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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Breast Neoplasms
• Intervention / Treatment: Drug: Bevacizumab; Drug: Anastrozole; Drug: Fulvestrant

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.

• Study Type: Interventional
• Enrollment (Actual): 79
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Fort Myers, Florida, United States, 33901
      • Florida Cancer Specialists
    • Jacksonville, Florida, United States, 32256
      • Integrated Community Oncology Network
    • Orlando, Florida, United States, 32804
      • Florida Hospital Cancer Institute
  • Georgia
    • Gainesville, Georgia, United States, 30501
      • Northeast Georgia Medical Center
    • Marietta, Georgia, United States, 30060
      • Wellstar Cancer Research
  • Kentucky
    • Bowling Green, Kentucky, United States, 42101
      • Graves-Gilbert Clinic
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70806
      • Baton Rouge General Medical Center
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • St. Louis Cancer Care
  • Montana
    • Great Falls, Montana, United States, 59405
      • Sletten Cancer Institute
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Chattanooga Oncology & Hematology Associates
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology, PLLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: Avastin; Drug: Anastrozole; anastrozole (1 mg orally daily); Other Names: 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 Names: 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 Names: Faslodex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: SCRI Development Innovations, LLC
• Collaborators: AstraZeneca; Genentech, Inc.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: November 1, 2006
• Primary Completion (Actual): June 1, 2010
• Study Completion (Actual): June 1, 2011

Study Registration Dates

• First Submitted: November 28, 2006
• First Submitted That Met QC Criteria: November 28, 2006
• First Posted (Estimate): November 30, 2006

Study Record Updates

• Last Update Posted (Actual): November 18, 2021
• Last Update Submitted That Met QC Criteria: November 16, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: Bevacizumab; Breast cancer; Metastatic breast cancer; Fulvestrant; Anastrozole
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Estrogen Receptor Antagonists; Fulvestrant; Bevacizumab; Anastrozole
• Other Study ID Numbers: SCRI BRE 86