Bevacizumab Given With Either Anastrozole or Fulvestrant With Trastuzumab for Postmenopausal Metastatic Breast Cancer

This study has been completed.
Sponsor:
Collaborators:
Genentech, Inc.
AstraZeneca
Information provided by (Responsible Party):
SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier:
NCT00405938
First received: November 28, 2006
Last updated: December 5, 2013
Last verified: December 2013

November 28, 2006
December 5, 2013
November 2006
June 2010   (final data collection date for primary outcome measure)
Progression Free Survival (PFS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Worsening of Their Disease [ Time Frame: 18 months ] [ Designated as safety issue: No ]
Defined as the interval, in months, from the date of first treatment to the date of disease progression or death, whichever occurred first.
To assess the time to disease progression of the combination of bevacizumab with anastrozole or fulvestrant in hormone dependent metastatic breast cancer.
Complete list of historical versions of study NCT00405938 on ClinicalTrials.gov Archive Site
Objective Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment [ Time Frame: 18 months ] [ Designated as safety issue: No ]
The Percentage of Patients Who Experience an Objective Benefit From Treatment
  • To assess the response rate and clinical benefit rate of the different combinations of drugs.
  • To assess the feasibility and toxicity of this combination in hormone dependent breast cancer patients
  • To assess overall survival
Not Provided
Not Provided
 
Bevacizumab Given With Either Anastrozole or Fulvestrant With Trastuzumab for Postmenopausal Metastatic Breast Cancer
A Phase II Trial of Open-Label Bevacizumab Administered With Anastrozole or Fulvestrant as First-Line Therapy in Postmenopausal Hormone Receptor- Positive Metastatic Breast Cancer (With Trastuzumab in HER2-Positive Patients)

This is a phase II trial combining bevacizumab with either fulvestrant or anastrozole with trastuzumab in the treatment of metastatic breast cancer in postmenopausal women. It is hoped that these combinations will keep the cancer from growing and spreading further.

Regimen A: Bevacizumab/anastrozole (with trastuzumab in HER2+ patients). Bevacizumab 10mg/kg IV every 2 weeks [patients who are also receiving trastuzumab have the option to receive their bevacizumab at 15 mg/kg every 3 weeks instead of 10 mg/kg every 2 weeks (see Trastuzumab section below)] and anastrozole (1 mg orally daily). Treatment will be given in 4-week cycles. Response assessments will be performed after 2 cycles. Patients who respond to treatment or have stable disease will continue to be evaluated every 2 cycles. After 6 months, response assessment will occur every 3 months. A patient may remain on study if radiation is deemed necessary and appropriate, provided that there are other sites of measurable disease outside the field of radiation that may be followed. Treatment occurs until disease progression. Patients will be selected for this treatment arm per the following guidelines: >=12 months from adjuvant endocrine therapy OR >=12 months from adjuvant aromatase inhibitors OR Endocrine therapy naive OR Prior tamoxifen exposure or tamoxifen intolerance

Regimen B: Bevacizumab/fulvestrant (with trastuzumab in HER2+ patients). Bevacizumab 10mg/kg IV every 2 weeks [patients who are also receiving trastuzumab have the option to receive their bevacizumab at 15 mg/kg every 3 weeks instead of 10 mg/kg every 2 weeks (see Trastuzumab section below)] fulvestrant (500 mg intramuscular on Day 1 of Cycle 1, followed by 250 mg intramuscular of fulvestrant on Day 15 of Cycle 1. On Day 1 of Cycle 2 and the first day of all subsequent cycles thereafter, patients in this treatment arm will receive 250 mg intramuscularly of fulvestrant). Treatment will be given in 4-week cycles. Response assessments will be performed after 2 cycles. Patients who respond to treatment or have stable disease will continue to be evaluated every 2 cycles. After 6 months, response assessment will occur every 3 months. A patient may remain on study if radiation is deemed necessary and appropriate, provided that there are other sites of measurable disease outside the field of radiation that may be followed. Treatment occurs until disease progression. Patients will be selected for this treatment arm per the following guidelines: <12 months from adjuvant aromatase inhibitor therapy OR Intolerant of aromatase inhibitors OR Disease progression on adjuvant aromatase inhibitors OR Physician discretion

Trastuzumab: Patients in Treatment Arm A or Treatment Arm B who have FISH HER2+ or IHC3+ breast cancer will also receive treatment with trastuzumab in addition to their treatment with the combination of bevacizumab with either anastrozole or fulvestrant. Trastuzumab will be administered ONLY to patients with HER2+ breast cancer (FISH-positive or IHC3+). An 8 mg/kg loading dose of IV trastuzumab will be administered on Day 1, followed by doses of 6 mg/kg IV trastuzumab once every 3 weeks. These patients will have the option of receiving their bevacizumab doses at 15 mg/kg every 3 weeks rather than 10 mg/kg every 2 weeks (if they prefer to keep their bevacizumab dosing schedule consistent with their trastuzumab dosing schedule so that the number of visits they must make to the study site is minimized). The dosing schedules for anastrozole (for HER2+ patients in Treatment Arm A) and fulvestrant (for HER2+ patients in Treatment Arm B) will not change.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Breast Cancer
  • Breast Neoplasms
  • Drug: Bevacizumab
    Bevacizumab 10mg/kg IV every 2 weeks
    Other Name: Avastin
  • Drug: Anastrozole
    anastrozole (1 mg orally daily)
    Other Name: Arimidex
  • Drug: Fulvestrant
    fulvestrant (500 mg IM on Day 1 of Cycle 1, followed by 250 mg IM of fulvestrant on Day 15 of Cycle 1. On Day 1 of Cycle 2 and the first day of all subsequent cycles thereafter, patients in this treatment arm will receive 250 mg IM of fulvestrant).
    Other Name: Faslodex
  • Experimental: Bevacizumab/anastrozole
    Bevacizumab 10mg/kg IV every 2 weeks [patients who are also receiving trastuzumab have the option to receive their bevacizumab at 15 mg/kg every 3 weeks instead of 10 mg/kg every 2 weeks (see Trastuzumab section below)] and anastrozole (1 mg orally daily). Treatment will be given in 4-week cycles.
    Interventions:
    • Drug: Bevacizumab
    • Drug: Anastrozole
  • Experimental: Bevacizumab/fulvestrant
    Bevacizumab/fulvestrant (with trastuzumab in HER2+ patients). Bevacizumab 10mg/kg IV every 2 weeks [patients who are also receiving trastuzumab have the option to receive their bevacizumab at 15 mg/kg every 3 weeks instead of 10 mg/kg every 2 weeks (see Trastuzumab section below)] fulvestrant (500 mg IM on Day 1 of Cycle 1, followed by 250 mg IM of fulvestrant on Day 15 of Cycle 1. On Day 1 of Cycle 2 and the first day of all subsequent cycles thereafter, patients in this treatment arm will receive 250 mg IM of fulvestrant). Treatment will be given in 4-week cycles.
    Interventions:
    • Drug: Bevacizumab
    • Drug: Fulvestrant
Yardley DA, Burris HA 3rd, Clark BL, Shipley D, Rubin M, Barton J Jr, Arrowsmith E, Hainsworth JD. Hormonal therapy plus bevacizumab in postmenopausal patients who have hormone receptor-positive metastatic breast cancer: a phase II Trial of the Sarah Cannon Oncology Research Consortium. Clin Breast Cancer. 2011 Jun;11(3):146-52. doi: 10.1016/j.clbc.2011.03.010. Epub 2011 Apr 20.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
79
June 2011
June 2010   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Postmenopausal breast cancer (adenocarcinoma) estrogen (ER)and/or progesterone (PR) receptor positive that is locally advanced or locally recurrent and not able to be surgically removed OR with measurable and/or disease that is able to be assessed including isolated bone metastasis
  • Female patients 18 years or older
  • Documentation of ER+ and/or PR+
  • No prior chemotherapy or hormone therapy for metastatic breast cancer or inoperable breast cancer that is locally recurrent or locally advanced
  • Measurable or evaluable disease
  • Radiation therapy to painful bone lesions or impending fractures is allowed as long as there is measurable or evaluable disease outside the radiated area.
  • Must have adequate bone marrow, renal and liver function
  • Patients receiving prior treatment with an anthracycline based chemotherapy must have a normal left ventricle ejection fraction

Exclusion Criteria:

  • No metastatic disease to the Central Nervous System
  • No history of myocardial infarction (MI), stroke or transient ischemic attacks in the last 6 months
  • No symptoms of peripheral vascular disease
  • No history of abdominal fistula, gastrointestinal perforation or intrabdominal abscess in the past 6 months
  • No known hypersensitivity to phosphate, trehalose or polysorbate
  • No serious non-healing wound, ulcer or bone fracture
  • No uncontrolled high blood pressure or history of hypertensive crisis
  • No New York Hear Association class II congestive heart failure
  • No extensive cancer involvement of the liver or lungs
  • No history of significant psychiatric disorders
  • No significant vascular disease

There are additional inclusion/exclusion criteria. The study center will determine if you meet all of the criteria. If you do not qualify for the trial, study personnel will explain the reasons. If you do qualify, study personnel will explain the trial in detail and answer any questions you may have. You can then decide if you wish to participate.

Female
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00405938
SCRI BRE 86
No
SCRI Development Innovations, LLC
SCRI Development Innovations, LLC
  • Genentech, Inc.
  • AstraZeneca
Principal Investigator: Denise A Yardley, MD SCRI Development Innovations, LLC
SCRI Development Innovations, LLC
December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP