Clinical trial NCT00030498: Erlotinib in Treating Patients With Solid Tumors and Liver or Kidney Dysfunction
Official title: Phase I Study of OSI-774 (NSC 718781) for Solid Tumors in Patients With Hepatic or Renal Dysfunction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: 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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Maximum tolerated dose (MTD) of OSI-774 determined by dose-limiting toxicities
timeFrame: Within the first 4 weeks treatment
Secondary outcomes:
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Cancer and Leukemia Group B
state: Illinois
Study officials:
affiliation: Cancer and Leukemia Group B
name: Antonius Miller
role: PRINCIPAL_INVESTIGATOR
References: