ICI 182780 in Treating Women With Metastatic Breast Cancer

Alliance for Clinical Trials in Oncology

Status and phase: Completed; Phase 2

Conditions: Breast Cancer

Treatments: Drug: fulvestrant

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00012025

CDR0000068473 (Registry Identifier)

NCCTG-N0032

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 80 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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80 participants in 1 patient group

fulvestrant

Experimental group

Description:

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.

Treatment:

Drug: fulvestrant