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

This study has been terminated.
(Administratively complete.)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00047333
First received: October 3, 2002
Last updated: January 22, 2013
Last verified: January 2013
  Purpose

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


Condition Intervention Phase
Adult Primary Hepatocellular Carcinoma
Advanced Adult Primary Liver Cancer
Localized Unresectable Adult Primary Liver Cancer
Drug: erlotinib hydrochloride
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Open-Label Study Of OSI-774 (NSC 718781) In Unresectable Hepatocellular Carcinoma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Progression-free survival [ Time Frame: Time from initiation of therapy until documented disease progression, assessed at 16 weeks ] [ Designated as safety issue: No ]
    Summarized by Kaplan-Meier curves, from which medians and progression-free survival can be attained.


Secondary Outcome Measures:
  • Objective response rate [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    Summarized by estimates and standard errors.

  • Rate of stable disease [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    Summarized by estimates and standard errors.

  • Duration of stable disease [ Time Frame: From the start of the treatment until the criteria for progression are met, assessed up to 4 years ] [ Designated as safety issue: No ]
    Summarized by Kaplan-Meier curves, from which medians and overall duration of stable disease can be attained.

  • Time to progression [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    Summarized by Kaplan-Meier curves, from which medians and time to progression can be attained.

  • Overall survival [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    Summarized by Kaplan-Meier curves, from which medians and overall survival can be attained.


Enrollment: 80
Study Start Date: August 2002
Primary Completion Date: January 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (erlotinib hydrochloride)
Patients receive oral erlotinib once daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: erlotinib hydrochloride
Given PO
Other Names:
  • CP-358,774
  • erlotinib
  • OSI-774
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

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.

  Eligibility

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

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00047333

Locations
United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Investigators
Principal Investigator: Melanie Thomas M.D. Anderson Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00047333     History of Changes
Other Study ID Numbers: NCI-2012-02498, ID02-008, CDR0000257665
Study First Received: October 3, 2002
Last Updated: January 22, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Liver Neoplasms
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Adenocarcinoma
Erlotinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014