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Erlotinib in Treating Patients With Unresectable Liver Cancer and Liver Dysfunction

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00047346
First received: October 3, 2002
Last updated: January 22, 2013
Last verified: January 2013
  Purpose

Phase I trial to study the effectiveness of erlotinib in treating patients who have unresectable liver cancer and liver dysfunction. Biological therapies such as erlotinib may interfere with the growth of tumor cells and slow the growth of the tumor


Condition Intervention Phase
Adult Primary Hepatocellular Carcinoma
Advanced Adult Primary Liver Cancer
Localized Unresectable Adult Primary Liver Cancer
Recurrent Adult Primary Liver Cancer
Drug: erlotinib hydrochloride
Other: pharmacological study
Other: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: 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

Resource links provided by NLM:


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 [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
  • Pharmacokinetic (PK) and pharmacodynamic profile, as measured by Cmax, Tmax, AUC0-24, AUC0-infinity, Cl/F, T1/2, accumulation ratio, and Cssmin [ Time Frame: Days 8-28 ] [ Designated as safety issue: No ]
    PK parameters characterized by use of descriptive statistics. Nonparametric statistical test for several unrelated (Kruskal-Wallis ANOVA) or related (Wilcoxon matched-pairs signed-rank test) parameters used. Relationships between drug dose and indices that reflect drug exposure (Cmax, AUC, Cssmin) evaluated with Kruskal-Wallis one-way ANOVA test. Extent of drug exposure (Cmax, AUC, Cssmin) compared among patients with various grades of toxicity using nonparametric statistical tests for two (Mann-Whitney U test) or several (Kruskal-Wallis one-way ANOVA) independent samples.


Secondary Outcome Measures:
  • Objective response rates (partial, complete, stable disease), as measured by CT scans using RECIST criteria [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Response rates will be calculated as a proportion of the number of patients who are evaluable using 95% confidence intervals.


Enrollment: 24
Study Start Date: August 2002
Primary Completion Date: December 2005 (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.

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.

Drug: erlotinib hydrochloride
Given PO
Other Names:
  • CP-358,774
  • erlotinib
  • OSI-774
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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.

  Eligibility

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

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 months
  • 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 recovered
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00047346

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: NCT00047346     History of Changes
Other Study ID Numbers: NCI-2012-02499, ID01-510, U01CA062461, CDR0000257666
Study First Received: October 3, 2002
Last Updated: January 22, 2013
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on November 27, 2014