Bevacizumab Given With Either Anastrozole or Fulvestrant With Trastuzumab for Postmenopausal Metastatic Breast Cancer
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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) |
- 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.
- 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 |
| Estimated Study Completion Date: | June 2013 |
| Primary Completion Date: | June 2011 (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 |
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| 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 | |
| Principal Investigator: | Denise A Yardley, MD | Sarah Cannon Research Institute |
More Information
Publications:
| Responsible Party: | Sarah Cannon Research Institute |
| 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: | February 12, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Sarah Cannon Research Institute:
|
Breast cancer Metastatic breast cancer Bevacizumab Anastrozole Fulvestrant |
Additional relevant MeSH terms:
|
Breast Neoplasms Neoplasms Neoplasms by Site Breast Diseases Skin Diseases Fulvestrant Anastrozole Trastuzumab Bevacizumab Estradiol Antineoplastic Agents Therapeutic Uses Pharmacologic Actions Estrogen Antagonists |
Estrogen Receptor Modulators Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Antineoplastic Agents, Hormonal Estrogens Hormones Aromatase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Growth Inhibitors |
ClinicalTrials.gov processed this record on June 18, 2013