Breast Cancer, Breast Neoplasm, Cancer of the Breast
Conditions
Keywords
Hormonal and antibody therapy for breast cancer, Hormonal therapy for breast cancer, Antibody therapy for breast cancer
Brief summary
This purpose of this trial is to show that the combination of Avastin and hormone therapy should be more effective than hormone therapy alone for the treatment of breast cancer.
Detailed description
Preclinical and clinical data have demonstrated that up-regulation of tumor cell VEGF is an important mechanism to subvert estrogen dependence in hormone responsive breast cancer resulting in reduced therapy response or tumor resistance to hormonal therapy; thus, it is hypothesized that the combination of an anti-VEGF agent (Avastin, an anti-VEGF monoclonal antibody) and hormonal therapy should be more effective than hormonal therapy alone for the treatment of breast cancer.
Interventions
OTHERLetrozole (Femara)
Letrozole 2.5 mg PO a day for 24 weeks
DRUGLetrozole; Avastin
Letrozole 2.5 mg PO a day and Avastin 15 mg/kg IV every 3 weeks
Sponsors
Genentech, Inc.
Breast Cancer Research Foundation
University of Alabama at Birmingham
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
All patients must meet the following criteria to be eligible for study entry: * Pathologically confirmed invasive ductal carcinoma or invasive lobular carcinoma of the breast, T2-T3 / T4a-c / N0-2 / M0, with positive estrogen and/or progesterone receptors, and Her-2-neu negative. Patients with inflammatory breast cancer will not be included (T4d). Patients previously treated patients with no measurable disease or patients with metastatic disease will be excluded. * Give written informed consent prior to study specific screening procedures, with the understanding that the patient has the right to withdraw from the study at any time, without prejudice. * Patients must be postmenopausal, defined as one of the following: * Patients \> 50 years of age with no spontaneous menses for at least 12 months, * Bilateral oophorectomy * Be ambulatory (outpatient) and have an ECOG PS \<1. * Patients must have measurable disease by mammogram and/or breast ultrasound (in special cases a dedicated breast MRI may be clinically indicated). The target lesion must not have been previously irradiated. * No prior chemotherapy. * Patients must have adequate organ and marrow function as defined as follows: absolute neutrophil count \> 1,500/mm3, hemoglobin \> 8.0 g/dl, platelets \> 75,000/mm3, total bilirubin \< 2 mg/dl, serum creatinine \< 2 mg/dl, Transaminases (AST, ALT) may be up to 2 x institutional upper limit of normal. In addition \< 1 gr of protein in 24 hr urine collection and urine protein/creatinine ratio \< 1.0. * No life threatening parenchymal disease or rapidly progressing disease warranting cytotoxic chemotherapy. * Hypertension must be controlled (\<150/100 mmHg). * Ejection Fraction \> 50% by echocardiogram. (LVEF greater than 75% at baseline should be reviewed and/or the test repeated as it may be falsely elevated). * No history of thrombosis during the previous 12 months.
Exclusion criteria
* Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than this sponsor-investigator Bevacizumab cancer study. * Uncontrolled high blood pressure (\>150/100 mmHg). * Unstable angina * New York Heart Association (NYHA) Grade III or greater congestive heart failure * History of myocardial infarction or unstable angina within 12 months * History of stroke or TIA within 12 months * Clinically significant peripheral vascular disease * History of a bleeding disorder * Presence of central nervous system or brain metastases * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, anticipation of need for major surgical procedure during the course of the study * Minor surgical procedures (excluding fine needle aspirations or core biopsies) within 5 days prior to Day 0 * Pregnant (positive pregnancy test) or lactating * Urine protein: creatinine ratio greater than or equal to 1.0 at screening or patients demonstrating \> 1 gr of protein in 24 hr urine collection within 4 weeks prior to study entry will not participate in the trial. * History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0 * Serious, non-healing wound, ulcer, or bone fracture * Unwilling or unable to comply with the protocol for the duration of the study. * Psychiatric illness/social situations that would limit compliance with study requirements. * History of another malignancy within the last five years except non-melanoma skin cancer and carcinoma in-situ of uterine cervix. * Patients with metastatic disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Participants With Pathologic Complete Response | 24 weeks | Pathological complete response is defined as the absence of residual invasive tumor in the breast or axillary lymph nodes or if only residual ductal carcinoma in-situ was seen on review of the surgical specimen. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Letrozole +Avastin | 24 weeks | Radiographic objective response to the therapy are reported. Radiographic response was assessed using RECIST criteria by ultrasound or breast MRI through the study and are reported as complete radiographic response below. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Letrozole + Avastin Letrozole; Avastin: Letrozole 2.5 mg PO a day and Avastin 15 mg/kg IV every 3 weeks | 50 |
| Letrozole Alone Letrozole (Femara): Letrozole 2.5 mg PO a day for 24 weeks | 25 |
| Total | 75 |
Baseline characteristics
| Characteristic | Letrozole + Avastin | Letrozole Alone | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 50 Participants | 25 Participants | 75 Participants |
| Age, Continuous | 58 years STANDARD_DEVIATION 0.5 | 58 years STANDARD_DEVIATION 0.5 | 58 years STANDARD_DEVIATION 0.5 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 3 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 40 Participants | 20 Participants | 60 Participants |
| Region of Enrollment United States | 50 Participants | 25 Participants | 75 Participants |
| Sex: Female, Male Female | 50 Participants | 25 Participants | 75 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Study Participant | 50 Participants | 25 Participants | 75 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 50 | 0 / 25 |
| other Total, other adverse events | 2 / 50 | 0 / 25 |
| serious Total, serious adverse events | 2 / 50 | 0 / 25 |
Outcome results
Primary
The Percentage of Participants With Pathologic Complete Response
Pathological complete response is defined as the absence of residual invasive tumor in the breast or axillary lymph nodes or if only residual ductal carcinoma in-situ was seen on review of the surgical specimen.
Time frame: 24 weeks
Population: Patients with postmenopausal hormone receptor positive breast cancer T2-4,N0-2 and M0 were randomized 2:1 to receive letrozole 2.5 mg PO daily and bevacizumab 15 mg/kg IV for 24 weeks or daily treatment with letrozole 2.5 mg PO alone (control arm). The duration of each cycle was 3 weeks for a total of 24 weeks. The pCR was defined as the absence of any residual invasive cancer in the resected breast specimen and lymph nodes. Data below is representative of the raw data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Letrozole + Avastin | The Percentage of Participants With Pathologic Complete Response | 11 percentage of participants |
| Letrozole Alone | The Percentage of Participants With Pathologic Complete Response | 0 percentage of participants |
Secondary
Letrozole +Avastin
Radiographic objective response to the therapy are reported. Radiographic response was assessed using RECIST criteria by ultrasound or breast MRI through the study and are reported as complete radiographic response below.
Time frame: 24 weeks
Population: This was a single arm study to test the feasibility of Letrozole with Avastin in the neoadjuvant setting.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Letrozole + Avastin | Letrozole +Avastin | 10 participants |
| Letrozole Alone | Letrozole +Avastin | 4 participants |