Breast Cancer
Conditions
Keywords
stage IV breast cancer, recurrent breast cancer, male breast cancer
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.
Interventions
Sponsors
Study design
Eligibility
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 6-month Response Rate (Complete Response, Partial Response, and Stable Disease) | 6 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Count of Participants With Progression-free Survival | 1 year | 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 |
| Number of Participants Evaluated for Toxicity | 1 year | Toxicity measured by CTCAE v3.0 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bicalutamide 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.
bicalutamide
diagnostic laboratory biomarker analysis
immunohistochemistry staining method | 28 |
| Total | 28 |
Baseline characteristics
| Characteristic | Bicalutamide |
|---|---|
| Age, Continuous | 54 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 26 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 22 Participants |
| Region of Enrollment United States | 28 Participants |
| Sex: Female, Male Female | 28 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 14 / 28 |
| other Total, other adverse events | 28 / 28 |
| serious Total, serious adverse events | 4 / 28 |
Outcome results
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.
Time frame: 6 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Bicalutamide | 6-month Response Rate (Complete Response, Partial Response, and Stable Disease) | Stable Disease | 9 Participants |
| Bicalutamide | 6-month Response Rate (Complete Response, Partial Response, and Stable Disease) | Progression of Disease | 15 Participants |
| Bicalutamide | 6-month Response Rate (Complete Response, Partial Response, and Stable Disease) | Not Entered | 4 Participants |
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
Time frame: 1 year
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Bicalutamide | Count of Participants With Progression-free Survival | Participants who progressed | 22 Participants |
| Bicalutamide | Count of Participants With Progression-free Survival | Participants who did not progress | 6 Participants |
Number of Participants Evaluated for Toxicity
Toxicity measured by CTCAE v3.0
Time frame: 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Bicalutamide | Number of Participants Evaluated for Toxicity | 28 Participants |