RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using ICI 182780 may fight breast cancer by blocking the activity of estrogen in the tumor cells.

PURPOSE: Phase II trial to study the effectiveness of ICI 182780 in treating patients who have metastatic breast cancer that has not responded to previous hormone therapy.

Condition	Treatment or Intervention	Phase
stage IV breast cancer recurrent breast cancer stage IIIB breast cancer stage IIIC breast cancer	Drug: fulvestrant  Procedure: antiestrogen therapy  Procedure: endocrine therapy  Procedure: hormone therapy	Phase II

Further Study Details: 

OBJECTIVES:

• Determine the complete and partial objective response rate and duration of response in women with metastatic breast cancer who have failed aromatase inhibitor therapy treated with fulvestrant.
• Determine the time to disease progression and overall survival of women treated with this drug.
• Determine the toxicity of this drug in these women.

OUTLINE: Patients receive fulvestrant intramuscularly on day 1. Courses repeat approximately every 28 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 5 years or until disease progression. After disease progression, patients are followed every 3 months for 2 years and then every 6 months for 3 years.

PROJECTED ACCRUAL: Approximately 41-94 patients will be accrued for this study within 10 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed adenocarcinoma of the breast
• Progressive local-regional or metastatic disease
• Unconfirmed new or progressive multiple pulmonary nodules or unequivocal radiographic evidence of multiple bone metastases allowed
• At least 1 measurable lesion
• At least 20 mm by CT scan or MRI OR at least 10 mm by spiral CT scan
• Nonmeasurable disease includes the following:
• Bone lesions
• Leptomeningeal disease
• Ascites
• Pleural/pericardial effusions
• Lymphangitis cutis/pulmonis
• Inflammatory breast disease
• Abdominal masses not confirmed and followed by imaging techniques
• Cystic lesions
• Disease progression after prior third-generation aromatase inhibitor (e.g., anastrozole, exemestane, letrozole, or vorozole)
• Failed no more than 1 prior additive hormonal therapy (e.g., aromatase inhibitor with or without tamoxifen)
• Disease recurrence identified no more than 12 months since the last prior adjuvant tamoxifen treatment
• Oophorectomy, ovarian radiotherapy, and luteinizing hormone-releasing hormone (LH-RH) analogs not considered hormonal therapy regimens
• No brain or leptomeningeal metastases
• No hepatic metastases involving more than one-third of the liver
• No symptomatic pulmonary lymphangitic disease
• Evidence of hormone sensitivity as defined by:
• Relapse after at least 12 months of adjuvant hormonal treatment
• Tumor remission or stabilization before progression for at least 6 months after prior hormonal therapy for advanced disease
• Postmenopausal as defined by one of the following:
• At least 12 months since last menstrual period
• 4-11 months since last menstrual period and follicle-stimulating hormone (FSH) in the postmenopausal range
• Prior castration and castrate FSH levels within the postmenopausal range
• Hysterectomy without oophorectomy (FSH in postmenopausal range if age 60 and under)
• Hormone receptor status:
• Estrogen-receptor and/or progesterone-receptor positive
• At least 10 fmol/mg cytosol protein OR
• Positive by immunohistochemistry

PATIENT CHARACTERISTICS: Age:

• 18 and over

Sex:

• Female

Menopausal status:

• See Disease Characteristics
• Postmenopausal

Performance status:

• ECOG 0-2

Life expectancy:

• At least 3 months

Hematopoietic:

• WBC at least 2,000/mm^3
• Platelet count at least 100,000/mm^3
• No history of bleeding diathesis

Hepatic:

• See Disease Characteristics
• Bilirubin no greater than 0.8 mg/dL above upper limit of normal (ULN)
• INR no greater than 1.6
• No hepatitis B or C
• No severe hepatic impairment

Renal:

• Calcium no greater than 10% above ULN
• Creatinine no greater than 1 mg/dL above ULN
• No severe renal impairment

Cardiovascular:

• No unstable or uncompensated cardiac condition

Pulmonary:

• No unstable or uncompensated respiratory condition

Other:

• HIV negative
• No AIDS
• No other severe condition or systemic disease that would preclude study participation

PRIOR CONCURRENT THERAPY: Biologic therapy:

• Prior trastuzumab (Herceptin) allowed

Chemotherapy:

• Prior adjuvant chemotherapy allowed
• No more than 1 prior chemotherapy regimen for metastatic disease

Endocrine therapy:

• See Disease Characteristics
• More than 4 weeks since prior estrogen replacement therapy
• More than 3 months since prior LH-RH analogs
• No other prior additive hormonal therapy except third-generation aromatase inhibitors or tamoxifen

Radiotherapy:

• See Disease Characteristics
• Concurrent radiotherapy for control of bone pain or other reasons due to established bone lesions allowed if radiotherapy field is no more than 30% of bone marrow

Surgery:

• See Disease Characteristics

Other:

• More than 4 weeks since prior investigational drug for breast cancer
• No concurrent long-term warfarin
• Concurrent bisphosphonates allowed if dose stable
• Concurrent long-term antiplatelet therapy allowed

Alabama
      MBCCOP - Gulf Coast, Mobile,  Alabama,  36607,  United States
Arizona
      CCOP - Mayo Clinic Scottsdale Oncology Program, Scottsdale,  Arizona,  85259-5404,  United States
Florida
      Mayo Clinic, Jacksonville,  Florida,  32224,  United States
Illinois
      Carle Foundation Hospital - Carle Cancer Center, Urbana,  Illinois,  61801,  United States
      CCOP - Illinois Oncology Research Association, Peoria,  Illinois,  61602,  United States
Iowa
      CCOP - Cedar Rapids Oncology Project, Cedar Rapids,  Iowa,  52403-1206,  United States
      CCOP - Iowa Oncology Research Association, Des Moines,  Iowa,  50309-1016,  United States
      Siouxland Hematology-Oncology, Sioux City,  Iowa,  51101-1733,  United States
Kansas
      CCOP - Wichita, Wichita,  Kansas,  67214-3882,  United States
Michigan
      CCOP - Michigan Cancer Research Consortium, Ann Arbor,  Michigan,  48106,  United States
Minnesota
      CCOP - Duluth, Duluth,  Minnesota,  55805,  United States
      CCOP - Metro-Minnesota, Saint Louis Park,  Minnesota,  55416,  United States
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States
Nebraska
      CCOP - Missouri Valley Cancer Consortium, Omaha,  Nebraska,  68106,  United States
North Dakota
      Altru Cancer Center, Grand Forks,  North Dakota,  58201,  United States
      CCOP - Merit Care Hospital, Fargo,  North Dakota,  58122,  United States
      Medcenter One Health System, Bismarck,  North Dakota,  58501-5505,  United States
Ohio
      CCOP - Toledo Community Hospital, Toledo,  Ohio,  43623-3456,  United States
Pennsylvania
      Allegheny General Hospital, Pittsburgh,  Pennsylvania,  15212-4772,  United States
      CCOP - Geisinger Clinic and Medical Center, Danville,  Pennsylvania,  17822-2001,  United States
South Carolina
      CCOP - Upstate Carolina, Spartanburg,  South Carolina,  29303,  United States
South Dakota
      CCOP - Sioux Community Cancer Consortium, Sioux Falls,  South Dakota,  57104,  United States
      Rapid City Regional Hospital, Rapid City,  South Dakota,  57709,  United States
Wisconsin
      CCOP - St. Vincent Hospital Cancer Center, Green Bay, Green Bay,  Wisconsin,  54301,  United States
Canada, Saskatchewan
      Allan Blair Cancer Centre, Regina,  Saskatchewan,  S4T 7T1,  Canada

Study chairs or principal investigators

James N. Ingle, MD,  Study Chair,  Mayo Clinic Cancer Center   

Study ID Numbers:  CDR0000068473; NCCTG-N0032
Record last reviewed:  June 2004
Last Updated:  October 13, 2004
Record first received:  March 3, 2001
ClinicalTrials.gov Identifier:  NCT00012025
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08