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Exemestane in Treating Postmenopausal Women With Stage IV Breast Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT00810797
First received: December 17, 2008
Last updated: September 5, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Drug: exemestane
Other: laboratory biomarker analysis
Procedure: quality-of-life assessment
Other: immunohistochemistry staining method
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Intermittent Exemestane Therapy for Metastatic Breast Cancer

Resource links provided by NLM:


Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:
  • Progression-free survival measured by RECIST [ Time Frame: 4 months after the start of treatment ] [ Designated as safety issue: No ]
    Reported using the method of Kaplan-Meier.


Secondary Outcome Measures:
  • Objective response [ Time Frame: Assessed up to 1 year ] [ Designated as safety issue: No ]
  • Toxicity as assessed by NCI CTCAE version 3.0 [ Time Frame: Assessed up to 1 year ] [ Designated as safety issue: Yes ]
  • Compliance with medication adherence [ Time Frame: Assessed up to 1 year ] [ Designated as safety issue: No ]
    Patients will be supplied with a calendar of the treatment schedule and will be instructed to track their daily consumption of exemestane at home.

  • Quality of life as assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 [ Time Frame: On day 1 of each treatment course ] [ Designated as safety issue: No ]
    This instrument consists of a 30-item, cancer-specific tool which encompasses measures of physical, emotional, cognitive, and social well being, in addition to measures of symptoms and overall quality of life.

  • Bone health [ Time Frame: 21 days after the start of the last course of treatment ] [ Designated as safety issue: No ]
  • Serum hormone levels [ Time Frame: 21 days after the start of the last course of treatment ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Expression of amphiregulin and EGFR using molecular and immunohistochemical analyses of blood and tumor samples [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • Expression of specific estrogen-responsive genes (TTF1 and PDZk1) [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 36
Study Start Date: October 2008
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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
Other: immunohistochemistry staining method
Correlative studies
Other Name: immunohistochemistry

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00810797

Locations
United States, California
City of Hope Medical Center
Duarte, California, United States, 91010-3000
South Pasadena Cancer Center
South Pasadena, California, United States, 91030
Sponsors and Collaborators
City of Hope Medical Center
Investigators
Principal Investigator: George Somlo, MD City of Hope Medical Center
  More Information

Additional Information:
No publications provided

Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT00810797     History of Changes
Other Study ID Numbers: 08063, P30CA033572, CHNMC-08063, CDR0000629864, NCI-2010-00761
Study First Received: December 17, 2008
Last Updated: September 5, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by City of Hope Medical Center:
recurrent breast cancer
stage IV breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Exemestane
Antineoplastic Agents
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 23, 2014