RATIONALE: Some tumors need growth factors produced by the body's white blood cells to keep growing. Erlotinib may interfere with the growth factor and may stop the tumor from growing. PURPOSE: Phase II trial to study the effectiveness of erlotinib in treating women who have progressive or recurrent, locally advanced or metastatic breast cancer.

Condition	Treatment or Intervention	Phase
stage IIIB breast cancer stage IIIA breast cancer stage IV breast cancer recurrent breast cancer	Procedure: protein tyrosine kinase inhibitor therapy  Procedure: enzyme inhibitor therapy  Drug: erlotinib	Phase II

Further Study Details: 

OBJECTIVES: I. Determine the objective response rate in women with progressive or recurrent, locally advanced or metastatic breast cancer treated with erlotinib. II. Determine the safety of this drug in these patients. III. Determine the duration of objective response, time to disease progression, and duration of survival in patients treated with this drug. IV. Determine the proportion of patients with stable disease for at least 4 months after treatment with this drug. V. Determine potential factors that contribute to inter-patient variability in pharmacokinetic behavior in patients treated with this drug. VI. Determine exposure-effect relationships in patients treated with this drug.

PROTOCOL OUTLINE: This is a multicenter study. Patients are stratified according to disease progression on or after prior therapy (anthracycline, taxane, and capecitabine vs at least 1 chemotherapy regimen for metastatic disease). Patients receive oral erlotinib once daily. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed every 2 months.

PROJECTED ACCRUAL: A total of 42-200 patients (21-150 in stratum 1 and 21-50 in stratum 2) will be accrued for this study.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed incurable locally advanced or metastatic breast cancer
• Measurable disease; At least 2 cm in diameter; At least 1 cm by spiral CT scan; Disease at previously irradiated sites considered measurable if there is clear disease progression after radiotherapy
• Disease progression during or after prior therapy with at least 1 chemotherapy regimen for metastatic disease (stratum 2) OR with an anthracycline, taxane, and capecitabine (stratum 1); Therapy in combination or in sequence for locally advanced or metastatic disease and/or as adjuvant therapy allowed; Disease recurrence in stratum 1 must have occurred during or within 12 months after completion of adjuvant therapy
• HER2 negative, unknown, or positive with disease progression after prior trastuzumab (Herceptin) therapy
• No pleural effusions or blastic bone lesions as only manifestations of metastatic disease
• No symptomatic or untreated brain metastases; Brain metastases allowed if neurologically stable and at least 4 weeks since prior corticosteroid therapy
• Hormone receptor status: Not specified

--Prior/Concurrent Therapy--

• Biologic therapy: See Disease Characteristics; At least 21 days since prior immunotherapy; No prior therapy with an agent designed to target epidermal growth factor receptor (EGFR) or EGFR-specific tyrosine kinase activity
• Chemotherapy: See Disease Characteristics; At least 21 days since prior chemotherapy (6 weeks for nitrosoureas or mitomycin); No prior cumulative dose of doxorubicin greater than 450 mg/m2; No concurrent chemotherapy for breast cancer
• Endocrine therapy: See Disease Characteristics; At least 21 days since prior hormonal therapy; No concurrent hormonal therapy for breast cancer
• Radiotherapy: See Disease Characteristics; At least 21 days since prior radiotherapy; No concurrent radiotherapy for breast cancer
• Surgery: At least 21 days since prior major surgery or biopsy of parenchymal organ; No prior surgical procedure that would affect absorption; No concurrent significant surgical procedure
• Other: No other concurrent experimental anticancer medications; No other concurrent antitumor therapy

--Patient Characteristics--

• Sex: Female
• Menopausal status: Not specified
• Performance status: ECOG 0-2
• Life expectancy: At least 3 months
• Hematopoietic: Granulocyte count greater than 1,500/mm3; Platelet count at least 100,000/mm3; Hemoglobin at least 9 g/dL (transfusion allowed)
• Hepatic: Bilirubin less than 1.5 times upper limit of normal (ULN); ALT and AST less than 2.5 times ULN (no greater than 5 times ULN if liver metastases present); Alkaline phosphatase less than 2.5 times ULN (no greater than 4 times ULN if liver or bone metastases present); Albumin greater than 3.0 g/dL
• Renal: Creatinine less than 1.5 times ULN OR Creatinine clearance greater than 60 mL/min; Calcium no greater than 11.5 mg/dL
• Cardiovascular: Ejection fraction at least lower limit of normal by MUGA scan or echocardiogram; No uncontrolled hypertension No unstable angina; No congestive heart failure; No myocardial infarction within the past 6 months; No cardiac arrhythmia requiring medication
• Other: Not pregnant or nursing; Negative pregnancy test; Fertile patients must use effective contraception; No other unstable systemic disease; No active infection; No significant traumatic injury within the past 21 days; No history of abnormalities of the cornea (e.g., dry eye syndrome or Sjogren's syndrome), congenital abnormality (e.g., Fuch's dystrophy), abnormal slit-lamp examination using vital dye (e.g., fluorescein or Bengal-Rose), and/or abnormal corneal sensitivity test (e.g., Schirmer test or similar tear production test); No gastrointestinal disease resulting in an inability to take oral medication or requiring IV alimentation; No active peptic ulcer disease; No other prior malignancy within the past 5 years except adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer; No history of other diseases, metabolic dysfunction, or physical or laboratory finding indicative of a disease or condition that would preclude study

California
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-1781,  United States
Idaho
      Mountain States Tumor Institute, Boise,  Idaho,  83712,  United States
Illinois
      Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago,  Illinois,  60611-3013,  United States
      Rush Cancer Institute, Chicago,  Illinois,  60612,  United States
Indiana
      Indiana Cancer Pavilion, Indianapolis,  Indiana,  46202,  United States
New Mexico
      New Mexico Cancer Care, Santa Fe,  New Mexico,  87505-7670,  United States
New York
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States
Texas
      Texas Cancer Care, Fort Worth,  Texas,  76104,  United States
Washington
      Seattle Cancer Care Alliance, Seattle,  Washington,  98109,  United States

Study chairs or principal investigators

Robert Justice,  Study Chair,  Genentech   

Study ID Numbers:  CDR0000068902; GENENTECH-OSI2288g; NCI-G01-2012; DFCI-01059; DFCI-2001-P-000327/1; MSKCC-01068
Record last reviewed:  February 2004
Last Updated:  October 13, 2004
Record first received:  September 13, 2001
ClinicalTrials.gov Identifier:  NCT00024219
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08