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

Breast Cancer Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00405938
• Other study ID #: SCRI BRE 86
• Status: Completed
• Phase: Phase 2
• Start date: November 2006
• Est. completion date: June 2011

Study information

• Verified date: November 2021
• Source: SCRI Development Innovations, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 79
• Est. completion date: June 2011
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Bevacizumab
Bevacizumab 10mg/kg IV every 2 weeks
• Anastrozole
anastrozole (1 mg orally daily)
• 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).

Locations

Country	Name	City	State
United States	Baton Rouge General Medical Center	Baton Rouge	Louisiana
United States	Graves-Gilbert Clinic	Bowling Green	Kentucky
United States	Chattanooga Oncology & Hematology Associates	Chattanooga	Tennessee
United States	St. Louis Cancer Care	Chesterfield	Missouri
United States	Florida Cancer Specialists	Fort Myers	Florida
United States	Northeast Georgia Medical Center	Gainesville	Georgia
United States	Sletten Cancer Institute	Great Falls	Montana
United States	Integrated Community Oncology Network	Jacksonville	Florida
United States	Wellstar Cancer Research	Marietta	Georgia
United States	Tennessee Oncology, PLLC	Nashville	Tennessee
United States	Florida Hospital Cancer Institute	Orlando	Florida

Sponsors (3)

Lead Sponsor	Collaborator
SCRI Development Innovations, LLC	AstraZeneca, Genentech, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Progression Free Survival (PFS) is defined as the interval, in months, from the date of first treatment to the date of disease progression or death, whichever occurred first.	18 months
Secondary	Objective Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment	The Percentage of Patients Who Experience an Objective Benefit From Treatment (CR+PR). The response categories were assigned using RECIST criteria. Complete Response (CR) = Disappearance of all target lesions ; Partial Response (PR) = >=30% decrease in the sum of the longest diameter of target lesions.	18 months