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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

Phase 1
18 Years
Not Enrolling
Adult Primary Hepatocellular Carcinoma, Advanced Adult Primary Liver Cancer, Localized Unresectable Adult Primary Liver Cancer, Recurrent Adult Primary Liver Cancer

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Trial Information

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


I. Establish the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of OSI-774 in
patients with unresectable hepatocellular carcinoma (HCC) with moderate liver dysfunction.

II. Establish the pharmacokinetic and pharmacodynamic profile of OSI-774 in HCC patients
with moderate liver dysfunction.


I. Assess possible anti-tumor effects of OSI-774 in patients with advanced hepatocellular
carcinoma in terms of partial response (PR) and complete response (CR) as assessed by tumor
shrinkage by RECIST criteria.

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.

Inclusion Criteria:

- 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)

- Performance status - ECOG 0-2

- At least 16 weeks

- Granulocyte count ≥ 1,500/mm^3

- Platelet count ≥ 60,000/mm^3

- Hemoglobin ≥ 10 g/dL

- 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

- Creatinine ≤ 2 mg/dL

- No symptomatic congestive heart failure

- No unstable angina pectoris

- No cardiac arrhythmia

- No gastrointestinal tract disease resulting in an inability to take oral medication
or requirement for IV alimentation

- No active peptic ulcer disease

- No abnormalities of the cornea (e.g., dry eye syndrome or Sjögren's syndrome)

- No congenital abnormality (e.g., Fuch's dystrophy)

- 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

- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and

- At least 4 weeks since prior radiotherapy and recovered

- No prior surgical therapy affecting absorption

- At least 21 days since prior major surgery

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Dose-limiting toxicity and maximum tolerated dose as measured by NCI CTCAE v3.0 continuously

Outcome Time Frame:

28 days

Safety Issue:


Principal Investigator

Melanie Thomas

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

August 2002

Completion Date:

Related Keywords:

  • Adult Primary Hepatocellular Carcinoma
  • Advanced Adult Primary Liver Cancer
  • Localized Unresectable Adult Primary Liver Cancer
  • Recurrent Adult Primary Liver Cancer
  • Carcinoma
  • Liver Neoplasms
  • Liver Diseases
  • Carcinoma, Hepatocellular



M D Anderson Cancer Center Houston, Texas  77030