Bicalutamide in Treating Patients With Metastatic Breast Cancer

• Sponsor: Memorial Sloan Kettering Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00468715
• Collaborator: National Cancer Institute (NCI) (NIH), AstraZeneca (Industry)
• Enrollment: 28
• Locations: 8
• Arm: 1
• Actual Duration (Months): 171.1
• Patients Per Site: 3.5
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: bicalutamide; Other: diagnostic laboratory biomarker analysis; Other: immunohistochemistry staining method	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 28 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Mar 23, 2007
• Actual Primary Completion Date: Jun 24, 2021
• Actual Study Completion Date: Jun 24, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: bicalutamide; Other: diagnostic laboratory biomarker analysis; Other: immunohistochemistry staining method

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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

2. Number of Participants Evaluated for Toxicity [1 year]

   Toxicity measured by CTCAE v3.0

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California	United States	94115
2	Lombardi Comprehensive Cancer Center at Georgetown University Medical Center	Washington	District of Columbia	United States	20007
3	Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
4	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
5	Ralph Lauren Center for Cancer Care and Prevention	New York	New York	United States	10035
6	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
7	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina	United States	27599-7295
8	Duke Cancer Institute	Durham	North Carolina	United States	27710

Sponsors and Collaborators

• Memorial Sloan Kettering Cancer Center
• National Cancer Institute (NCI)
• AstraZeneca

Investigators

• Principal Investigator: Tiffany A. Traina, MD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 22, 2012

More Information

Additional Information:

• Memorial Sloan Kettering Cancer Center

Publications

None provided.

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT00468715
• Other Study ID Numbers: 07-022; MSKCC-07022
• First Posted: May 3, 2007
• Last Update Posted: Aug 3, 2022
• Last Verified: Jun 1, 2021

• Keywords provided by Memorial Sloan Kettering Cancer Center: stage IV breast cancer; recurrent breast cancer; male breast cancer
• Additional relevant MeSH terms: Breast Neoplasms; Bicalutamide

Study Results

Participant Flow

Arm/Group Title	Bicalutamide
Arm/Group Description	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
Period Title: Overall Study
STARTED	28
COMPLETED	28
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Bicalutamide
Arm/Group Description	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
Overall Participants	28
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	54
Sex: Female, Male (Count of Participants)
Female	28 100%
Male	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 3.6%
Not Hispanic or Latino	1 3.6%
Unknown or Not Reported	26 92.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	5 17.9%
White	22 78.6%
More than one race	0 0%
Unknown or Not Reported	1 3.6%
Region of Enrollment (Count of Participants)
United States	28 100%

Outcome Measures

1. Primary Outcome

Title	6-month Response Rate (Complete Response, Partial Response, and Stable Disease)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bicalutamide
Arm/Group Description	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
Measure Participants	28
Stable Disease	9 32.1%
Progression of Disease	15 53.6%
Not Entered	4 14.3%

2. Secondary Outcome

Title	Count of Participants With Progression-free Survival
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bicalutamide
Arm/Group Description	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
Measure Participants	28
Participants who progressed	22 78.6%
Participants who did not progress	6 21.4%

3. Secondary Outcome

Title	Number of Participants Evaluated for Toxicity
Description	Toxicity measured by CTCAE v3.0
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bicalutamide
Arm/Group Description	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
Measure Participants	28
Count of Participants [Participants]	28 100%

Adverse Events

Time Frame	1 year
Arm/Group Title	Bicalutamide
Arm/Group Description	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
All Cause Mortality
	Bicalutamide
	Affected / at Risk (%)	# Events
Total	14/28 (50%)
Serious Adverse Events
	Bicalutamide
	Affected / at Risk (%)	# Events
Total	4/28 (14.3%)
Blood and lymphatic system disorders
Blood/Bone Marrow, other	1/28 (3.6%)
Hemoglobin	4/28 (14.3%)
Gastrointestinal disorders
Colitis, infection	2/28 (7.1%)
Diarrhea	3/28 (10.7%)
Nausea	2/28 (7.1%)
Pain - abdomen NOS	1/28 (3.6%)
Vomiting	1/28 (3.6%)
General disorders
Fatigue	1/28 (3.6%)
Fever (in the absence of neutropenia)	1/28 (3.6%)
Investigations
Bilirubin (hyperbilirubinemia)	1/28 (3.6%)
Lymphopenia	1/28 (3.6%)
Platelets	1/28 (3.6%)
Metabolism and nutrition disorders
Albumin, low (hypoalbuminemia)	3/28 (10.7%)
Anorexia	2/28 (7.1%)
Dehydration	2/28 (7.1%)
Glucose, high (hyperglycemia)	4/28 (14.3%)
Magnesium, low (hypomagnesemia)	4/28 (14.3%)
Phospate, low (hypophosphatemia)	4/28 (14.3%)
Potassium, high (hyperkalemia)	1/28 (3.6%)
Potassium, low (hypokalemia)	4/28 (14.3%)
Musculoskeletal and connective tissue disorders
Pain - back	1/28 (3.6%)
Nervous system disorders
CNS cerebrovascular ischemia	1/28 (3.6%)
Psychiatric disorders
Mood alteration - Depression	1/28 (3.6%)
Respiratory, thoracic and mediastinal disorders
Cough	1/28 (3.6%)
Dyspnea (shortness of breath)	1/28 (3.6%)
Other (Not Including Serious) Adverse Events
	Bicalutamide
	Affected / at Risk (%)	# Events
Total	28/28 (100%)
Blood and lymphatic system disorders
Hemoglobin	6/28 (21.4%)
Eye disorders
Ocular/visual - other	2/28 (7.1%)
Gastrointestinal disorders
Constipation	5/28 (17.9%)
Nausea	4/28 (14.3%)
Diarrhea	3/28 (10.7%)
Heartburn/dyspepsia	3/28 (10.7%)
Pain - Abdomen NOS	2/28 (7.1%)
General disorders
Fatigue	9/28 (32.1%)
Edema, limb	8/28 (28.6%)
Pain - other (specify)	2/28 (7.1%)
Investigations
AST, SGOT	10/28 (35.7%)
ALT, SGPT	8/28 (28.6%)
Alkaline Phosphatase	5/28 (17.9%)
Leukocytes (total WBC)	5/28 (17.9%)
Bilirubin (hyperbilirubinemia)	4/28 (14.3%)
Platelets	3/28 (10.7%)
Creatinine	2/28 (7.1%)
Metabolism and nutrition disorders
Glucose, high (hyperglycemia)	6/28 (21.4%)
Anorexia	4/28 (14.3%)
Albumin, low (hypoalbuminemia)	2/28 (7.1%)
Glucose, low (hypoglycemia)	2/28 (7.1%)
Musculoskeletal and connective tissue disorders
Pain - Extremity-limb	3/28 (10.7%)
Pain - Back	2/28 (7.1%)
Pain - Bone	2/28 (7.1%)
Nervous system disorders
Neuropathy, sensory	4/28 (14.3%)
Psychiatric disorders
Mood alteration - Anxiety	2/28 (7.1%)
Mood alteration - Depression	2/28 (7.1%)
Reproductive system and breast disorders
Pain - breast	3/28 (10.7%)
Vaginal dryness	2/28 (7.1%)
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)	3/28 (10.7%)
Cough	2/28 (7.1%)
Skin and subcutaneous tissue disorders
Dermatology/Skin, other	3/28 (10.7%)
Dry skin	2/28 (7.1%)
Vascular disorders
Hot flashes/flushes	7/28 (25%)
Hypertension	2/28 (7.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.