RATIONALE: Biological therapies such as erlotinib may interfere with the growth of tumor cells and slow the growth of the tumor.

PURPOSE: Phase I trial to study the effectiveness of erlotinib in treating patients who have metastatic or unresectable solid tumors and liver or kidney dysfunction.

Condition	Treatment or Intervention	Phase
Cancer	Drug: erlotinib  Procedure: enzyme inhibitor therapy  Procedure: protein tyrosine kinase inhibitor therapy	Phase I

Further Study Details: 

OBJECTIVES:

• Determine the maximum tolerated dose of erlotinib in patients with solid tumors and hepatic or renal dysfunction.
• Determine the pharmacokinetics of this drug in these patients.

OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to hepatic or renal dysfunction (albumin less than 2.5 g/dL, direct bilirubin less than 1.0 mg/dL, any AST, and creatinine normal vs direct bilirubin 1.0-7.0 mg/dL, any AST, and creatinine normal vs creatinine 2.5-5.0 mg/dL, albumin 2.5 g/dL or greater, AST less than 3 times upper limit of normal, and direct bilirubin less than 1.0 mg/dL).

Patients receive oral erlotinib once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, at least 6 evaluable patients are treated at that dose.

PROJECTED ACCRUAL: A maximum of 75 patients will be accrued for this study.

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

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed solid tumor, including gliomas and the following epithelial malignancies:
• Non-small cell lung
• Mesothelioma
• Breast
• Head and neck
• Esophageal
• Pancreatic
• Bladder
• Prostate
• Ovarian
• Anal
• Colorectal carcinoma
• Cervical carcinoma
• Hepatocellular carcinoma
• Metastatic or unresectable disease
• Standard curative or palliative therapy does not exist or is no longer effective
• Epidermal growth factor receptor (EGFR) positive
• Hepatic or renal dysfunction defined as one of the following:
• Direct bilirubin 1.0-7.0 mg/dL with any AST
• Albumin less than 2.5 g/dL
• Creatinine 2.5-5.0 mg/dL
• Brain metastases allowed provided patient is asymptomatic, previously treated, has stable disease for at least 2 months, and is not currently receiving steroid therapy
• 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:

• Not specified

Hematopoietic:

• Granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• See Disease Characteristics
• No evidence of biliary obstruction

Renal:

• See Disease Characteristics
• No evidence of renal obstruction

Cardiovascular:

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Gastrointestinal:

• No gastrointestinal tract disease that would preclude ability to take oral medications
• No requirement for IV alimentation
• No active peptic ulcer disease

Ophthalmic:

• No prior corneal abnormalities (e.g., dry eye syndrome or Sjogren's syndrome)
• No prior congenital abnormality (e.g., Fuch's dystrophy)
• No prior abnormal slit-lamp exam using a vital dye (e.g., fluorescein or Bengal-Rose)
• No prior abnormal corneal sensitivity test (e.g., Schirmer test or similar tear production test)

Other:

• No other concurrent uncontrolled illness
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy:

• No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF)

Chemotherapy:

• At least 4 weeks since prior chemotherapy (6 weeks for melphalan or mitomycin)
• No prior nitrosoureas

Endocrine therapy:

• See Disease Characteristics
• No concurrent steroids

Radiotherapy:

• At least 4 weeks since prior radiotherapy

Surgery:

• At least 4 weeks since prior major surgery
• No prior surgical procedures affecting absorption

Other:

• No prior EGFR-targeting therapies, including gefitinib or Imclone C-225
• At least 3 months since prior suramin
• More than 7 days since prior grapefruit juice
• More than 7 days since other prior CYP3A4 inhibitors
• No concurrent grapefruit juice
• No concurrent CYP3A4 inducers, substrates, or other inhibitors
• No concurrent medications known to affect hepatic or renal function, including antiseizure medication or nonsteroidal anti-inflammatory agents
• No concurrent combination anti-retroviral therapy for HIV-positive patients

Alabama
      Northeast Alabama Regional Medical Center, Anniston,  Alabama,  36207,  United States; Recruiting
California
      Naval Medical Center - San Diego, San Diego,  California,  92134-3202,  United States; Recruiting
      UCSF Comprehensive Cancer Center, San Francisco,  California,  94115,  United States; Recruiting
      Veterans Affairs Medical Center - San Diego, San Diego,  California,  92161,  United States; Recruiting
District of Columbia
      Lombardi Cancer Center at Georgetown University Medical Center, Washington,  District of Columbia,  20007,  United States; Recruiting
      Veterans Affairs Medical Center - Washington, DC, Washington,  District of Columbia,  20422,  United States; Recruiting
Florida
      Memorial Cancer Institute at Memorial Regional Hospital, Hollywood,  Florida,  33021,  United States; Recruiting
Illinois
      CCOP - Illinois Oncology Research Association, Peoria,  Illinois,  61615-7828,  United States; Recruiting
      Louis A. Weiss Memorial Hospital, Chicago,  Illinois,  60640,  United States; Recruiting
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637-1470,  United States; Recruiting
      West Suburban Center for Cancer Care, River Forest,  Illinois,  60305,  United States; Recruiting
Indiana
      Fort Wayne Medical Oncology and Hematology, Incorporated, Fort Wayne,  Indiana,  46885-5099,  United States; Recruiting
Iowa
      Holden Comprehensive Cancer Center at University of Iowa, Iowa City,  Iowa,  52242-1009,  United States; Recruiting
Kentucky
      Baptist Hospital East - Louisville, Louisville,  Kentucky,  40207,  United States; Recruiting
Maryland
      Greenebaum Cancer Center at University of Maryland Medical Center, Baltimore,  Maryland,  21201,  United States; Recruiting
Michigan
      Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph, Saint Joseph,  Michigan,  49085,  United States; Recruiting
Nevada
      Veterans Affairs Medical Center - Las Vegas, Las Vegas,  Nevada,  89106,  United States; Recruiting
New Hampshire
      New Hampshire Oncology-Hematology, PA - Hooksett, Hooksett,  New Hampshire,  03106,  United States; Recruiting
      Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center, Lebanon,  New Hampshire,  03756-0002,  United States; Recruiting
New Jersey
      Cancer Institute of New Jersey at the Cooper University Hospital, Camden,  New Jersey,  08103,  United States; Recruiting
New York
      Elmhurst Hospital Center, Elmhurst,  New York,  11373,  United States; Recruiting
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States; Recruiting
      North Shore University Hospital, Manhasset,  New York,  11030,  United States; Recruiting
      Queens Cancer Center of Queens Hospital, Jamaica,  New York,  11432,  United States; Recruiting
      Roswell Park Cancer Institute, Buffalo,  New York,  14263-0001,  United States; Recruiting
North Carolina
      Cape Fear Valley Medical Center, Fayetteville,  North Carolina,  28302-2000,  United States; Recruiting
      Comprehensive Cancer Center at Moore Regional Hospital, Pinehurst,  North Carolina,  28374,  United States; Recruiting
      Comprehensive Cancer Center at Wake Forest University, Winston Salem,  North Carolina,  27157-1082,  United States; Recruiting
      Lenoir Memorial Cancer Center, Kinston,  North Carolina,  28503-1678,  United States; Recruiting
      NorthEast Oncology Associates - Concord, Concord,  North Carolina,  28025,  United States; Recruiting
      Veterans Affairs Medical Center - Asheville, Asheville,  North Carolina,  28805-9913,  United States; Recruiting
      Zimmer Cancer Center at New Hanover Regional Medical Center, Wilmington,  North Carolina,  28402-9025,  United States; Recruiting
Ohio
      Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University, Columbus,  Ohio,  43210-1240,  United States; Recruiting
Oklahoma
      Oklahoma University Medical Center, Oklahoma City,  Oklahoma,  73104,  United States; Recruiting
Virginia
      Martha Jefferson Hospital, Charlottesville,  Virginia,  22902,  United States; Recruiting
      Oncology and Hematology Associates of Southwest Virginia, Incorporated - Roanoke, Roanoke,  Virginia,  24014,  United States; Recruiting
      Virginia Oncology Associates - Norfolk, Norfolk,  Virginia,  23502,  United States; Recruiting
West Virginia
      St. Mary's Medical Center, Huntington,  West Virginia,  25701,  United States; Recruiting
Wisconsin
      Ministry Medical Group at Saint Mary's Hospital, Rhinelander,  Wisconsin,  54501,  United States; Recruiting

Study chairs or principal investigators

Antonius A. Miller, MD,  Study Chair,  Comprehensive Cancer Center of Wake Forest University   

Study ID Numbers:  CDR0000069170; CALGB-60101; NCT00030498
Record last reviewed:  October 2004
Last Updated:  April 4, 2005
Record first received:  February 14, 2002
ClinicalTrials.gov Identifier:  NCT00030498
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08