Phase I Study of OSI-774 (NSC 718781) for Solid Tumors in Patients With Hepatic or Renal Dysfunction
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 75
- Locations
- 1
- Primary Endpoint
- Maximum tolerated dose (MTD) of OSI-774 determined by dose-limiting toxicities
Study Overview
Brief Summary
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
Detailed Description
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to β (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- β’Histologically confirmed solid tumor, including gliomas and the following epithelial malignancies:
- β’Non-small cell lung
- β’Mesothelioma
- β’Head and neck
- β’Esophageal
- β’Pancreatic
- β’Colorectal carcinoma
- β’Cervical carcinoma
- β’Hepatocellular carcinoma
- β’Metastatic or unresectable disease
- β’Standard curative or palliative therapy does not exist or is no longer effective
- β’Epidermal growth factor receptor (EGFR) positive
- β’Hepatic or renal dysfunction defined as one of the following:
- β’Direct bilirubin 1.0-7.0 mg/dL with any AST
- β’Albumin less than 2.5 g/dL
- β’Creatinine 2.5-5.0 mg/dL
- β’Brain metastases allowed provided patient is asymptomatic, previously treated, has stable disease for at least 2 months, and is not currently receiving steroid therapy
- β’Hormone receptor status:
- β’Not specified
- β’Male or female
- β’Performance status - ECOG 0-2
- β’Granulocyte count at least 1,500/mm^3
- β’Platelet count at least 100,000/mm^3
- β’See Disease Characteristics
- β’No evidence of biliary obstruction
- β’See Disease Characteristics
- β’No evidence of renal obstruction
- β’No symptomatic congestive heart failure
- β’No unstable angina pectoris
- β’No cardiac arrhythmia
- β’No gastrointestinal tract disease that would preclude ability to take oral medications
- β’No requirement for IV alimentation
- β’No active peptic ulcer disease
- β’No prior corneal abnormalities (e.g., dry eye syndrome or Sjogren's syndrome)
- β’No prior congenital abnormality (e.g., Fuch's dystrophy)
- β’No prior abnormal slit-lamp exam using a vital dye (e.g., fluorescein or Bengal-Rose)
- β’No prior abnormal corneal sensitivity test (e.g., Schirmer test or similar tear production test)
- β’No other concurrent uncontrolled illness
- β’No ongoing or active infection
- β’No psychiatric illness or social situation that would preclude study compliance
- β’Not pregnant or nursing
- β’Fertile patients must use effective contraception
- β’No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF)
- β’At least 4 weeks since prior chemotherapy (6 weeks for melphalan or mitomycin)
- β’No prior nitrosoureas
- β’See Disease Characteristics
- β’No concurrent steroids
- β’At least 4 weeks since prior radiotherapy
- β’At least 4 weeks since prior major surgery
- β’No prior surgical procedures affecting absorption
- +8 more not shown
Exclusion Criteria
- Not provided
Arms & Interventions
Treatment (erlotinib hydrochloride)
Patients receive oral erlotinib once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.
Intervention: erlotinib hydrochloride (Drug)
Treatment (erlotinib hydrochloride)
Patients receive oral erlotinib once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.
Intervention: laboratory biomarker analysis (Other)
Outcomes
Primary Outcomes
Maximum tolerated dose (MTD) of OSI-774 determined by dose-limiting toxicities
Time Frame: Within the first 4 weeks treatment
Secondary Outcomes
No secondary outcomes reported