Neoadjuvant TAC Plus or Minus Bevacizumab(AVF3299)

NCT00203372 | Completed Phase 2 DMC

• 2 other identifiers: TORI B-0210-001419
• Study Type: interventional
• Target: 6
• Locations: 3 countries
• Sites: 9

Brief Summary

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.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (2)

• •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

  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

  4 years

Secondary Outcomes (4)

• •To estimate the rate of CHF in patients receiving TAC with or without bevacizumab

  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

  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)

  4 years

• •To estimate the rate of post-surgical wound healing complications in patients who receive surgery after TAC or TAC plus bevacizumab

  4 years

Study Arms (4)

Bevacizumab 7.5 and TAC

EXPERIMENTAL

one dose of Bevacizumab (7.5mg/kg) will be administered intravenously every 3 weeks followed by TAC.

Drug: Bevacizumab 7.5 and TAC

Placebo 7.5 and TAC

PLACEBO COMPARATOR

Placebo7.5 will be administered intravenously every 3 weeks followed by TAC.

Drug: Placebo 7.5 and Docetaxel, Doxorubicin, and Cyclophosphamide (TAC)

Bevacizumab 15 and TAC

EXPERIMENTAL

one dose of Bevacizumab (15mg/kg) will be administered intravenously every 3 weeks followed by TAC.

Drug: Bevacizumab 15 and TAC

Placebo 15 and TAC

PLACEBO COMPARATOR

Placebo 15mg/kg will be administered intravenously every 3 weeks followed by TAC.

Drug: Placebo 15 and TAC

Interventions

Bevacizumab 7.5 and TAC DRUG

Bevacizumab given intravenously at a dose of 7.5mg/kg every 3 weeks, followed by docetaxel, doxorubicin and cyclophosphamide (TAC).

Bevacizumab 7.5 and TAC

Placebo 7.5 and Docetaxel, Doxorubicin, and Cyclophosphamide (TAC) DRUG

placebo 7.5 will be adminitered intravenously every 3 weeks followed by TAC

Placebo 7.5 and TAC

Bevacizumab 15 and TAC DRUG

one dose of Bevacizumab (15 mg/kg) will be administered intravenously every 3 weeks followed by TAC.

Bevacizumab 15 and TAC

Placebo 15 and TAC DRUG

one dose of placebo 15 will be administered intravenously every 3 weeks followed by TAC.

Placebo 15 and TAC

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Translational Oncology Research International: lead
• Genentech, Inc.: collaborator

Study Sites (9)

UCLA Medical Center

Los Angeles, California, 90095, United States

Location

Wilshire Oncology Medical Group, Inc.

Pomona, California, 91767, United States

Location

Cancer Institute of Florida, P.A.

Orlando, Florida, 32804, United States

Location

Northwest Georgia Oncology Centers, P.C.

Marietta, Georgia, 30060, United States

Location

South Texas Oncology and Hematology, P.A.

San Antonio, Texas, 78207, United States

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

McGill University

Montreal, Quebec, H2W 1S6, Canada

Location

St. Vincent's University Hospital

Dublin, 4, Ireland

Location

St. James's Hospital

Dublin, 8, Ireland

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Docetaxel; Doxorubicin; Cyclophosphamide

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; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds

Study Officials

• Fairooz Kabbinavar, MD

  Chief Medical Officer

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: September 12, 2005
• First Posted: September 20, 2005
• Study Start: May 1, 2005
• Primary Completion: June 1, 2012
• Last Updated: October 12, 2015

Record last verified: 2011-02

Locations

IE (2); US (5); CA (2)