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

NCT01745367 | Terminated Phase 2 Results DMC

• 2 other identifiers: AV-951-12-2042012-003507-35
• Study Type: interventional
• Target: 30
• Locations: 10 countries
• Sites: 54

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.

Conditions

Triple Negative Breast Cancer

Keywords

Tivozanib hydrochloride; triple negative breast cancer; paclitaxel; pharmacokinetics; biomarkers; metastatic breast cancer; mBC; TNBC

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• 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

Study Arms (2)

Placebo in combination with paclitaxel

ACTIVE COMPARATOR

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: paclitaxel; Drug: Placebo

Tivo in combination with paclitaxel

EXPERIMENTAL

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: Tivozanib Hydrochloride; Drug: paclitaxel

Interventions

Tivozanib Hydrochloride DRUG

Also known as: Tivozanib

Tivo in combination with paclitaxel

paclitaxel DRUG

Also known as: PTX

Placebo in combination with paclitaxel; Tivo in combination with paclitaxel

Placebo DRUG

Placebo in combination with paclitaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• AVEO Pharmaceuticals, Inc.: lead
• Astellas Pharma Inc: collaborator

Study Sites (54)

Unknown Facility

Birmingham, Alabama, 35005, United States

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Jacksonville, Florida, 32034, United States

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Miami, Florida, 33018, United States

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Atlanta, Georgia, 30301, United States

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Chicago, Illinois, 60007, United States

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Oak Lawn, Illinois, 60456, United States

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Fort Wayne, Indiana, 46774, United States

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Indianapolis, Indiana, 46077, United States

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Baltimore, Maryland, 21201, United States

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Boston, Massachusetts, 01841, United States

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St Louis, Missouri, 63101, United States

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New York, New York, 10001, United States

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The Bronx, New York, 10453, United States

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Chapel Hill, North Carolina, 27514, United States

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Fargo, North Dakota, 58102, United States

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Charleston, South Carolina, 02129, United States

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Sioux Falls, South Dakota, 57101, United States

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Memphis, Tennessee, 37501, United States

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Dallas, Texas, 75001, United States

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Galveston, Texas, 77550, United States

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Port Macquarie, New South Wales, Australia

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Woodville South, South Australia, Australia

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Bentleigh, Victoria, 3204, Australia

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Newcastle, Australia

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South Brisbane, Australia

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St Leonards, Australia

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Calgary, Alberta, Canada

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Edmonton, Alberta, Canada

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Vancouver, British Columbia, Canada

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Toronto, Ontario, Canada

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Saint John, Canada

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Berlin, Germany

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Cologne, Germany

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Hanau, 63454, Germany

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Leipzig, Germany

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Münster, Germany

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Tübingen, Germany

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Avellino, Italy

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Milan, Italy

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Roma, Italy

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Torino, Italy

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Viterbo, Italy

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Seoul, South Korea

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Barcelona, Spain

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Madrid, Spain

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Málaga, Spain

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Seville, Spain

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Kaohsiung City, Taiwan

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Taipei, Taiwan

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Nassau, The Bahamas

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Dnipropetrovsk, Ukraine

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Donetsk, Ukraine

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Uzhhorod, Ukraine

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Vinnytsia, Ukraine

Location

Related Links

• Aveo Pharmaceuticals, Inc. official web page

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Breast Neoplasms

Interventions

tivozanib; Paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Limitations and Caveats

The Sponsor terminated Study AV-951-12-204 before enrollment was completed after determining that enrollment of subjects was much lower than expected, and that timely completion of the study was not feasible.

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Aveo Pharmaceuticals, Inc.

Clinical@aveooncology.com

857-400-0101

Study Officials

• Michael Needle

  AVEO Pharmaceuticals, Inc.

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2012
• First Posted: December 10, 2012
• Study Start: November 1, 2012
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2014
• Last Updated: October 27, 2020
• Results First Posted: October 27, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

ES (4); AU (6); UA (4); US (20); CA (5); DE (6); TW (2); KR (1); TH (1); IT (5)