Clinical trial NCT01745367: Tivozanib in Combination With Paclitaxel in Patients With Locally Recurrent or Metastatic Triple Negative Breast Cancer
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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Triple Negative Breast Cancer
Keywords: Tivozanib hydrochloride
triple negative breast cancer
paclitaxel
pharmacokinetics
biomarkers
metastatic breast cancer
mBC
TNBC
Lead sponsor: AVEO Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Astellas Pharma Inc
First posted: 2012-12-10
Enrollment: 30
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Comparison of Progression-free Survival (PFS) of Subjects
timeFrame: approximately 24 months
Secondary outcomes:
measure: Comparison of Objective Response Rate (ORR) and Duration of Response (DoR) of Subjects
timeFrame: approximately 24 months
measure: Comparison of Overall Survival (OS) of Subjects
timeFrame: approximately 24 months
measure: Safety and Tolerability of Tivozanib Hydrochloride in Combination With Paclitaxel vs Placebo in Combination With Paclitaxel
timeFrame: approximately 24 months
measure: Pharmacokinetics (PK) of Tivozanib Hydrochloride and Paclitaxel When Administered in Combination
timeFrame: approximately 24 months
measure: Identification of Hypoxia Gene Signature
timeFrame: 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
measure: Measurement of Subjects' Quality of Life (QoL)
timeFrame: approximately 24 months
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Jacksonville
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Oak Lawn
country: United States
state: Illinois
city: Fort Wayne
country: United States
state: Indiana
city: Indianapolis
country: United States
state: Indiana
city: Baltimore
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Saint Louis
country: United States
state: Missouri
city: Bronx
country: United States
state: New York
city: New York
country: United States
state: New York
city: Chapel Hill
country: United States
state: North Carolina
city: Fargo
country: United States
state: North Dakota
city: Charleston
country: United States
state: South Carolina
city: Sioux Falls
country: United States
state: South Dakota
city: Memphis
country: United States
state: Tennessee
city: Dallas
country: United States
state: Texas
city: Galveston
country: United States
state: Texas
city: Port Macquarie
country: Australia
state: New South Wales
city: Woodville South
country: Australia
state: South Australia
city: Bentleigh
country: Australia
state: Victoria
city: Newcastle
country: Australia
city: South Brisbane
country: Australia
city: St Leonards
country: Australia
city: Nassau
country: Bahamas
city: Calgary
country: Canada
state: Alberta
city: Edmonton
country: Canada
state: Alberta
city: Vancouver
country: Canada
state: British Columbia
city: Toronto
country: Canada
state: Ontario
city: Saint John
country: Canada
city: Berlin
country: Germany
city: Cologne
country: Germany
city: Hanau am Main
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
Study officials:
affiliation: AVEO Pharmaceuticals, Inc.
name: Michael Needle
role: STUDY_CHAIR
References: