Neoadjuvant TAC Plus or Minus Bevacizumab(AVF3299)

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00203372
• Other study ID #: TORI B-02
• Secondary ID: 10-001419
• Status: Completed
• Phase: Phase 2
• First received: September 12, 2005
• Last updated: October 9, 2015
• Start date: May 2005

Study information

• Verified date: February 2011
• Source: Translational Oncology Research International
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00128674

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. primary completion date: June 2012
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

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 7.5 and Docetaxel, Doxorubicin, and Cyclophosphamide (TAC)
placebo 7.5 will be adminitered intravenously every 3 weeks followed by TAC
• Bevacizumab 15 and TAC
one dose of Bevacizumab (15 mg/kg) will be administered intravenously every 3 weeks followed by TAC.
• Placebo 15 and TAC
one dose of placebo 15 will be administered intravenously every 3 weeks followed by TAC.

Locations

Country	Name	City	State
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	McGill University	Montreal	Quebec
Ireland	St. James's Hospital	Dublin
Ireland	St. Vincent's University Hospital	Dublin
United States	UCLA Medical Center	Los Angeles	California
United States	Northwest Georgia Oncology Centers, P.C.	Marietta	Georgia
United States	Cancer Institute of Florida, P.A.	Orlando	Florida
United States	Wilshire Oncology Medical Group, Inc.	Pomona	California
United States	South Texas Oncology and Hematology, P.A.	San Antonio	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Translational Oncology Research International	Genentech, Inc.

Countries where clinical trial is conducted

United States,  Canada,  Ireland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	•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
Primary	•To estimate change from baseline expression of HIF1a as a measure of tumor angiogenesis, after a single dose of bevacizumab as compared to placebo		4 years
Secondary	•To estimate the rate of CHF in patients receiving TAC with or without bevacizumab		4 years
Secondary	•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
Secondary	•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
Secondary	•To estimate the rate of post-surgical wound healing complications in patients who receive surgery after TAC or TAC plus bevacizumab		4 years