Bicalutamide in Treating Patients With Metastatic Breast Cancer

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Androgens can cause the growth of breast cancer cells. Antihormone therapy, such as bicalutamide, may stop the adrenal glands from making androgens. PURPOSE: This phase II trial is studying how well bicalutamide works in treating patients with metastatic breast cancer.

Detailed Description
-----------------
OBJECTIVES: Primary Determine the 6-month efficacy rate of bicalutamide as first-, second-, or third-line therapy in patients with androgen receptor-positive and estrogen receptor- and progesterone receptor-negative metastatic breast cancer. Secondary Determine the 6-month progression-free survival of patients treated with this drug. Evaluate the safety of this drug in these patients. Evaluate changes in estradiol, total and free testosterone, and sex-hormone binding globulin in response to androgen blockade in patients treated with this drug. Evaluate tissue, including cytokeratins 5/6 and 17, SPDEF, ALCAM, ERBB2, FGFR4, and prostate-specific antigen (PSA), using immunohistochemical analysis in patients treated with this drug. OUTLINE: This is a open-label study. Patients receive oral bicalutamide once daily for 4 weeks. Treatment repeats every 4 weeks for 6 months in the absence of disease progression or unacceptable toxicity. Patients achieving complete response, partial response, or stable disease may continue to receive bicalutamide as above at the discretion of the investigator. Patients undergo blood and tissue sample collection for correlative studies. Samples are analyzed for hormonal levels, including estradiol, total testosterone, free testosterone, and sex-hormone binding globulin, and proteins, including ALCAM, SPEDF, and CK 5/6, by immunohistochemical analysis at baseline, after course 1, and at the end of the study. After completion of study treatment, patients are followed every 3 months. PROJECTED ACCRUAL: A total of 28 patients will be accrued for this study.

Official Title
-----------------
Bicalutamide for the Treatment of Androgen Receptor Positive (AR(+)), Estrogen Receptor Negative, Progesterone Receptor Negative (ER(-)/PR(-)) Metastatic Breast Cancer Patients: A Phase II Feasibility Study

Conditions
-----------------
Breast Cancer

Intervention / Treatment
-----------------
* Drug: bicalutamide
* Other: diagnostic laboratory biomarker analysis
* Other: immunohistochemistry staining method


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the breast Stage IV disease Measurable or non-measurable disease Patients with HER2/neu-positive disease must have received prior trastuzumab (Herceptin®) No active brain metastases or leptomeningeal disease History of brain metastases allowed provided lesions are stable for at least 3 months as documented by head CT scan or MRI of the brain Hormone receptor status: Estrogen receptor- and progesterone receptor-negative* Androgen receptor-positive* NOTE: *Samples are considered positive if greater than 10% of cell nuclei are immunoreactive PATIENT CHARACTERISTICS: Male or female Menopausal status not specified ECOG performance status 0-1 Absolute neutrophil count ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Hemoglobin ≥ 9 g/dL AST and ALT ≤ 2.5 times upper limit of normal (ULN) Bilirubin ≤ 1.5 times ULN Alkaline phosphatase ≤ 2.5 times ULN (unless bone metastases are present in the absence of liver metastases) Creatinine ≤ 1.5 mg/dL Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No serious medical or psychiatric illness No serious active infection No other malignancy within the past 5 years except nonmelanoma skin cancer No hypersensitivity reaction to bicalutamide or any of the tablet's components PRIOR CONCURRENT THERAPY: At least 2 weeks since prior cytotoxic chemotherapy and recovered At least 3 weeks since prior investigational drugs At least 4 weeks since prior major surgery and recovered Prior neoadjuvant or adjuvant chemotherapy allowed Any number of chemotherapy regimens are allowed for metastatic disease Prior hormonal therapy allowed No concurrent chemotherapy, other hormonal therapy, immunotherapy, or biological therapy No concurrent trastuzumab (Herceptin®) No concurrent enrollment in another clinical trial in which investigational procedures are performed or investigational therapies are administered

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: bicalutamide<br>This is a multicenter, open-label, phase II study to evaluate the antitumor activity and safety of bicalutamide administered orally daily to patients with ER(-)/PR(-)/AR(+) metastatic breast cancer. Eligible patients who have consented to trial participation will receive bicalutamide at a dose of 150mg PO daily. | Drug: bicalutamide<br> <br> Other: diagnostic laboratory biomarker analysis<br> <br> Other: immunohistochemistry staining method<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6-month Response Rate (Complete Response, Partial Response, and Stable Disease) | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Count of Participants With Progression-free Survival | Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions | 1 year | 
| Number of Participants Evaluated for Toxicity | Toxicity measured by CTCAE v3.0 | 1 year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
stage IV breast cancer, recurrent breast cancer, male breast cancer