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Erlotinib in Treating Patients With Unresectable Liver Cancer and Liver Dysfunction
This study has been completed.
Sponsors and Collaborators: M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00047346
  Purpose

RATIONALE: Biological therapies such as erlotinib may interfere with the growth of tumor cells and slow the growth of the tumor.

PURPOSE: Phase I trial to study the effectiveness of erlotinib in treating patients who have unresectable liver cancer and liver dysfunction.


Condition Intervention Phase
Liver Cancer
Drug: erlotinib hydrochloride
Phase I

MedlinePlus related topics: Cancer Liver Cancer
Drug Information available for: Erlotinib Erlotinib hydrochloride Epidermal Growth Factor Tyrosine
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment
Official Title: A Dose-Finding, Safety, And Pharmacokinetic Study Of The Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor OSI-774 (NSC 718781) In Patients With Unresectable Hepatocellular Carcinoma And Moderate Hepatic Dysfunction

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Dose-limiting toxicity and maximum tolerated dose as measured by NCI CTCAE v3.0 continuously [ Designated as safety issue: Yes ]
  • Pharmacokinetic and pharmacodynamic profile as measured by compartmental and noncompartmental models during first course of treatment [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Antitumor effect as measured by NCI RECIST criteria every 8 weeks [ Designated as safety issue: No ]

Study Start Date: August 2002
Detailed Description:

OBJECTIVES:

Primary

  • Determine the maximum tolerated dose of erlotinib in patients with unresectable hepatocellular carcinoma and moderate hepatic dysfunction.
  • Determine the dose-limiting toxicity of this drug in these patients.
  • Determine the pharmacokinetic and pharmacodynamic profiles of this drug in these patients.

Secondary

  • Determine any possible antitumor effects of this drug, in terms of partial and complete response, in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive oral erlotinib once daily. Courses repeat every 28 days 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.

PROJECTED ACCRUAL: Approximately 12-24 patients will be accrued for this study within 4-24 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed unresectable hepatocellular carcinoma (HCC) with or without extrahepatic metastasis

    • No fibrolamellar HCC
  • No more than 2 prior therapies for HCC, including systemic chemotherapy, chemoembolization, hepatic arterial infusion of chemotherapeutic agents, and other novel agents
  • Measurable disease

    • At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR at least 10 mm by spiral CT scan
  • Moderate hepatic dysfunction with any of the following:

    • Bilirubin 2-4 g/dL
    • Albumin < 2.5 g/dL
    • Ascites
    • PT 2-4 seconds > upper limit of normal (ULN)
    • AST/ALT 2.6-10 times > ULN
  • No known brain metastases
  • No ascites that are refractory to conservative management (e.g., sodium restriction to 50 mEq/day dietary sodium and fluid restrictions and/or diuretics)

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • ECOG 0-2

Life expectancy

  • At least 16 weeks

Hematopoietic

  • Granulocyte count ≥ 1,500/mm^3
  • Platelet count ≥ 60,000/mm^3
  • Hemoglobin ≥ 10 g/dL

Hepatic

  • See Disease Characteristics
  • No decompensated liver disease
  • No jaundice
  • No portosystemic encephalopathy (evidenced by confusion, asterixis, significant sleep disturbance, or hypothermia less than 36º Celsius)
  • No hyponatremia < 130 mEq/L
  • No portal hypertension with bleeding esophageal or gastric varices within the past 3 months

Renal

  • Creatinine ≤ 2 mg/dL

Cardiovascular

  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia

Gastrointestinal

  • No gastrointestinal tract disease resulting in an inability to take oral medication or requirement for IV alimentation
  • No active peptic ulcer disease

Ophthalmic

  • No abnormalities of the cornea (e.g., dry eye syndrome or Sjögren's syndrome)
  • No congenital abnormality (e.g., Fuch's dystrophy)

Other

  • No significant traumatic injury within the past 21 days
  • No other uncontrolled concurrent illness that would preclude study participation
  • No ongoing or active infection
  • No psychiatric illness or social situation that would preclude study compliance
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • See Disease Characteristics
  • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered

Endocrine therapy

  • Not specified

Radiotherapy

  • At least 4 weeks since prior radiotherapy and recovered

Surgery

  • No prior surgical therapy affecting absorption
  • At least 21 days since prior major surgery

Other

  • At least 4 weeks since any other prior agents and recovered
  • No prior epidermal growth factor-receptor targeting therapies
  • No other concurrent investigational agents
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00047346

Locations
United States, Texas
M.D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Study Chair: James L. Abbruzzese, MD M.D. Anderson Cancer Center
  More Information

Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

Study ID Numbers: CDR0000257666, MDA-ID-01510, NCI-5349
Study First Received: October 3, 2002
Last Updated: July 23, 2008
ClinicalTrials.gov Identifier: NCT00047346  
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
recurrent adult primary liver cancer
localized unresectable adult primary liver cancer
advanced adult primary liver cancer
adult primary hepatocellular carcinoma

Study placed in the following topic categories:
Erlotinib
Liver Diseases
Digestive System Neoplasms
Carcinoma, Hepatocellular
Liver neoplasms
Recurrence
Carcinoma
Liver Neoplasms
Signs and Symptoms
Digestive System Diseases
Gastrointestinal Neoplasms
Adenocarcinoma
Neoplasms, Glandular and Epithelial
Hepatocellular carcinoma

Additional relevant MeSH terms:
Neoplasms
Neoplasms by Site
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Protein Kinase Inhibitors
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 15, 2009