Erlotinib and Gemcitabine in Treating Patients With Metastatic Breast Cancer Previously Treated With An Anthracycline and/or a Taxane

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy such as gemcitabine work in different ways to stop tumor cells from dividing so they stop growing or die. Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Combining gemcitabine with erlotinib may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining gemcitabine with erlotinib in treating patients who have metastatic breast cancer that has been previously treated with an anthracycline and/or a taxane.

Detailed Description
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OBJECTIVES: Determine the anti-tumor activity of erlotinib and gemcitabine in patients with metastatic breast cancer previously treated with anthracycline and/or taxane. Determine the adverse event profile of this regimen in these patients. Determine whether epidermal growth factor receptor and HER-2 receptor intensity and serum concentrations have an impact on clinical response in patients treated with this regimen. Determine the impact of genetic differences in proteins involved in drug response (transport, metabolism, and mechanism of action) on clinical response and adverse events associated with gemcitabine in these patients. OUTLINE: This is a multicenter study. Patients receive gemcitabine IV on days 1 and 8 and oral erlotinib on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response are followed every 6 weeks for up to 5 years or until disease progression (PD). Patients discontinuing study therapy for any other reason are followed every 3 months until PD and then every 6 months for up to 5 years.

Official Title
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A Phase II Study of OSI-774 (Tarceva) and Gemcitabine for Patients With Metastatic Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: erlotinib hydrochloride
* Drug: gemcitabine hydrochloride


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed breast cancer Clinical evidence of metastatic disease Candidate for first- or second-line chemotherapy for metastatic disease Must have received prior anthracycline or taxane therapy (may have had both in the neoadjuvant, adjuvant, or metastatic setting) At least 1 measurable lesion at least 20 mm by CT scan or MRI OR at least 10 mm by spiral CT scan The following are not considered measurable disease: Small lesions less than 20 mm by CT scan or MRI Bone lesions Ascites Pleural/pericardial effusion Inflammatory breast disease Lymphangitis cutis/pulmonis Abdominal masses not confirmed and followed by imaging techniques Cystic lesions No active CNS metastases (treated CNS metastases stable for more than 8 weeks are allowed) Hormone receptor status: Not specified PATIENT CHARACTERISTICS: Age 18 and over Sex Male or female Menopausal status Not specified Performance status ECOG 0-2 Life expectancy At least 3 months Hematopoietic Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 8.5 g/dL Hepatic Bilirubin no greater than 1.5 times upper limit of normal (ULN) AST no greater than 3 times ULN Alkaline phosphatase no greater than 3 times ULN Renal Creatinine no greater than 1.5 times ULN Cardiovascular No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia Gastrointestinal No inability to take oral or nasogastric medication No requirement for IV alimentation No active peptic ulcer disease Ophthalmic No abnormalities of the cornea based on history (e.g., dry eye syndrome or Sjögren's syndrome) No congenital abnormality (e.g., Fuch's dystrophy) No abnormal slit-lamp examination using a vital dye (e.g., fluorescein or Bengal-Rose) No abnormal corneal sensitivity test (Schirmer test or similar tear production test) Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Sub-dermal implants and condoms are not considered acceptable forms of contraception No other invasive non-breast malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer No ongoing or active infection No psychiatric illness or social situation that would preclude study compliance No other concurrent uncontrolled illness PRIOR CONCURRENT THERAPY: Biologic therapy At least 2 weeks since prior immunotherapy No prior cetuximab Chemotherapy At least 2 weeks since prior chemotherapy and recovered No more than 1 prior chemotherapy regimen for metastatic disease No more than 2 prior chemotherapy regimens total, including adjuvant therapy Endocrine therapy Prior hormonal therapy allowed in metastatic and/or adjuvant setting Radiotherapy At least 2 weeks since prior radiotherapy No prior radiotherapy to more than 25% of bone marrow No prior strontium chloride Sr 89 Surgery More than 4 weeks since prior major surgery No prior surgical procedures affecting absorption Other No prior epidermal growth factor receptor-targeting therapies (e.g., gefitinib or EKB-569) No concurrent combination antiretroviral therapy for HIV-positive patients No other concurrent antitumor therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: gemcitabine + erlotinib<br>Patients receive gemcitabine IV on days 1 and 8 and oral erlotinib on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response are followed every 6 weeks for up to 5 years or until disease progression (PD). Patients discontinuing study therapy for any other reason are followed every 3 months until PD and then every 6 months for up to 5 years. | Drug: erlotinib hydrochloride<br> <br> Drug: gemcitabine hydrochloride<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| response rate |  | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival |  | Up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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male breast cancer, recurrent breast cancer, stage IV breast cancer