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

National Cancer Institute (NCI)

Status and phase

Completed

Phase 1

Conditions

Adult Anaplastic Ependymoma

Recurrent Squamous Cell Carcinoma of the Hypopharynx

Stage II Esophageal Cancer

Stage IV Non-small Cell Lung Cancer

Stage IV Lymphoepithelioma of the Oropharynx

Recurrent Malignant Mesothelioma

Recurrent Anal Cancer

Adult Glioblastoma

Stage IV Inverted Papilloma of the Paranasal Sinus and Nasal Cavity

Recurrent Cervical Cancer

Stage IV Squamous Cell Carcinoma of the Oropharynx

Advanced Adult Primary Liver Cancer

Adult Subependymoma

Adult Oligodendroglioma

Recurrent Mucoepidermoid Carcinoma of the Oral Cavity

Recurrent Verrucous Carcinoma of the Larynx

Recurrent Squamous Cell Carcinoma of the Oropharynx

Recurrent Pancreatic Cancer

Stage IV Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity

Adult Gliosarcoma

Stage IV Squamous Cell Carcinoma of the Hypopharynx

Stage III Pancreatic Cancer

Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity

Stage III Esophageal Cancer

Advanced Malignant Mesothelioma

Adult Ependymoblastoma

Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity

Recurrent Ovarian Epithelial Cancer

Stage IVB Cervical Cancer

Adult Giant Cell Glioblastoma

Recurrent Non-small Cell Lung Cancer

Adult Primary Hepatocellular Carcinoma

Untreated Metastatic Squamous Neck Cancer With Occult Primary

Stage IV Rectal Cancer

Stage IV Esophageal Cancer

Stage IV Anal Cancer

Adult Anaplastic Oligodendroglioma

Stage IV Mucoepidermoid Carcinoma of the Oral Cavity

Stage IV Colon Cancer

Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity

Recurrent Bladder Cancer

Adult Myxopapillary Ependymoma

Stage IV Bladder Cancer

Stage II Pancreatic Cancer

Recurrent Rectal Cancer

Recurrent Lymphoepithelioma of the Nasopharynx

Recurrent Breast Cancer

Recurrent Salivary Gland Cancer

Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity

Stage IV Salivary Gland Cancer

Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity

Adult Brain Stem Glioma

Adult Diffuse Astrocytoma

Recurrent Esophageal Cancer

Adult Anaplastic Astrocytoma

Stage IV Ovarian Epithelial Cancer

Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity

Recurrent Adenoid Cystic Carcinoma of the Oral Cavity

Male Breast Cancer

Recurrent Basal Cell Carcinoma of the Lip

Stage IV Adenoid Cystic Carcinoma of the Oral Cavity

Stage IV Basal Cell Carcinoma of the Lip

Recurrent Adult Brain Tumor

Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity

Stage IV Squamous Cell Carcinoma of the Larynx

Recurrent Verrucous Carcinoma of the Oral Cavity

Stage IV Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity

Stage IV Lymphoepithelioma of the Nasopharynx

Recurrent Lymphoepithelioma of the Oropharynx

Stage IVA Cervical Cancer

Adult Pilocytic Astrocytoma

Stage IV Verrucous Carcinoma of the Larynx

Recurrent Adult Primary Liver Cancer

Unspecified Adult Solid Tumor, Protocol Specific

Stage IV Verrucous Carcinoma of the Oral Cavity

Recurrent Colon Cancer

Stage IV Pancreatic Cancer

Adult Mixed Glioma

Recurrent Squamous Cell Carcinoma of the Larynx

Recurrent Squamous Cell Carcinoma of the Nasopharynx

Recurrent Metastatic Squamous Neck Cancer With Occult Primary

Stage IIIB Non-small Cell Lung Cancer

Stage IV Squamous Cell Carcinoma of the Nasopharynx

Stage IV Prostate Cancer

Recurrent Prostate Cancer

Stage IV Breast Cancer

Treatments

Other: laboratory biomarker analysis

Drug: erlotinib hydrochloride

Study type

Interventional

Funder types

NIH

Identifiers

NCT00030498

CDR0000069170 (Registry Identifier)

U10CA031946 (U.S. NIH Grant/Contract)

NCI-2012-01868

CALGB-60101

Details and patient eligibility

About

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

Full 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.

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.

Enrollment

75 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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