Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Neoadjuvant TAC Plus or Minus Bevacizumab(AVF3299)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00203372
Recruitment Status : Completed
First Posted : September 20, 2005
Last Update Posted : October 12, 2015
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
Translational Oncology Research International

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.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Bevacizumab 7.5 and TAC Drug: Placebo 7.5 and Docetaxel, Doxorubicin, and Cyclophosphamide (TAC) Drug: Bevacizumab 15 and TAC Drug: Placebo 15 and TAC Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Study Start Date : May 2005
Actual Primary Completion Date : June 2012


Arm Intervention/treatment
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.




Primary Outcome Measures :
  1. •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.

  2. •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 ]

Secondary Outcome Measures :
  1. •To estimate the rate of CHF in patients receiving TAC with or without bevacizumab [ Time Frame: 4 years ]
  2. •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 ]
  3. •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. •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 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00203372


Locations
Layout table for location information
United States, California
UCLA Medical Center
Los Angeles, California, United States, 90095
Wilshire Oncology Medical Group, Inc.
Pomona, California, United States, 91767
United States, Florida
Cancer Institute of Florida, P.A.
Orlando, Florida, United States, 32804
United States, Georgia
Northwest Georgia Oncology Centers, P.C.
Marietta, Georgia, United States, 30060
United States, Texas
South Texas Oncology and Hematology, P.A.
San Antonio, Texas, United States, 78207
Canada, Alberta
Cross Cancer Institute
Edmonton, Alberta, Canada, T6G 1Z2
Canada, Quebec
McGill University
Montreal, Quebec, Canada, H2W 1S6
Ireland
St. Vincent's University Hospital
Dublin, Ireland, 4
St. James's Hospital
Dublin, Ireland, 8
Sponsors and Collaborators
Translational Oncology Research International
Genentech, Inc.
Investigators
Layout table for investigator information
Study Chair: Fairooz Kabbinavar, MD Chief Medical Officer

Layout table for additonal information
Responsible Party: Translational Oncology Research International
ClinicalTrials.gov Identifier: NCT00203372     History of Changes
Obsolete Identifiers: NCT00128674
Other Study ID Numbers: TORI B-02
10-001419 ( Other Identifier: JCCC IRB )
First Posted: September 20, 2005    Key Record Dates
Last Update Posted: October 12, 2015
Last Verified: February 2011

Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Bevacizumab
Cyclophosphamide
Docetaxel
Doxorubicin
Liposomal doxorubicin
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors