Safety and Tolerability of I.V. Infusion of MB07133 in Patients With Unresectable Hepatocellular Carcinoma

August 10, 2011 updated by: Ligand Pharmaceuticals

A Phase 1/2 Open-Label Study to Assess the Safety, Tolerability, and Pharmacokinetics of Intravenous Infusion of MB07133 in Subjects With Unresectable Hepatocellular Carcinoma and Child-Pugh Class A Liver Function

Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver. MB07133 is being developed for the treatment of inoperable HCC, using a platform technology known as HepDirectTM, which enables drugs to be targeted specifically to the liver. The objective for this study is to determine the safety and tolerability of MB07133.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

To determine the maximum tolerated dose of MB07133 when administered as a 7-day continuous i.v. To characterize the safety profile and the pharmacokinetics of MB07133 and metabolites during and after continuous infusion. To determine the effect of MB07133 on hepatocellular carcinoma (HCC) tumor size.

Study Type

Interventional

Enrollment (Actual)

28

Phase

  • Phase 2
  • Phase 1

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

  • Hong Kong
      • Shatin, New Territories, Hong Kong
        • Prince of Wales Hospital - Comprehensive Cancer Trial Unit
  • Taiwan
    • Nei Hu District
      • Taipei, Nei Hu District, Taiwan, 114
        • Tri-Services General Hospital
    • Taoyuan County
      • Taipei, Taoyuan County, Taiwan, 333
        • Chang-Gung Memorial Hospital
  • United States
    • California
      • Orange, California, United States, 92868
        • University of California at Irvine

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:

  • Patients with a diagnosis of local unresectable HCC confirmed by histology using fine needle aspirate (FNA) or liver biopsy. "Local" is defined as disease either restricted to the liver or contiguous with the liver and no identifiable extrahepatic disease.
  • Patients with Child-Pugh Class A liver function. For purposes of this trial, an eligible patient must not have Encephalopathy or Ascites and the total Child-Pugh score cannot be greater than 6 at baseline
  • Males or females 18 years of age or older
  • Ability to provide written informed consent before initiation of any study-related procedures and ability, in the opinion of the Principal Investigator, to comply with all the requirements of the study
  • Male and female subjects who are surgically sterile, who remain abstinent, or who agree to practice double barrier forms of birth control from screening through 30 days (females) and 90 days (males), from the last dose of study medication

Exclusion Criteria:

  • History of or presence of clinically significant acute or unstable cardiovascular, cerebrovascular (stroke), renal, GI, pulmonary, immunological (with the exception of the presence of hepatitis B virus [HBV], HCV hepatitis, or cirrhosis), endocrine, or central nervous system disorders
  • Patient has a history of cancer other than hepatocellular (excluding resected basal cell carcinoma; or curatively resected stage 1 or less cervical cancer if disease free for 5 years or more).
  • Patients with distant metastasis or extrahepatic disease
  • An Eastern Cooperative Oncology Group (ECOG) performance status score of greater than or equal to 2
  • Current encephalopathy or current treatment for encephalopathy
  • History of drug or alcohol abuse within 6 months before screening
  • History of, or current clinically significant mental disorder or an antagonistic personality that compromises the validity of the informed consent
  • A documented variceal hemorrhage within 4 months of screening
  • Neutrophil count less than or equal to 1,500/mm3, platelet count less than or equal to 100,000/mm3, hemoglobin less than or equal to 8.5 g/dL, or a Prothrombin Time (INR) greater than 1.3 (vitamin K supplementation allowed)
  • Serum creatinine greater than 1.1 times the upper limit of normal
  • History of human immunodeficiency virus or acquired immune deficiency syndrome
  • Use of an investigational drug or product or participation in a drug study within 30 days before dosing
  • Liver function defined as: serum bilirubin greater than 1.5 times the upper limit of normal or an aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 5 times upper limit of normal, or serum albumin less than 3.2 g/dL
  • History of gout or abnormal uric acid metabolism
  • The clinical presence of ascites
  • Treatment of HCC within 30 days of screening by chemotherapy or treatment of the target lesion(s) by chemoembolization, PEI, or surgery
  • Radiofrequency ("RF") ablation of the target lesion(s) within 60 days of screening
  • Subjects with a life expectancy of less than 12 weeks
  • Subjects having received an organ transplant
  • Subjects currently receiving coumadin or heparin
  • Pregnant or nursing women

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: NON_RANDOMIZED
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: MB07133 Dose Level 1
7-day continuous infusion in 28-day cycles
Drug: MB07133 300mg/m2/day
7-day continuous infusion in 28-day cycles
EXPERIMENTAL: MB07133 Dose Level 2
7-day continuous infusion in 28-day cycles
Drug: MB07133 600 mg/m2/day
7-day continuous infusion in 28-day cycles
EXPERIMENTAL: MB07133 Dose Level 3
7-day continuous infusion in 28-day cycles
Drug: MB07133 1200 mg/m2/day
7-day continuous infusion in 28-day cycles
EXPERIMENTAL: MB07133 Dose Level 4
7-day continuous infusion in 28-day cycles
Drug: MB07133 1800 mg/m2/day
7-day continuous infusion in 28-day cycles
EXPERIMENTAL: MB07133 Dose Level 5
7-day continuous infusion in 28-day cycles
Drug: MB07133 2400 mg/m2/day
7-day continuous infusion in 28-day cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety and tolerability
Time Frame: 7-day continuous infusion every 28-days as tolerated
To determine the dose-limiting toxicities (DLT) of MB07133; To determine the maximum-tolerated continuous infusion dose (MTD) of MB07133
7-day continuous infusion every 28-days as tolerated

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determine effect of MB07133 on tumor size
Time Frame: 28 day cycles
To determine the effect on HCC tumor size by using CT scanning, alpha-fetoprotein (AFP) concentration, and performance status.
28 day cycles

Collaborators and Investigators

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

Sponsor

Ligand Pharmaceuticals

Investigators

  • Study Director: Isabela Niculae, MPH, Metabasis Therapeutics, Inc.

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

September 1, 2003

Primary Completion (ACTUAL)

July 1, 2007

Study Registration Dates

First Submitted

December 3, 2003

First Submitted That Met QC Criteria

December 4, 2003

First Posted (ESTIMATE)

December 5, 2003

Study Record Updates

Last Update Posted (ESTIMATE)

August 12, 2011

Last Update Submitted That Met QC Criteria

August 10, 2011

Last Verified

August 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HCC-101

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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