Phase I Study of OSI-774 (NSC 718781) for Solid Tumors in Patients With Hepatic or Renal Dysfunction
Phase I Study of OSI-774 (NSC 718781) for Solid Tumors in Patients With Hepatic or Renal Dysfunction
Phase I trial to study the effectiveness of erlotinib in treating patients who have metastatic or unresectable solid tumors and liver or kidney dysfunction. Biological therapies such as erlotinib may interfere with the growth of tumor cells and slow the growth of the tumor
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose of erlotinib in patients with solid tumors and hepatic or renal dysfunction.
II. 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.
Inclusion Criteria:
Histologically confirmed solid tumor, including gliomas and the following epithelial malignancies:
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:
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:
Male or female
Performance status - ECOG 0-2
Granulocyte count at least 1,500/mm^3
Platelet count at least 100,000/mm^3
See Disease Characteristics
No evidence of biliary obstruction
See Disease Characteristics
No evidence of renal obstruction
No symptomatic congestive heart failure
No unstable angina pectoris
No cardiac arrhythmia
No gastrointestinal tract disease that would preclude ability to take oral medications
No requirement for IV alimentation
No active peptic ulcer disease
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)
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
No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF)
At least 4 weeks since prior chemotherapy (6 weeks for melphalan or mitomycin)
No prior nitrosoureas
See Disease Characteristics
No concurrent steroids
At least 4 weeks since prior radiotherapy
At least 4 weeks since prior major surgery
No prior surgical procedures affecting absorption
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