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

This study has been completed.
Sponsor:
Collaborators:
Genentech
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
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Breast Neoplasms
Drug: Bevacizumab
Drug: Anastrozole
Drug: Fulvestrant
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by SCRI Development Innovations, LLC:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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


Enrollment: 79
Study Start Date: November 2006
Study Completion Date: June 2011
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Bevacizumab
Bevacizumab 10mg/kg IV every 2 weeks
Other Name: Avastin
Drug: Anastrozole
anastrozole (1 mg orally daily)
Other Name: Arimidex
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.
Drug: Bevacizumab
Bevacizumab 10mg/kg IV every 2 weeks
Other Name: Avastin
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.

  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: NCT00405938

Locations
United States, Florida
Florida Cancer Specialists
Fort Myers, Florida, United States, 33901
Integrated Community Oncology Network
Jacksonville, Florida, United States, 32256
Florida Hospital Cancer Institute
Orlando, Florida, United States, 32804
United States, Georgia
Northeast Georgia Medical Center
Gainesville, Georgia, United States, 30501
Wellstar Cancer Research
Marietta, Georgia, United States, 30060
United States, Kentucky
Graves-Gilbert Clinic
Bowling Green, Kentucky, United States, 42101
United States, Louisiana
Baton Rouge General Medical Center
Baton Rouge, Louisiana, United States, 70806
United States, Missouri
St. Louis Cancer Care
Chesterfield, Missouri, United States, 63017
United States, Montana
Sletten Cancer Institute
Great Falls, Montana, United States, 59405
United States, Tennessee
Chattanooga Oncology & Hematology Associates
Chattanooga, Tennessee, United States, 37404
Tennessee Oncology, PLLC
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
SCRI Development Innovations, LLC
Genentech
AstraZeneca
Investigators
Principal Investigator: Denise A Yardley, MD SCRI Development Innovations, LLC
  More Information

Publications:
Responsible Party: SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier: NCT00405938     History of Changes
Other Study ID Numbers: SCRI BRE 86
Study First Received: November 28, 2006
Results First Received: January 11, 2013
Last Updated: December 5, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by SCRI Development Innovations, LLC:
Breast cancer
Metastatic breast cancer
Bevacizumab
Anastrozole
Fulvestrant

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Bevacizumab
Trastuzumab
Anastrozole
Fulvestrant
Estradiol
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Hormonal
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Estrogens
Hormones

ClinicalTrials.gov processed this record on September 18, 2014