Neoadjuvant TAC Plus or Minus Bevacizumab(AVF3299)

October 9, 2015 updated by: Translational Oncology Research International

A Multicenter, Placebo-Controlled, Double-Blind Randomized Phase II Trial of Neoadjuvant Treatment With Single-Agent Bevacizumab or Placebo, Followed by Six Cycles of Docetaxel, Doxorubicin, and Cyclophosphamide (TAC), With or Without Bevacizumab in Patients With Stage II or Stage III Breast Cancer

The purpose of this study is to evaluate the safety of the TAC-bevacizumab combination and investigate whether changes in gene expression, or the expression of specific biomarkers, are either predictive of response to bevacizumab or indicative of response.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The study combines bevacizumab with a very efficacious combination chemotherapy regimen for the treatment of stage II or stage III primary breast cancer. Safety of the TAC-bevacizumab combination will be evaluated. In addition, the study design incorporates an initial cycle of bevacizumab or placebo alone. Assessing the isolated effects of bevacizumab in a setting where pre- and post-treatment tissue specimens can be obtained will provide essential information about the mechanisms by which VEGF inhibition affects tumor growth, and represents an ideal opportunity to evaluate the molecular effects of bevacizumab on breast tumor tissue.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
6

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 1Z2
        • Cross Cancer Institute
    • Quebec
      • Montreal, Quebec, Canada, H2W 1S6
        • McGill University
  • Ireland
      • Dublin, Ireland, 4
        • St. Vincent'S University Hospital
      • Dublin, Ireland, 8
        • St. James's Hospital
  • United States
    • California
      • Los Angeles, California, United States, 90095
        • UCLA Medical Center
      • Pomona, California, United States, 91767
        • Wilshire Oncology Medical Group, Inc.
    • Florida
      • Orlando, Florida, United States, 32804
        • Cancer Institute of Florida, P.A.
    • Georgia
      • Marietta, Georgia, United States, 30060
        • Northwest Georgia Oncology Centers, P.C.
    • Texas
      • San Antonio, Texas, United States, 78207
        • South Texas Oncology and Hematology, P.A.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Histologically or cytologically proven adenocarcinoma of the breast
  • Stage II (T > 3 cm) or Stage III disease (except inflammatory breast cancer), according to the AJCC Staging Manual, 6th Edition, 2002
  • HER2-negative disease (as defined by fluorescence in situ hybridization [FISH])
  • ECOG performance status 0-1
  • No prior chemotherapy, radiotherapy, or endocrine therapy for invasive or noninvasive breast cancer
  • Normal cardiac function (ejection fraction > lower limit of normal) as determined by MUGA or echocardiogram
  • Adequate organ function

Exclusion Criteria:

  • Prior chemotherapy or radiotherapy for Stage II or Stage III breast cancer
  • Inflammatory Breast Cancer, clinically defined as the presence of erythema or induration involving one-third or more of the breast
  • Prior treatment with an anti-angiogenic agent
  • Prior ipsilateral radiation therapy for invasive or non-invasive breast cancer
  • Bilateral invasive breast cancer
  • Concurrent therapy with any other non-protocol anti-cancer therapy
  • Current therapy with hormone replacement therapy, or any hormonal agent such as raloxifene, tamoxifen, or other selective estrogen receptor modulators (agents must be stopped prior to randomization)
  • Presence of neuropathy > grade 2 (NCI-CTC version 3.0) at baseline
  • Presence of any non-healing wound, bone fracture, or ulcer, or the presence of clinically significant (> grade 2) peripheral vascular disease
  • History of any other malignancy within the past 5 years, with the exception of non-melanoma skin cancer or carcinoma-in-situ of the cervix
  • Clinically significant cardiovascular disease (e.g., hypertension [BP > 150/100], myocardial infarction or stroke within 6 months, unstable angina), New York Heart Association (NYHA) Grade II or greater congestive heart failure, or serious cardiac arrhythmia requiring medication
  • Active peptic ulcer disease, inflammatory bowel disease, or other gastrointestinal condition increasing the risk of perforation; history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to beginning therapy
  • Active, uncontrolled infection requiring parenteral antimicrobials
  • The presence of any other medical or psychiatric disorder that, in the opinion of the treating physician, would contraindicate the use of the drugs in this protocol or place the subject at undue risk for treatment complications
  • Pregnancy or lactation
  • A history of a severe hypersensitivity reaction to bevacizumab, or docetaxel or other drugs formulated with polysorbate 80
  • Evidence of bleeding diathesis or coagulopathy
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to beginning therapy, or anticipation of the need for a major surgical procedure during the course of the study; minor surgical procedure, fine needle aspiration, or core biopsy within 7 days prior to beginning therapy
  • Urine protein:creatinine ratio of > 1.0 at screening

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Bevacizumab 7.5 and TAC
one dose of Bevacizumab (7.5mg/kg) will be administered intravenously every 3 weeks followed by TAC.
Drug: Bevacizumab 7.5 and TAC
Bevacizumab given intravenously at a dose of 7.5mg/kg every 3 weeks, followed by docetaxel, doxorubicin and cyclophosphamide (TAC).
Placebo Comparator: Placebo 7.5 and TAC
Placebo7.5 will be administered intravenously every 3 weeks followed by TAC.
Drug: Placebo 7.5 and Docetaxel, Doxorubicin, and Cyclophosphamide (TAC)
placebo 7.5 will be adminitered intravenously every 3 weeks followed by TAC
Experimental: Bevacizumab 15 and TAC
one dose of Bevacizumab (15mg/kg) will be administered intravenously every 3 weeks followed by TAC.
Drug: Bevacizumab 15 and TAC
one dose of Bevacizumab (15 mg/kg) will be administered intravenously every 3 weeks followed by TAC.
Placebo Comparator: Placebo 15 and TAC
Placebo 15mg/kg will be administered intravenously every 3 weeks followed by TAC.
Drug: Placebo 15 and TAC
one dose of placebo 15 will be administered intravenously every 3 weeks followed by TAC.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
•To evaluate the safety and toxicity of the TAC regimen with the addition of bevacizumab given as preoperative therapy to patients with Stage II or Stage III breast cancer
Time Frame: 4 years
Patients will be evaluated for adverse events (all grades) at each study visit for the duration of their participation in the study. All AEs should be graded using the NCI--CTCAE, Version 3.0. Patients discontinued from the treatment phase of the study for any reason will be evaluated within 30 days after the decision to discontinue treatment.
4 years
•To estimate change from baseline expression of HIF1α as a measure of tumor angiogenesis, after a single dose of bevacizumab as compared to placebo
Time Frame: 4 years
4 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
•To estimate the rate of CHF in patients receiving TAC with or without bevacizumab
Time Frame: 4 years
4 years
•To estimate the rates of left ventricular ejection fraction (LVEF) changes as measured by either a decrease of > 15% from baseline, or > 10% to a value below the lower limit of normal (for the institution), in patients receiving TAC or TAC + bevacizumab
Time Frame: 4 years
4 years
•To investigate the clinical efficacy of TAC and TAC plus bevacizumab by estimating the clinical objective response rate (CR + PR), pathologic complete response rate (pCR), and rate of breast-conserving surgery (BCS)
Time Frame: 4 years
4 years
•To estimate the rate of post-surgical wound healing complications in patients who receive surgery after TAC or TAC plus bevacizumab
Time Frame: 4 years
4 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Translational Oncology Research International

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Genentech, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Fairooz Kabbinavar, MD, Chief Medical Officer

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2005

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2012

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 12, 2005

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 12, 2005

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 20, 2005

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 12, 2015

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 9, 2015

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2011

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • TORI B-02
  • 10-001419 (Other Identifier: JCCC IRB)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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