Erlotinib in Treating Patients With Liver Cancer That Cannot be Surgically Removed

January 22, 2013 updated by: National Cancer Institute (NCI)

A Phase 2 Open-Label Study Of OSI-774 (NSC 718781) In Unresectable Hepatocellular Carcinoma

Phase II trial to study the effectiveness of erlotinib in treating patients who have liver cancer that cannot be surgically removed. Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth

Study Overview

Detailed Description

PRIMARY OBJECTIVES:

I. To assess progression-free survival (PFS) measured at 16 weeks following initiation of once daily continuous oral therapy with OSI-774 in patients with unresectable hepatocellular carcinoma.

SECONDARY OBJECTIVES:

I. To assess objective response rate, rate and duration of stable disease, time to progression, median and overall survival in this patient population, and any changes in tumor perfusion based on functional CT imaging.

II. To correlate response with patient characteristics including: age, disease stage (TNM, Okuda [6]), viral hepatitis status, pathologic grade of cirrhosis, Childs-Pugh status, Performance Status, serum values of: alpha feto-protein, bilirubin, transaminases, albumin; EGFR expression score by IHC; and development of skin rash during therapy.

III. To determine the pharmacokinetic and pharmacodynamic profile of OSI-774 in this patient population.

IV. To determine the safety and tolerability of OSI-774 in this patient population.

OUTLINE: Patients are stratified according to epidermal growth factor receptor expression (low, 0-1+ vs high, 2-3+).

Patients receive oral erlotinib once daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months.

Study Type

Interventional

Enrollment (Actual)

80

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Texas
      • Houston, Texas, United States, 77030
        • M D Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically confirmed hepatocellular carcinoma (HCC)not amenable to curative resection

    • No fibrolamellar HCC
  • No prior therapy for HCC, including systemic chemotherapy, hepatic arterial infusion of chemotherapeutic agents or irradiated microspheres, and epidermal growth factor receptor-targeting agents

    • The following prior therapies are allowed provided previously treated lesions remain separate from those to be evaluated in present study

      • Surgery
      • Liver-directed therapy (e.g., radiofrequency ablation, transarterial embolization/chemoembolization, or percutaneous ethanol injection)
  • At least 1 unidimensionally measurable lesion

    • At least 20 mm by conventional techniques
  • Must have paraffin tissue block or unstained slides from biopsy or surgical specimen
  • 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 at least 1,500/mm^3
  • Platelet count at least 60,000/mm^3
  • Hemoglobin at least 10 g/dL
  • Bilirubin no greater than 1.8 mg/dL
  • Albumin at least 2.5 g/dL
  • AST/ALT no greater than 5 times upper limit of normal
  • PT no greater than 1-3 seconds over normal
  • No decompensated liver disease
  • No jaundice
  • No portosystemic encephalopathy (evidenced by confusion, asterixis, significant sleep disturbance, or hypothermia less than 36º Celsius)
  • No hyponatremia with sodium less than 125 mEq/L
  • No portal hypertension with bleeding esophageal or gastric varices within the past 3 months
  • Creatinine no greater than 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 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
  • No other malignancy within the past 5 years except nonmelanoma skin cancer
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No prior surgical therapy affecting absorption
  • More than 30 days since prior investigational agents
  • No concurrent commercial or other investigational anticancer agents or therapies
  • No concurrent combination antiretroviral therapy for HIV-positive patients

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (erlotinib hydrochloride)
Patients receive oral erlotinib once daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Correlative studies
Correlative studies
Other Names:
  • pharmacological studies
Given PO
Other Names:
  • OSI-774
  • erlotinib
  • CP-358,774

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival
Time Frame: Time from initiation of therapy until documented disease progression, assessed at 16 weeks
Summarized by Kaplan-Meier curves, from which medians and progression-free survival can be attained.
Time from initiation of therapy until documented disease progression, assessed at 16 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response rate
Time Frame: Up to 4 years
Summarized by estimates and standard errors.
Up to 4 years
Rate of stable disease
Time Frame: Up to 4 years
Summarized by estimates and standard errors.
Up to 4 years
Duration of stable disease
Time Frame: From the start of the treatment until the criteria for progression are met, assessed up to 4 years
Summarized by Kaplan-Meier curves, from which medians and overall duration of stable disease can be attained.
From the start of the treatment until the criteria for progression are met, assessed up to 4 years
Time to progression
Time Frame: Up to 4 years
Summarized by Kaplan-Meier curves, from which medians and time to progression can be attained.
Up to 4 years
Overall survival
Time Frame: Up to 4 years
Summarized by Kaplan-Meier curves, from which medians and overall survival can be attained.
Up to 4 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Melanie Thomas, M.D. Anderson Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2002

Primary Completion (Actual)

January 1, 2006

Study Registration Dates

First Submitted

October 3, 2002

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

January 23, 2013

Last Update Submitted That Met QC Criteria

January 22, 2013

Last Verified

January 1, 2013

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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