Invasive Breast Cancer
Conditions
Keywords
hormone receptor positive, invasive breast cancer, endocrine therapy, Anastrazole, Fulvestrant, breast tumors, postmenopausal
Brief summary
This study is being done to test the safety and effectiveness of two drugs, Anastrozole and Fulvestrant, used as combined therapy in the neo-adjuvant setting for hormone receptor positive invasive breast cancer.
Detailed description
Hormonal therapies are generally preferred treatments of breast cancer because they have minimal side effects. Hormone receptor positive breast cancer generally does not respond very well to chemotherapy, which has many side effects. Hormonal therapy with a single drug such as Anastrozole is the main type of treatment used to reduce the risk of cancer recurrence. Whether a combination of Anastrazole nad Fulvestrant is effective and feasible is not known. This study is being done to answer this question. This is a phase II single arm study. Patients will have an Oncotype Dx performed and only if the recurrence score is low or intermediate, they would be eligible. Eligible patients will receive Anastrazole and Fulvestrant for 16 week. Subjects will receive Anastrazole 1 mg po q day and Fulvestrant 500 mg IM, day 1, day 14, day 28 and thereafter once every 28 days on outpatient basis. On day 28, subjects will be evaluated for side effects and clinically and a needle core biopsy (optional) will be obtained. If there is increase in Ki 67 by 50%, subjects will be taken off the study. Response evaluation will occur every 28 days during outpatient clinic visits. All treatment will continue until 4 months when patients will undergo surgical intervention. After surgery, patients will be off study and will receive additional breast cancer therapy at the discretion of their treating physician. Patients who develop progressive disease on protocol will be removed from the study and will then be treated at the discretion of the treating physician. The protocol will be closed after the last accrued patient has had surgery.
Interventions
DRUGFulvestrant
Fulvestrant IM on day 14 and on day 28 followed by day 28 of all subsequent cycles thereafter. Treatment will be continued for a total of 4 cycles.
DRUGAnastrazole
Anastrazole, 1mg by mouth every day of all 28 day cycles and continued for a total of 4 cycles
Sponsors
AstraZeneca
University of Kansas Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Female patient \> 18 years of age. * Histologically proven invasive adenocarcinoma of the breast. * Patients must be candidates for neoadjuvant treatment (Tumor size \> 2cm and/or clinical N1 or N2). * ER positive (\> 10% of cells) and/or PgR positive (\> 10% of the cells) and HER-2 negative disease (IHC 0 or 1+ and/or FISH negative, IHC 2+ and FISH negative) * Menopausal status * Patients must be post-menopausal as defined by one of the following criteria: * Prior bilateral oophorectomy * 12 months since LMP with no prior hysterectomy * Patients \> 55 years with prior hysterectomy * Patients \< 55 years of age and with a prior hysterectomy without oophorectomy, estradiol and FSH levels must be consistent with the patient being postmenopausal. * Premenopausal or perimenopausal women who do not meet the postmenopausal criteria above are also eligible, but are required to undergo ovarian suppression with an LHRH agonist. Ovarian suppression can be initiated any time prior to or on day 1 of protocol therapy and must continue throughout protocol therapy. * Performance status of 2 or better per SWOG criteria * No prior chemotherapy or endocrine therapy for the current cancer diagnosis. * If female of childbearing potential, pregnancy test is negative prior to initiation of ovarian suppression. * Patients must be informed of the investigational nature of the study, and must sign an informed consent in accordance with the institutional rules. * Oncotype Dx Recurrence Score \</= 25.
Exclusion criteria
* Patients with metastatic disease. * The presence of any other medical or psychiatric disorder that, in the opinion of the treating physician, would contraindicate the use of drugs in this protocol or place the subject at undue risk for treatment complications. * Premenopausal without ovarian suppression. * Pregnancy or lactation. * Patients with concomitant or previous malignancies within the last 5 years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix. * Patients with emotional limitations are excluded from study * Platelets less than 100 x 109 /L * Total bilirubin greater than 1.5 x ULRR * ALT or AST greater than 2.5 x ULRR * History of bleeding diathesis (i.e., disseminated intravascular coagulation \[DIC\], clotting factor deficiency) or long-term anticoagulant therapy (other than antiplatelet therapy). * History of hypersensitivity to active or inactive excipients of fulvestrant (i.e. castor oil or Mannitol). * Oncotype Dx Recurrence Score of \>25.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathologic Complete Response (PCR) Rate | 4 months | Pathologic complete response (PCR) rate with 4 months of neo-adjuvant combination endocrine therapy (Anastrazole and Fulvestrant). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arimidex + Faslodex Patients will have an Oncotype Dx performed and if the RS is \<25, they will receive Anastrazole and Fulvestrant for 16 weeks.
On day 28, subjects will be evaluated for side effects and a needle core biopsy (optional) will be obtained. Response evaluation will occur every 28 days. All treatment will continue for 4 months followed by breast surgery. After surgery, patients will be off study and will receive additional breast cancer therapy per their treating physician. Patients who develop progressive disease on protocol will be removed from the study and treated by their treating physician. The protocol will be closed after the last accrued patient has had surgery.
Fulvestrant: Fulvestrant IM on day 14 and on day 28 followed by day 28 of all subsequent cycles thereafter. Treatment will be continued for a total of 4 cycles.
Anastrazole: Anastrazole, 1mg by mouth every day of all 28 day cycles and continued for a total of 4 cycles | 42 |
| Total | 42 |
Baseline characteristics
| Characteristic | Arimidex + Faslodex |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 16 Participants |
| Age, Categorical Between 18 and 65 years | 26 Participants |
| Region of Enrollment United States | 42 participants |
| Sex: Female, Male Female | 42 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 42 |
| other Total, other adverse events | 40 / 42 |
| serious Total, serious adverse events | 4 / 42 |
Outcome results
Primary
Pathologic Complete Response (PCR) Rate
Pathologic complete response (PCR) rate with 4 months of neo-adjuvant combination endocrine therapy (Anastrazole and Fulvestrant).
Time frame: 4 months
Population: Number of participants with PCR after 4 cycles of Neoadjuvant Endocrine Therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arimidex + Faslodex | Pathologic Complete Response (PCR) Rate | 0 participants |