Bicalutamide in Treating Patients With Metastatic Breast Cancer

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

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Other: diagnostic laboratory biomarker analysis; Other: immunohistochemistry staining method; Drug: bicalutamide

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 Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94115
      • UCSF Helen Diller Family Comprehensive Cancer Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10035
      • Ralph Lauren Center for Cancer Care and Prevention
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7295
      • Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
    • Durham, North Carolina, United States, 27710
      • Duke Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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.	Other: diagnostic laboratory biomarker analysis; Other: immunohistochemistry staining method; Drug: bicalutamide

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

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: National Cancer Institute (NCI); AstraZeneca
• Investigators: Principal Investigator: Tiffany A. Traina, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2007
• Primary Completion (Actual): June 24, 2021
• Study Completion (Actual): June 24, 2021

Study Registration Dates

• First Submitted: May 2, 2007
• First Submitted That Met QC Criteria: May 2, 2007
• First Posted (Estimate): May 3, 2007

Study Record Updates

• Last Update Posted (Actual): August 3, 2022
• Last Update Submitted That Met QC Criteria: July 8, 2022
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: stage IV breast cancer; recurrent breast cancer; male breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Androgen Antagonists; Bicalutamide
• Other Study ID Numbers: 07-022; MSKCC-07022