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Trial record 1 of 1 for:    mehta AND fulvestrant
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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: February 15, 2017
Last verified: February 2017
  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: 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

Resource links provided by NLM:


Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:
  • 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:
  • 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)


Enrollment: 695
Study Start Date: April 2004
Estimated Study Completion Date: October 2017
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

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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
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: 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 Health Sciences Centre
  More Information

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 ( U.S. NIH Grant/Contract )
S0226 ( Other Identifier: SWOG )
CAN-NCIC-MAC7 ( Other Identifier: NCIC-CTG )
Study First Received: January 9, 2004
Results First Received: October 26, 2016
Last Updated: February 15, 2017

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

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

ClinicalTrials.gov processed this record on September 19, 2017