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A Study of Bevacizumab (Avastin) in Women With HER2 Negative Metastatic Breast Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00333775
First received: June 5, 2006
Last updated: December 21, 2015
Last verified: December 2015
  Purpose
This study will evaluate the efficacy and safety of 2 doses of Avastin in combination with docetaxel, versus docetaxel plus placebo, in patients with metastatic HER2 negative breast cancer who are candidates for taxane-based chemotherapy but who have not received prior chemotherapy for metastatic disease. The anticipated time on treatment is 1-2 years and the target sample size is 500+ individuals.

Condition Intervention Phase
Breast Cancer
Drug: Docetaxel
Drug: Placebo to bevacizumab
Drug: Bevacizumab
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomised, Double Blind, Placebo Controlled, Multicentre Study to Evaluate the Efficacy and Safety of Bevacizumab in Combination With Docetaxel in Comparison With Docetaxel Plus Placebo, as First Line Treatment for Patients With HER2 Negative Metastatic and Locally Recurrent Breast Cancer.

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Progression-free Survival [ Time Frame: Baseline to the 15 Sep 2008 cut-off date (up to 2 years, 6 months) ] [ Designated as safety issue: No ]
    Progression-free survival was evaluated using Response Evaluation Criteria In Solid Tumors (RECIST 1.0). Progression-free survival was defined as the time from randomization to the time of the first documented disease progression or death, whichever occurred first. Disease progression was defined as ≥ 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the unequivocal progression of existing non-target lesions, or appearance of new lesion(s).


Secondary Outcome Measures:
  • Percentage of Participants With a Complete Response or a Partial Response [ Time Frame: Baseline to the 15 Sep 2008 cut-off date (up to 2 years, 6 months) ] [ Designated as safety issue: No ]
    Responses were evaluated using the Response Evaluation Criteria in Solid Tumors. A complete response was defined as the disappearance of all target lesions or the disappearance of all non-target lesions and normalization of tumor marker level. A partial response was defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter.

  • Duration of Response [ Time Frame: Baseline to the 15 September 2008 cut-off date (up to 2 years, 6 months) ] [ Designated as safety issue: No ]
    Duration of response was defined as the time from the first documented complete response or partial response to disease progression or death. A complete response was defined as the disappearance of all target lesions or the disappearance of all non-target lesions and normalization of tumor marker level. A partial response was defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. Responses were evaluated using the Response Evaluation Criteria in Solid Tumors.

  • Time to Treatment Failure [ Time Frame: Baseline to the 15 September 2008 cut-off date (up to 2 years, 6 months) ] [ Designated as safety issue: No ]
    Time to treatment failure was defined as time from randomization to the date of disease progression, death, or withdrawal of treatment due to an adverse event, withdrawal of informed consent, insufficient therapeutic response, refusal of treatment/failure to co-operate, or failure to return, whichever occurred first.

  • Overall Survival [ Time Frame: Baseline to the 15 Sep 2008 cut-off date (up to 2 years, 6 months) ] [ Designated as safety issue: No ]
    Overall survival was defined as the time from randomization to death from any cause.


Enrollment: 736
Study Start Date: March 2006
Study Completion Date: October 2013
Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Docetaxel 100 mg/m^2 plus placebo
Participants received docetaxel 100 mg/m^2 intravenously on Day 1 of each 3 week cycle for a maximum of 27 weeks (9 cycles). In addition, participants received placebo to bevacizumab intravenously on Day 1 of each 3 week cycle until disease progression, unacceptable toxicity, or participant withdrawal.
Drug: Docetaxel
Docetaxel was supplied in 2 vials, 1 containing docetaxel and 1 containing a solvent, for intravenous infusion.
Drug: Placebo to bevacizumab
Placebo to bevacizumab was supplied as a sterile liquid for intravenous infusion in single-use vials.
Experimental: Docetaxel 100 mg/m^2 plus bevacizumab 7.5 mg/kg
Participants received docetaxel 100 mg/m^2 intravenously on Day 1 of each 3 week cycle for a maximum of 27 weeks (9 cycles). In addition, participants received bevacizumab 7.5 mg/kg intravenously on Day 1 of each 3 week cycle until disease progression, unacceptable toxicity, or participant withdrawal.
Drug: Docetaxel
Docetaxel was supplied in 2 vials, 1 containing docetaxel and 1 containing a solvent, for intravenous infusion.
Drug: Bevacizumab
Bevacizumab was supplied as a sterile liquid for intravenous infusion in single-use vials.
Other Name: Avastin
Experimental: Docetaxel 100 mg/m^2 plus bevacizumab 15.0 mg/kg
Participants received docetaxel 100 mg/m^2 intravenously on Day 1 of each 3 week cycle for a maximum of 27 weeks (9 cycles). In addition, participants received bevacizumab 15.0 mg/kg intravenously on Day 1 of each 3 week cycle until disease progression, unacceptable toxicity, or participant withdrawal.
Drug: Docetaxel
Docetaxel was supplied in 2 vials, 1 containing docetaxel and 1 containing a solvent, for intravenous infusion.
Drug: Bevacizumab
Bevacizumab was supplied as a sterile liquid for intravenous infusion in single-use vials.
Other Name: Avastin

Detailed Description:
Five participants randomized to the docetaxel 100 mg/m^2 plus placebo group actually received docetaxel 100 mg/m^2 plus bevacizumab 7.5 mg/kg and are included in the docetaxel 100 mg/m^2 plus bevacizumab 7.5 mg/kg group for the adverse event results. Sixteen participants randomized to the docetaxel 100 mg/m^2 plus placebo group actually received docetaxel 100 mg/m^2 plus bevacizumab 15.0 mg/kg and are included in the docetaxel 100 mg/m^2 plus bevacizumab 15.0 mg/kg group for the adverse event results.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Female patients ≥ 18 years of age.
  • Human epidermal growth factor receptor 2 (HER2)-negative cancer of the breast with locally recurrent or metastatic disease, suitable for chemotherapy.
  • No adjuvant chemotherapy within 6 months before randomization, and no taxane-based chemotherapy within 12 months before randomization.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

Exclusion criteria:

  • Previous chemotherapy for metastatic or locally recurrent breast cancer.
  • Radiotherapy for treatment of metastatic disease.
  • Other primary tumors within last 5 years, except for controlled limited basal cell or squamous cancer of the skin, or cancer in situ of the cervix.
  • Spinal cord compression or brain metastases.
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to randomization.
  • Inadequate bone marrow, liver, or renal function.
  • Uncontrolled hypertension.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00333775

  Show 114 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00333775     History of Changes
Other Study ID Numbers: BO17708  2005-003862-40 
Study First Received: June 5, 2006
Results First Received: July 22, 2015
Last Updated: December 21, 2015
Health Authority: France: AFSSAPS (Agence francaise de securite sanitaire des produits de Sante)

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Docetaxel
Bevacizumab
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on December 02, 2016