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

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00030498

Collaborator

(none)

Enrollment

Location

Arm

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Adult Anaplastic Astrocytoma Adult Anaplastic Ependymoma Adult Anaplastic Oligodendroglioma Adult Brain Stem Glioma Adult Diffuse Astrocytoma Adult Ependymoblastoma Adult Giant Cell Glioblastoma Adult Glioblastoma Adult Gliosarcoma Adult Mixed Glioma Adult Myxopapillary Ependymoma Adult Oligodendroglioma Adult Pilocytic Astrocytoma Adult Primary Hepatocellular Carcinoma Adult Subependymoma Advanced Adult Primary Liver Cancer Advanced Malignant Mesothelioma Male Breast Cancer Recurrent Adenoid Cystic Carcinoma of the Oral Cavity Recurrent Adult Brain Tumor Recurrent Adult Primary Liver Cancer Recurrent Anal Cancer Recurrent Basal Cell Carcinoma of the Lip Recurrent Bladder Cancer Recurrent Breast Cancer Recurrent Cervical Cancer Recurrent Colon Cancer Recurrent Esophageal Cancer Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity Recurrent Lymphoepithelioma of the Nasopharynx Recurrent Lymphoepithelioma of the Oropharynx Recurrent Malignant Mesothelioma Recurrent Metastatic Squamous Neck Cancer With Occult Primary Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity Recurrent Mucoepidermoid Carcinoma of the Oral Cavity Recurrent Non-small Cell Lung Cancer Recurrent Ovarian Epithelial Cancer Recurrent Pancreatic Cancer Recurrent Prostate Cancer Recurrent Rectal Cancer Recurrent Salivary Gland Cancer Recurrent Squamous Cell Carcinoma of the Hypopharynx Recurrent Squamous Cell Carcinoma of the Larynx Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity Recurrent Squamous Cell Carcinoma of the Nasopharynx Recurrent Squamous Cell Carcinoma of the Oropharynx Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity Recurrent Verrucous Carcinoma of the Larynx Recurrent Verrucous Carcinoma of the Oral Cavity Stage II Esophageal Cancer Stage II Pancreatic Cancer Stage III Esophageal Cancer Stage III Pancreatic Cancer Stage IIIB Non-small Cell Lung Cancer Stage IV Adenoid Cystic Carcinoma of the Oral Cavity Stage IV Anal Cancer Stage IV Basal Cell Carcinoma of the Lip Stage IV Bladder Cancer Stage IV Breast Cancer Stage IV Colon Cancer Stage IV Esophageal Cancer Stage IV Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity Stage IV Inverted Papilloma of the Paranasal Sinus and Nasal Cavity Stage IV Lymphoepithelioma of the Nasopharynx Stage IV Lymphoepithelioma of the Oropharynx Stage IV Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity Stage IV Mucoepidermoid Carcinoma of the Oral Cavity Stage IV Non-small Cell Lung Cancer Stage IV Ovarian Epithelial Cancer Stage IV Pancreatic Cancer Stage IV Prostate Cancer Stage IV Rectal Cancer Stage IV Salivary Gland Cancer Stage IV Squamous Cell Carcinoma of the Hypopharynx Stage IV Squamous Cell Carcinoma of the Larynx Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity Stage IV Squamous Cell Carcinoma of the Nasopharynx Stage IV Squamous Cell Carcinoma of the Oropharynx Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity Stage IV Verrucous Carcinoma of the Larynx Stage IV Verrucous Carcinoma of the Oral Cavity Stage IVA Cervical Cancer Stage IVB Cervical Cancer Unspecified Adult Solid Tumor, Protocol Specific Untreated Metastatic Squamous Neck Cancer With Occult Primary	Drug: erlotinib hydrochloride Other: laboratory biomarker analysis	Phase 1

Detailed Description

PRIMARY 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

75 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase I Study of OSI-774 (NSC 718781) for Solid Tumors in Patients With Hepatic or Renal Dysfunction

Study Start Date :

Dec 1, 2001

Actual Primary Completion Date :

Jul 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (erlotinib hydrochloride) Patients receive oral erlotinib once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.	Drug: erlotinib hydrochloride Given orally Other Names: CP-358,774 erlotinib OSI-774 Other: laboratory biomarker analysis Correlative studies

Arm

Intervention/Treatment

Experimental: Treatment (erlotinib hydrochloride)

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

Drug: erlotinib hydrochloride

Given orally

Other Names:

CP-358,774

erlotinib

OSI-774

Other: laboratory biomarker analysis

Correlative studies

Outcome Measures

Primary Outcome Measures

Maximum tolerated dose (MTD) of OSI-774 determined by dose-limiting toxicities [Within the first 4 weeks treatment]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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
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