We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

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:
ClinicalTrials.gov Identifier:
NCT00075764
First Posted: January 13, 2004
Last Update Posted: April 4, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
National Cancer Institute (NCI)
NCIC Clinical Trials Group
Information provided by (Responsible Party):
Southwest Oncology Group
January 9, 2004
January 13, 2004
October 26, 2016
April 4, 2017
April 4, 2017
April 2004
December 2012   (Final data collection date for primary outcome measure)
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.
Not Provided
Complete list of historical versions of study NCT00075764 on ClinicalTrials.gov Archive Site
  • 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
  • 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.
  • 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)
Not Provided
Not Provided
Not Provided
 
S0226 Anastrozole With or Without Fulvestrant as First-Line Therapy in Postmenopausal Women With Metastatic Breast Cancer
Phase III Randomized Trial of Anastrozole Versus Anastrozole and Fulvestrant as First Line Therapy for Post Menopausal Women With Metastatic Breast Cancer

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.

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.

Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Breast Cancer
  • Drug: anastrozole
    Given orally
  • Drug: fulvestrant
    Given intramuscularly
  • Active Comparator: Arm I
    Patients receive oral anastrozole once daily on days 1-28.
    Intervention: Drug: anastrozole
  • 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.
    Interventions:
    • Drug: anastrozole
    • Drug: fulvestrant
Mehta RS, Barlow WE, Albain KS, Vandenberg TA, Dakhil SR, Tirumali NR, Lew DL, Hayes DF, Gralow JR, Livingston RB, Hortobagyi GN. Combination anastrozole and fulvestrant in metastatic breast cancer. N Engl J Med. 2012 Aug 2;367(5):435-44. doi: 10.1056/NEJMoa1201622.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
695
October 2017
December 2012   (Final data collection date for primary outcome measure)

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)
Sexes Eligible for Study: Female
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Canada,   United States
 
 
NCT00075764
CDR0000349337
U10CA032102 ( U.S. NIH Grant/Contract )
S0226 ( Other Identifier: SWOG )
CAN-NCIC-MAC7 ( Other Identifier: NCIC-CTG )
Yes
Not Provided
Not Provided
Southwest Oncology Group
Southwest Oncology Group
  • National Cancer Institute (NCI)
  • NCIC Clinical Trials Group
Study Chair: Rita S. Mehta, MD Chao Family Comprehensive Cancer Center
Study Chair: Theodore A. Vandenberg, MD London Health Sciences Centre
Southwest Oncology Group
February 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP