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

Phase 1

Completed

• 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
• Interventions: Drug: erlotinib hydrochloride; Other: laboratory biomarker analysis

• Registration Number: NCT00030498
• Lead Sponsor: National Cancer Institute (NCI)

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.

Study Timeline

• Study Start: 2001-12
• Study First Submitted: 2002-02-14
• Study First Submitted QC: 2003-01-26
• Study First Posted: 2003-01-27
• Primary Completion: 2007-07
• Status Verified: 2013-01
• Last Update Submitted: 2013-01-15
• Last Update Posted: 2013-01-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 75

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (erlotinib hydrochloride)	erlotinib hydrochloride	Patients receive oral erlotinib once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.
Treatment (erlotinib hydrochloride)	laboratory biomarker analysis	Patients receive oral erlotinib once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

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

Trial Locations

Locations (1)

Cancer and Leukemia Group B; 🇺🇸 Chicago, Illinois, United States