Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Erlotinib in Treating Patients With Solid Tumors and Liver or Kidney Dysfunction

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Completed	18 and over	NCI	CALGB-60101 NCT00030498

Objectives

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

Entry 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

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

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/mm³
• Platelet count at least 100,000/mm³

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

Expected Enrollment

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

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.

Miller AA, Murry DJ, Owzar K, et al.: Phase I and pharmacokinetic study of erlotinib for solid tumors in patients with hepatic or renal dysfunction: CALGB 60101. J Clin Oncol 25 (21): 3055-60, 2007.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Cancer and Leukemia Group B

Antonius Miller, MD, Protocol chair		Ph: 336-713-4392; 800-446-2255

Registry Information
Official Title		Phase I Study of OSI-774 (NSC 718781) for Solid Tumors in Patients with Hepatic or Renal Dysfunction
Trial Start Date		2001-12-15
Trial Completion Date		2007-07-20
Registered in ClinicalTrials.gov		NCT00030498
Date Submitted to PDQ		2001-12-04
Information Last Verified		2008-12-17
NCI Grant/Contract Number		CA31946

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