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Fulvestrant With or Without Anastrozole or Exemestane Alone in Treating Postmenopausal Women With Locally Advanced or Metastatic Breast Cancer
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), April 2008
Sponsored by: Institute of Cancer Research, United Kingdom
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00253422
  Purpose

RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using fulvestrant, anastrozole, or exemestane may fight breast cancer by blocking the use of estrogen by the tumor cells or by lowering the amount of estrogen the body makes. It is not yet known whether giving fulvestrant together with anastrozole is more effective than giving fulvestrant together with a placebo or exemestane alone in treating breast cancer.

PURPOSE: This randomized phase III trial is studying fulvestrant and anastrozole to see how well they work compared to fulvestrant and a placebo or exemestane alone in treating postmenopausal women with locally advanced or metastatic breast cancer.


Condition Intervention Phase
Breast Cancer
Drug: anastrozole
Drug: exemestane
Drug: fulvestrant
Phase III

Genetics Home Reference related topics: breast cancer
MedlinePlus related topics: Breast Cancer Cancer
Drug Information available for: Anastrozole Ici 182780 Exemestane
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Double-Blind, Placebo Control
Official Title: A Partially-Blind Phase III Randomized Trial of Fulvestrant (Faslodex™) With or Without Concomitant Anastrozole (Arimidex™) Compared With Exemestane in Postmenopausal Women With ER+ve Locally Advanced/Metastatic Breast Cancer Following Progression on Non-Steroidal Aromatase Inhibitors

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Progression-free survival [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Objective complete response (CR) and partial response (PR) rate [ Designated as safety issue: No ]
  • Duration of response [ Designated as safety issue: No ]
  • Clinical benefit (i.e., 6-month CR, PR, and stable disease) rate [ Designated as safety issue: No ]
  • Duration of clinical benefit [ Designated as safety issue: No ]
  • Time to treatment failure [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Tolerability [ Designated as safety issue: Yes ]

Estimated Enrollment: 750
Study Start Date: March 2004
Detailed Description:

OBJECTIVES:

Primary

  • Compare progression-free survival of postmenopausal women with estrogen receptor- and/or progesterone receptor-positive, locally advanced or metastatic breast cancer that relapsed or progressed during prior treatment with nonsteroidal aromatase inhibitors treated with fulvestrant with vs without anastrozole vs exemestane alone.

Secondary

  • Compare the objective complete response (CR) and partial response (PR) rate and duration of response in patients treated with these regimens.
  • Compare the clinical benefit (i.e., 6-month CR, PR, and stable disease) rate and duration of clinical benefit in patients treated with these regimens.
  • Compare time to treatment failure in patients treated with these regimens.
  • Compare the overall survival of patients treated with these regimens.
  • Compare the tolerability of these regimens in these patients.

OUTLINE: This is a randomized, partially double-blind and placebo-controlled, multicenter study. Patients are stratified according to the setting in which prior nonsteroidal aromatase-inhibitor therapy was given (adjuvant therapy vs first-line therapy) and participating center. Patients are randomized to 1 of 3 treatment arms.

  • Arm I (fulvestrant and anastrozole): Patients receive fulvestrant intramuscularly (IM) on days 1, 15, and 29 and then once monthly. Patients receive oral anastrozole once daily.
  • Arm II (fulvestrant and placebo): Patients receive fulvestrant as in arm I and oral placebo once daily.
  • Arm III (exemestane alone): Patients receive oral exemestane once daily. In all arms, treatment repeats every month in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for survival.

PROJECTED ACCRUAL: A total of 750 patients (250 per treatment arm) will be accrued for this study.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed adenocarcinoma of the breast

    • Locally advanced or metastatic disease
  • Metastatic disease must be measurable or evaluable

    • Patients with bone only metastases are eligible provided there is an evaluable site of bone metastasis that can be followed by x-ray, MRI, or CT scan
  • Relapsed or progressed during prior treatment with single-agent nonsteroidal aromatase inhibitor (NSAI)*, meeting either of the following criteria:

    • NSAI given as adjuvant therapy that lasted ≥ 12 months
    • Achieved an objective complete response, partial response, or stable disease that lasted ≥ 6 months after prior first-line therapy with NSAI for locally advanced or metastatic disease

      • Chemotherapy as part of the first-line therapy given before initiation of NSAI allowed NOTE: *Patients are required to continue to take NSAI until beginning of study treatment.
  • No rapidly progressive visceral disease (i.e., lymphangitis carcinomatosa or diffuse hepatic involvement)
  • Hormone receptor status:

    • Estrogen receptor (ER) and/or progesterone receptor positive tumor
    • No ER-unknown disease

PATIENT CHARACTERISTICS:

Sex

  • Female

Menopausal status

  • Postmenopausal, as defined by 1 of the following criteria:

    • Age 60 and over
    • Age 45 to 59 AND ≥ 12 months since last menstrual period with no prior hysterectomy
    • Any age with prior bilateral oophorectomy

Performance status

  • WHO 0-2

Life expectancy

  • More than 3 months

Hematopoietic

  • Neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3

    • No thrombocytopenia
  • Hemoglobin ≥ 10 g/dL

Hepatic

  • AST and ALT ≤ 2.5 times upper limit of normal (ULN)
  • Alkaline phosphatase ≤ 5 times ULN (unless due to bone metastases)
  • No liver disease

Renal

  • Creatinine < 1.97 mg/dL

Other

  • No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Chemotherapy

  • See Disease Characteristics
  • Prior neoadjuvant or adjuvant chemotherapy allowed

Endocrine therapy

  • See Disease Characteristics
  • Prior tamoxifen as neoadjuvant or adjuvant therapy allowed
  • No systemic corticosteroids that lasted > 15 days within the past 4 weeks

Other

  • More than 4 weeks since prior investigational drugs
  • Concurrent bisphosphonates for bone metastases allowed provided bisphosphonate therapy has been established for ≥ 6 months

    • Concurrent initiation of bisphosphonate allowed provided patient has soft tissue or visceral metastases as the measurable or evaluable target lesion
  • No concurrent anticoagulant therapy
  • No concurrent unlicensed noncancer investigational agents
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00253422

Locations
United Kingdom, England
Institute of Cancer Research - Sutton Recruiting
Sutton, England, United Kingdom, SM2 5NG
Contact: Gill Coombes     44-20-8722-4039        
Royal Marsden - London Recruiting
London, England, United Kingdom, SW3 6JJ
Contact: Stephen R. D. Johnston, MD, PhD, FRCP     44-20-7808-2748        
Sponsors and Collaborators
Institute of Cancer Research, United Kingdom
Investigators
Study Chair: Stephen R. D. Johnston, MD, PhD, FRCP Royal Marsden - London
  More Information

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

Study ID Numbers: CDR0000448616, ICR-CTSU-SOFEA, EU-20531, SSA-04Q200635, ISRCTN44195747, MREC-03677, EUDRACT-2004-000093-30
Study First Received: November 11, 2005
Last Updated: July 23, 2008
ClinicalTrials.gov Identifier: NCT00253422  
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
recurrent breast cancer
stage IV breast cancer
stage IIIB breast cancer
stage IIIC breast cancer

Study placed in the following topic categories:
Anastrozole
Skin Diseases
Fulvestrant
Disease Progression
Breast Neoplasms
Exemestane
Breast Diseases
Recurrence

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

ClinicalTrials.gov processed this record on January 14, 2009