Exemestane in Treating Postmenopausal Women With Stage IV Breast Cancer

Phase 2

Completed

Conditions: Breast Cancer

Interventions: Drug: exemestane
Other: laboratory biomarker analysis
Procedure: quality-of-life assessment
Other: immunohistochemistry staining method

Registration Number: NCT00810797

Lead Sponsor: City of Hope Medical Center

Brief Summary: RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using exemestane may fight breast cancer by lowering the amount of estrogen the body makes.

PURPOSE: This phase II trial is studying how well exemestane works in treating postmenopausal women with stage IV breast cancer.

Detailed Description: PRIMARY OBJECTIVES:

I. Progression-free survival at 4 months, as measured by Response Evaluation Criteria in Solid Tumors (RECIST).

SECONDARY OBJECTIVES:

I. Objective response rate (complete response \[CR\] and partial response \[PR\]).

II. Clinical benefit (CR, PR, and stable disease \>= 6 months).

III. Assessment of toxicity.

IV. Assessment of compliance with medication adherence.

V. Assessment of quality of life.

VI. Assessment of bone health.

TERTIARY OBJECTIVES:

I. Serial measurements of serum estradiol, estrone, and estrone sulfate.

II. To investigate treatment resistance (e.g., expression of amphiregulin, epidermal growth factor receptor \[EGFR\]), using molecular and immunohistochemical analyses of blood and tumor samples of pre- and post- (when available) treatment tissues. Microarray analyses to quantitate the expression of specific estrogen-responsive genes (e.g. thyroid transcription factor 1 \[TTF1\] and PDZK1) will also be performed.

OUTLINE: Patients receive exemestane orally (PO) once daily (QD) on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed periodically for 1 year.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 36

Inclusion Criteria

Histologically or cytologically confirmed metastatic carcinoma of the breast
Hormone receptor (estrogen receptor [ER] and/or progesterone receptor [PR]) positive disease (defined as: ER and/or PR positivity as >= 5% staining), as confirmed by immunohistochemistry (IHC) based on primary breast tissue or metastatic tissue
Postmenopausal, as defined by any of the following:
Natural menopause, with at least 1 year since last menses
Chemotherapy-induced menopause with at least 1 year from last menses and serum luteinizing hormone (LH)/follicle-stimulating hormone (FSH) and estradiol levels within the postmenopausal range
History of surgical or radiation-induced ovarian ablation
For women =< 56 years old and with a history of hysterectomy but at least one ovary intact, serum LH/FSH and estradiol levels must be within the postmenopausal range
Postmenopausal women with disease recurrence while receiving either tamoxifen or a non-steroidal aromatase inhibitor (AI) as adjuvant therapy (as long as adjuvant hormonal therapy was taken for 6 months before disease progression) or with disease recurrence following the discontinuation/completion of adjuvant hormonal therapy
Postmenopausal women with disease progression following either 0, 1 or 2 prior hormonal therapies for metastatic breast cancer, as long as the subject has had no prior exposure to exemestane (EXE)
Measurable or non-measurable (but evaluable) disease, as defined by RECIST criteria
Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
Neutrophil count >= 1.5 X 10^9 cells/L
Platelet count >= 100 X 10^9 cells/L
Serum creatinine =< 1.5 times upper limit of normal (ULN)
Total serum bilirubin =< 1.5 times ULN
Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) levels =< 2.5 x ULN in patients without liver metastases or =< 5 times ULN in patients with liver metastases
Alkaline phosphatase =< 2.5 times the ULN for patients without bone or liver metastases
Subjects must have an estimated life expectancy of greater than 6 months

Exclusion Criteria

Prior exposure to EXE, whether in the adjuvant or metastatic setting
Prior history of any other cancer with the exception of non-melanoma skin cancer and treated in situ carcinoma of the cervix
Active or symptomatic central nervous system (CNS) metastasis (stable or treated brain metastasis allowed but patients must be off decadron, if given for CNS disease)
Hormone-receptor negative or unknown breast cancer
More than two prior chemotherapy regimen for treatment of metastatic disease (any prior chemotherapy given in the adjuvant setting is permitted)
Administration of any other anti-cancer therapy within 2 weeks of initiating study treatment; use of bisphosphonates, however, are permitted for patients with known bone metastases
Treatment with any other concurrent investigational agent or anti-tumor drug (chemotherapy, antibody therapy or other biologic agents), will not be permitted
Subjects who have had no prior exposure to endocrine therapy
Any uncontrolled medical co-morbidity or psychiatric disorder which interferes with the ability to provide informed consent or comply with study procedures

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (exemestane)	laboratory biomarker analysis	Patients receive oral exemestane once daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Treatment (exemestane)	quality-of-life assessment	Patients receive oral exemestane once daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Treatment (exemestane)	immunohistochemistry staining method	Patients receive oral exemestane once daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Treatment (exemestane)	exemestane	Patients receive oral exemestane once daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Progression-free Survival	Until disease progression of death from any cause, up to 3 years	Estimated using the product-limit method of Kaplan and Meier. 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.

Secondary Outcome Measures

Name	Time	Method
Overall Response Rate	Until disease progression or off treatment, assessed up to 1 year	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

Trial Locations

Locations (2): South Pasadena Cancer Center
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South Pasadena, California, United States
City of Hope Medical Center
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Duarte, California, United States