Purpose and Objectives
The primary objective of this study is to determine if ER-targeted therapy, ARIMIDEX and FASLODEX, used in combination is superior to ARMIDEX alone in hormone receptor positive breast cancer.
Primary study objective 1. To determine the efficacy of primary breast cancer, as measured by decrease in proliferation (KI67), to the combination of ARIMIDEX, and FASLODEX at high dose
Secondary study objectives 1. To study molecular changes in response to treatment. 2. To correlate changes in Ki67 with clinical response 3. To determine the pathologic response rate. 4. To assess the tolerability and safety of the combination regimen.
This is a phase II randomized multi-center study. As indicated in the study design schema found in the protocol document attached to Section S, patients will be initially randomized to receive ARIMIDEX, or ARIMIDEX+FASLODEX (high dose) for 16 weeks (112 days). A computer-generated randomization scheme will be generated by the study statistician at the Breast Center, Baylor College of Medicine. A 1:1 randomization scheme using permuted blocks will be employed. Randomization will be centralized at the Breast Center, Baylor College of Medicine and accomplished via access to a secure web-based procedure that is currently being implemented in our other multi-center clinical trials. Enrollment, eligibility, and randomization information will be stored in an Oracle database on the Breast Center's Sun server and will be accessible only through secure web-based applications. Communication with the pharmacy will be handled by email which will contain only patient identification number and initials and by FAX or hardcopy. The hardcopy will be used by physicians to send to the pharmacy a signed computer-generated pharmacy order to legally dispense study drug.
Within 30 days prior to randomization subjects will sign the study consent form, and have a history and physical exam, including all concurrent medications. Blood will be drawn for CBC, platelets, serum chemistries, BUN, creatinine, and liver function tests. If necessary to determine menopausal status FSH, LH and serum estradiol will be obtained. An EKG, CXR PA and lateral will be performed and a bilateral mammogram and US of primary breast cancer will be done within 90 days of randomization. Subjects will then be randomized to receive either ARIMIDEX 1 mg po q day (Group A), or ARIMIDEX 1 mg po q day and FASLODEX 500 mg IM, day 1, day 14, day 28 and thereafter once every 28 days (Group B). Study medications will be dispensed within 60 days of randomization. On day 28, subjects will be evaluated for side effects and a second breast core biopsy will be obtained. Evaluation for tumor response and tolerability of the regimen will be evaluated every 28 days in outpatient clinic visits. ALL treatment will continue until day 112 when patients with a clinical response or stable disease will receive appropriate surgical resection. If the tumor is unresectable on day 112, a core needle biopsy will be done. The surgical specimen will be obtained for further molecular analysis. 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 taken off study and offered alternative treatment. All patients will have a safety follow-up 1 month after the surgery (or the alternative core biopsy).
Treatment will be administered on outpatient basis. After the baseline breast biopsy, patients will be randomized to receive ARIMIDEX 1mg po q day (group A), or ARIMIDEX 1mg po q day with FASLODEX 500 mg day 1, day 14, day 28, and thereafter every 28 days (Group B). After 28 days a second biopsy will be obtained in all patients. All patients will continue on the same randomized treatment for the total duration of the study of 112 days till the day before surgery. No investigational or commercial agents or therapies other than those described below may be administered with the intent to treat the patient's malignancy.
Study Visit Procedures: Pre-Study Procedures will include the following: informed consent, breast biopsy, demographics, medical history, concurrent medication list, physical exam, blood draw, bidimensional tumor measurement, bilateral mammogram, primary breast ultrasound and chest x-ray.
Day 1 procedures will include the following: study drug administration, clinic visit.
Day 14 procedures will include the following (group B only) study drug injection and clinic visit.
Day 28 procedures will include the following (group B only) study drug injection. Both group A and B, breast biopsy, concurrent medication list, physical exam, blood draw, clinic visit, adverse events evaluation, bidimensional tumor measurement.
Day 56 procedures will include the following (group B only) study drug injection. Both group A and B, concurrent medication list, physical exam, blood draw, adverse events evaluation, clinic visit and bidimensional tumor measurement.
Day 84 procedures include (group B only) study drug injection. Both group A and B, concurrent medication list, physical exam, blood draw, adverse event evaluation, clinic visit and bidimensional tumor measurement.
Day 112 procedures include study drug administration, concurrent medication list, physical exam, blood draw, adverse events evaluation, bidimensional tumor measurement, bilateral mammogram, primary breast ultrasound and tumor resection.
Day 140 procedures include blood draw, clinic visit and safety evaluation for adverse events.
Duration of Therapy In the absence of treatment delays due to adverse events, treatment will continue for 4 months or until one of the following criteria applies: Disease progression, Intercurrent illness that prevents further administration of treatment, Unacceptable adverse events(s), Patient decides to withdraw from the study, or General or specific changes in the patient's condition render the patient unacceptable for further treatment in the judgment of the investigator.
This protocol will close 6 months after the last patient is enrolled. Patients will receive study medications from day 0 until day 111, which is the day before their planned surgery. On day 140, patients will have a safety follow up visit and to determine the need for further treatment after surgery.
Breast Core Biopsy All subjects will have a breast tumor core biopsy at the beginning of the study, and a second biopsy after 2 weeks. Core needle biopsies are planned because they will provide sufficient histologically evaluable tissue for the assays proposed in this study.
