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

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ClinicalTrials.gov Identifier: NCT00075764
Recruitment Status : Completed
First Posted : January 13, 2004
Results First Posted : April 4, 2017
Last Update Posted : January 13, 2021
Sponsor:
Collaborators:
National Cancer Institute (NCI)
NCIC Clinical Trials Group
Information provided by (Responsible Party):
SWOG Cancer Research Network

Study Description
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Brief Summary:

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 or disease Intervention/treatment Phase
Breast Cancer Drug: anastrozole Drug: fulvestrant Phase 3

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 695 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Study Start Date : April 2004
Actual Primary Completion Date : December 2012
Actual Study Completion Date : October 1, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arms and Interventions
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Arm Intervention/treatment
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


Outcome Measures
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Primary Outcome Measures :
  1. Time to Tumor Progression [ Time Frame: Every 4 weeks while on treatment. Then every 3 months until progression, then six months for two years then annually until four years or until death, which ever occurs first. ]
    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 measurable lesions over the smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline. Unequivocal progression of non-measurable disease in the opinion of the treating physician. Appearance of any new lesion/site. Death due to disease without prior documentation of progression and without symptomatic deterioration. From date of randomization to time of first documentation of progression, symptomatic deterioration or death due to any cause. Patients last known to be alive and progression free are considered at last date of contact.


Secondary Outcome Measures :
  1. Clinical Benefit (CR, PR, Confirmed or Unconfirmed, or Stable Disease >= 24 Weeks). [ Time Frame: Every 4 weeks while on treatment. Then every 3 months until progression, then six months for two years then annually until four years or until death, which ever occurs first. ]
    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; Stable, Does not qualify for CR, PR, Progression or Symptomatic Deterioration. Clinical Benefit = CR + PR + Stable >= 24 weeks

  2. Overall Survival [ Time Frame: Every 4 weeks while on treatment. Then every 3 months until progression, then six months for two years then annually until four years or until death, which ever occurs first. ]
    From date of randomization to date of death due to any cause. Patients last known to be alive are censored at last date of contact.

  3. Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs [ Time Frame: Patients were assessed for adverse events after each cycle (1 cycle = 28 days) while on treatment. ]
    Adverse Events (AEs) are reported by CTCAE version 3.0 terminology. For each patient, worst grade of each event type is reported. Grade3 (Severe), Grade4 (Life-threatening), Grade 5 (Fatal)


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes 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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00075764


Locations
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Sponsors and Collaborators
SWOG Cancer Research Network
National Cancer Institute (NCI)
NCIC Clinical Trials Group
Investigators
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Study Chair: Rita S. Mehta, MD Chao Family Comprehensive Cancer Center
Study Chair: Theodore A. Vandenberg, MD London Health Sciences Centre
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: SWOG Cancer Research Network
ClinicalTrials.gov Identifier: NCT00075764    
Other Study ID Numbers: CDR0000349337
U10CA032102 ( U.S. NIH Grant/Contract )
S0226 ( Other Identifier: SWOG )
CAN-NCIC-MAC7 ( Other Identifier: NCIC-CTG )
First Posted: January 13, 2004    Key Record Dates
Results First Posted: April 4, 2017
Last Update Posted: January 13, 2021
Last Verified: January 2021
Keywords provided by SWOG Cancer Research Network:
stage IV breast cancer
recurrent breast cancer
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Fulvestrant
Anastrozole
Antineoplastic Agents, Hormonal
Antineoplastic Agents
 Estrogen Receptor Antagonists
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action