxel
Other Intervention Name(s)
PTX
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Comparison of Progression-free Survival (PFS) of Subjects
Description
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.
Time Frame
approximately 24 months
Secondary Outcome Measure Information:
Title
Comparison of Objective Response Rate (ORR) and Duration of Response (DoR) of Subjects
Description
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.
Time Frame
approximately 24 months
Title
Comparison of Overall Survival (OS) of Subjects
Description
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.
Time Frame
approximately 24 months
Title
Safety and Tolerability of Tivozanib Hydrochloride in Combination With Paclitaxel vs Placebo in Combination With Paclitaxel
Description
Number of subjects with serious and non-serious adverse events.
Time Frame
approximately 24 months
Title
Pharmacokinetics (PK) of Tivozanib Hydrochloride and Paclitaxel When Administered in Combination
Description
PK is defined as the study of the bodily absorption, distribution, metabolism, and excretion of drugs.
Time Frame
approximately 24 months
Title
Identification of Hypoxia Gene Signature
Description
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.
Time Frame
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
Title
Measurement of Subjects' Quality of Life (QoL)
Description
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.
Time Frame
approximately 24 months

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Needle
Organizational Affiliation
AVEO Pharmaceuticals, Inc.
Official's Role
Study Chair
Facility Information:
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35005
Country
United States
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32034
Country
United States
City
Miami
State/Province
Florida
ZIP/Postal Code
33018
Country
United States
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30301
Country
United States
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60007
Country
United States
City
Oak Lawn
State/Province
Illinois
ZIP/Postal Code
60456
Country
United States
City
Fort Wayne
State/Province
Indiana
ZIP/Postal Code
46774
Country
United States
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46077
Country
United States
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
01841
Country
United States
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63101
Country
United States
City
Bronx
State/Province
New York
ZIP/Postal Code
10453
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10001
Country
United States
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27514
Country
United States
City
Fargo
State/Province
North Dakota
ZIP/Postal Code
58102
Country
United States
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
02129
Country
United States
City
Sioux Falls
State/Province
South Dakota
ZIP/Postal Code
57101
Country
United States
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
37501
Country
United States
City
Dallas
State/Province
Texas
ZIP/Postal Code
75001
Country
United States
City
Galveston
State/Province
Texas
ZIP/Postal Code
77550
Country
United States
City
Port Macquarie
State/Province
New South Wales
Country
Australia
City
Woodville South
State/Province
South Australia
Country
Australia
City
Bentleigh
State/Province
Victoria
ZIP/Postal Code
3204
Country
Australia
City
Newcastle
Country
Australia
City
South Brisbane
Country
Australia
City
St Leonards
Country
Australia
City
Nassau
Country
Bahamas
City
Calgary
State/Province
Alberta
Country
Canada
City
Edmonton
State/Province
Alberta
Country
Canada
City
Vancouver
State/Province
British Columbia
Country
Canada
City
Toronto
State/Province
Ontario
Country
Canada
City
Saint John
Country
Canada
City
Berlin
Country
Germany
City
Cologne
Country
Germany
City
Hanau am Main
ZIP/Postal Code
63454
Country
Germany
City
Leipzig
Country
Germany
City
Muenster
Country
Germany
City
Tuebingen
Country
Germany
City
Avellino
Country
Italy
City
Milano
Country
Italy
City
Roma
Country
Italy
City
Torino
Country
Italy
City
Viterbo
Country
Italy
City
Seoul
Country
Korea, Republic of
City
Barcelona
Country
Spain
City
Madrid
Country
Spain
City
Malaga
Country
Spain
City
Sevilla
Country
Spain
City
Kaohsiung
Country
Taiwan
City
Taipei
Country
Taiwan
City
Dnipropetrovsk
Country
Ukraine
City
Donetsk
Country
Ukraine
City
Uzhhorod
Country
Ukraine
City
Vinnytsia
Country
Ukraine

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
http://aveooncology.com
Description
Aveo Pharmaceuticals, Inc. official web page

Learn more about this trial

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

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