Clinical trial NCT00405938: Bevacizumab Given With Either Anastrozole or Fulvestrant With Trastuzumab for Postmenopausal Metastatic Breast Cancer
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Breast Neoplasms
Keywords: Breast cancer
Metastatic breast cancer
Bevacizumab
Anastrozole
Fulvestrant
Lead sponsor: SCRI Development Innovations, LLC
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
name: AstraZeneca
First posted: 2006-11-30
Enrollment: 79
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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 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.

Primary outcomes:
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
timeFrame: 18 months
Secondary outcomes:
measure: Objective Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment
timeFrame: 18 months
Other outcomes:
Locations:
city: Fort Myers
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Jacksonville
country: United States
facility: Integrated Community Oncology Network
state: Florida
city: Orlando
country: United States
facility: Florida Hospital Cancer Institute
state: Florida
city: Gainesville
country: United States
facility: Northeast Georgia Medical Center
state: Georgia
city: Marietta
country: United States
facility: Wellstar Cancer Research
state: Georgia
city: Bowling Green
country: United States
facility: Graves-Gilbert Clinic
state: Kentucky
city: Baton Rouge
country: United States
facility: Baton Rouge General Medical Center
state: Louisiana
city: Chesterfield
country: United States
facility: St. Louis Cancer Care
state: Missouri
city: Great Falls
country: United States
facility: Sletten Cancer Institute
state: Montana
city: Chattanooga
country: United States
facility: Chattanooga Oncology & Hematology Associates
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
Study officials:
affiliation: SCRI Development Innovations, LLC
name: Denise A Yardley, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.