RATIONALE: Drugs used in chemotherapy such as gemcitabine use 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.

Condition	Treatment or Intervention	Phase
Male Breast Cancer recurrent breast cancer stage IV breast cancer	Drug: erlotinib  Drug: gemcitabine  Procedure: chemotherapy  Procedure: enzyme inhibitor therapy  Procedure: protein tyrosine kinase inhibitor therapy	Phase II

Further Study Details: 

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 are followed every 6 weeks for up to 5 years or until disease progression (PD); patients with PD are then followed every 3 months for up to 5 years.

PROJECTED ACCRUAL: A total of 5-56 patients will be accrued for this study within 20 months.

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

Criteria

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

Arizona
      CCOP - Mayo Clinic Scottsdale Oncology Program, Scottsdale,  Arizona,  85259-5404,  United States
Florida
      Mayo Clinic - Jacksonville, Jacksonville,  Florida,  32224,  United States
Illinois
      CCOP - 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
Louisiana
      CCOP - Ochsner, New Orleans,  Louisiana,  70121,  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
      CentraCare Health Plaza, Saint Cloud,  Minnesota,  56303,  United States
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States
Nebraska
      CCOP - Missouri Valley Cancer Consortium, Omaha,  Nebraska,  68106,  United States
North Dakota
      CCOP - Merit Care Hospital, Fargo,  North Dakota,  58122,  United States
      Medcenter One Health System, Bismarck,  North Dakota,  58501-5505,  United States
Ohio
      CCOP - Dayton, Dayton,  Ohio,  45429,  United States
      CCOP - Toledo Community Hospital, Toledo,  Ohio,  43623-3456,  United States
Oklahoma
      CCOP - Oklahoma, Tulsa,  Oklahoma,  74136,  United States
Pennsylvania
      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

Study chairs or principal investigators

Edith A. Perez, MD,  Study Chair,  Mayo Clinic - Jacksonville   
Stephan Thome, MD,  Oncology Hematology West, P.C. - Omaha Bergan   

Study ID Numbers:  CDR0000298778; NCCTG-N0234
Record last reviewed:  August 2004
Last Updated:  October 13, 2004
Record first received:  May 6, 2003
ClinicalTrials.gov Identifier:  NCT00059852
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08