Exemestane in Treating Postmenopausal Women With Stage IV Breast Cancer

Intermittent Exemestane Therapy for Metastatic Breast Cancer

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Other: immunohistochemistry staining method; Drug: exemestane; Other: laboratory biomarker analysis; Procedure: quality-of-life assessment

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.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010-3000
      • City of Hope Medical Center
    • South Pasadena, California, United States, 91030
      • South Pasadena Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 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: Treatment (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.	Other: immunohistochemistry staining method; Correlative studies; Other Names: immunohistochemistry; Drug: exemestane; Given orally; Other: laboratory biomarker analysis; One year after completion of study treatment; Procedure: quality-of-life assessment; One year after completion of study treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival	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.	Until disease progression of death from any cause, up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate	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	Until disease progression or off treatment, assessed up to 1 year

Collaborators and Investigators

• Sponsor: City of Hope Medical Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: George Somlo, MD, City of Hope Medical Center

Study record dates

Study Major Dates

• Study Start: December 2, 2008
• Primary Completion (Actual): June 26, 2019
• Study Completion (Actual): June 26, 2019

Study Registration Dates

• First Submitted: December 17, 2008
• First Submitted That Met QC Criteria: December 17, 2008
• First Posted (Estimate): December 18, 2008

Study Record Updates

• Last Update Posted (Actual): October 19, 2020
• Last Update Submitted That Met QC Criteria: September 23, 2020
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: stage IV breast cancer; recurrent breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Exemestane
• Other Study ID Numbers: 08063; P30CA033572 (U.S. NIH Grant/Contract); CHNMC-08063; CDR0000629864 (Registry Identifier: NCI PDQ); NCI-2010-00761 (Registry Identifier: NCI CTRP)