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S0226 Anastrozole With or Without Fulvestrant as First-Line Therapy in Postmenopausal Women With Metastatic Breast Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
National Cancer Institute (NCI)
NCIC Clinical Trials Group
Information provided by (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT00075764
First received: January 9, 2004
Last updated: October 5, 2012
Last verified: October 2012
History of Changes
  Purpose

RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using drugs such as anastrozole and fulvestrant may fight breast cancer by blocking the use of estrogen. It is not yet known whether anastrozole is more effective with or without fulvestrant in treating breast cancer.

PURPOSE: This randomized phase III trial is studying giving anastrozole together with fulvestrant to see how well it works compared to anastrozole alone as first-line therapy in treating postmenopausal women with metastatic breast cancer.


Condition Intervention Phase
Breast Cancer
 Drug: anastrozole
Drug: fulvestrant
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase III Randomized Trial of Anastrozole Versus Anastrozole and Fulvestrant as First Line Therapy for Post Menopausal Women With Metastatic Breast Cancer

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:
  • Time to tumor progression [ Time Frame: 13 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Clinical response rates [ Time Frame: 13 months ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 4 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 690
Study Start Date: April 2004
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I
Patients receive oral anastrozole once daily on days 1-28.
 Drug: anastrozole
Given orally
Experimental: Arm II
Patients receive oral anastrozole as in arm I. Patients also receive fulvestrant intramuscularly on days 1, 14, and 28 during course 1 and then on day 28 of the subsequent courses.
 Drug: anastrozole
Given orally
Drug: fulvestrant
Given intramuscularly

Detailed Description:

OBJECTIVES:

  • Compare the time to tumor progression in postmenopausal women with metastatic breast cancer treated with anastrozole with or without fulvestrant as first-line therapy.
  • Compare the clinical benefit (complete or partial response, confirmed or unconfirmed, or stable disease ≥ 24 weeks) and overall survival of patients treated with these regimens.
  • Compare adverse events in patients treated with these regimens.
  • Determine the prognostic significance of estrogen receptor positivity and HER2/neu status in patients treated with these regimens.
  • Determine parameters of estrogen and clinical pharmacology and estrogen levels in patients treated with these regimens.
  • Compare anastrozole plasma levels at 8, 16, and 24 weeks in patients treated with these regimens (closed as of 4/16/2009).
  • Compare estradiol serum levels at 8, 16, and 24 weeks in patients treated with these regimens (closed as of 4/16/2009).

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to prior adjuvant tamoxifen therapy (yes vs no). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive oral anastrozole once daily on days 1-28.
  • Arm II: Patients receive oral anastrozole as in arm I. Patients also receive fulvestrant intramuscularly on days 1, 14, and 28 during course 1 and then on day 28 of the subsequent courses.

In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients are followed for up to 4 years.

PROJECTED ACCRUAL: A total of 690 patients (345 per treatment arm) will be accrued for this study within 3 years.

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed breast cancer meeting 1 of the following criteria:

    • Metastatic disease (M1)
    • Multiple sites of new disease that is clinically obvious metastatic disease (e.g., multiple sites of new osseous disease)
  • Measurable or nonmeasurable disease
  • No known brain or CNS metastases

  • Hormone receptor status:

    • Estrogen-receptor positive* AND/OR
    • Progesterone-receptor positive* NOTE: *Positivity defined as estrogen binding of > 10 fmol/mg cytosol protein by ligand binding assay or positive by immunohistochemistry

PATIENT CHARACTERISTICS:

Age

  • Not specified

Sex

  • Female

Menopausal status

  • Postmenopausal, as defined by 1 of the following:

    • Prior bilateral oophorectomy
    • More than 12 months since last menstrual period with no prior hysterectomy
    • At least 55 years of age with prior hysterectomy
    • Under 55 years of age with a prior hysterectomy without oophorectomy and with estradiol and follicle-stimulating hormone levels consistent with menopause

Performance status

  • Zubrod 0-2

Life expectancy

  • Not specified

Hematopoietic

  • No bleeding diathesis (e.g., disseminated intravascular coagulation or clotting factor deficiency)

Hepatic

  • INR ≤ 1.6

Renal

  • Not specified

Other

  • HIV negative
  • No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer currently in complete remission

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No prior immunotherapy for recurrent or metastatic disease

Chemotherapy

  • No prior chemotherapy for recurrent or metastatic disease
  • More than 12 months since prior adjuvant or neoadjuvant chemotherapy
  • No concurrent chemotherapy for malignancy

Endocrine therapy

  • Prior adjuvant hormonal therapy allowed

  • At least 12 months since prior adjuvant luteinizing hormone-releasing hormone (LHRH) analogues

    • Menstrual periods must not have resumed since LHRH therapy
  • More than 12 months since prior adjuvant or neoadjuvant aromatase inhibitors (e.g., anastrozole, letrozole, or exemestane)
  • More than 12 months since prior fulvestrant
  • No prior hormonal therapy for recurrent or metastatic disease
  • No other concurrent hormonal therapy for malignancy
  • No concurrent hormone replacement therapy

Radiotherapy

  • Not specified

Surgery

  • Not specified

Other

  • No long-term anticoagulant therapy (except antiplatelet therapy)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00075764

  Show 426 Study Locations
Sponsors and Collaborators
Southwest Oncology Group
National Cancer Institute (NCI)
NCIC Clinical Trials Group
Investigators
Study Chair: Rita S. Mehta, MD Chao Family Comprehensive Cancer Center
Study Chair: Theodore A. Vandenberg, MD London Regional Cancer Program at London Health Sciences Centre
  More Information

Additional Information:
Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site
Featured trial article  This link exits the ClinicalTrials.gov site

No publications provided by Southwest Oncology Group

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT00075764     History of Changes
Other Study ID Numbers: CDR0000349337, U10CA032102, S0226, CAN-NCIC-MAC7
Study First Received: January 9, 2004
Last Updated: October 5, 2012
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by Southwest Oncology Group:
stage IV breast cancer
recurrent breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Fulvestrant
Anastrozole
Estradiol
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
 Estrogen Antagonists
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Estrogens
Hormones
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 19, 2013