Safety and Tolerability of I.V. Infusion of MB07133 in Patients With Unresectable Hepatocellular Carcinoma - Full Text View

Sponsor:	Ligand Pharmaceuticals
Information provided by:	Ligand Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00073736

Purpose

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.

Condition	Intervention	Phase
Hepatocellular Carcinoma	Drug: MB07133 300mg/m2/day Drug: MB07133 600 mg/m2/day Drug: MB07133 1200 mg/m2/day Drug: MB07133 1800 mg/m2/day Drug: MB07133 2400 mg/m2/day	Phase I Phase II

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	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

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: MB-07133

U.S. FDA Resources

Further study details as provided by Ligand Pharmaceuticals:

Primary Outcome Measures:

Safety and tolerability [ Time Frame: 7-day continuous infusion every 28-days as tolerated ] [ Designated as safety issue: Yes ]
To determine the dose-limiting toxicities (DLT) of MB07133; To determine the maximum-tolerated continuous infusion dose (MTD) of MB07133

Secondary Outcome Measures:

Determine effect of MB07133 on tumor size [ Time Frame: 28 day cycles ] [ Designated as safety issue: No ]
To determine the effect on HCC tumor size by using CT scanning, alpha-fetoprotein (AFP) concentration, and performance status.

Enrollment:	28
Study Start Date:	September 2003
Primary Completion Date:	July 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

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.

Eligibility

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

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00073736

Locations

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

Sponsors and Collaborators

Ligand Pharmaceuticals

Investigators

Study Director:

Isabela Niculae, MPH

Metabasis Therapeutics, Inc.

More Information

No publications provided

Responsible Party:	Director, Project Management, Ligand Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00073736 History of Changes
Other Study ID Numbers:	HCC-101
Study First Received:	December 3, 2003
Last Updated:	August 10, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Ligand Pharmaceuticals:

Hepatocellular
Carcinoma
Liver
Cancer

Additional relevant MeSH terms:

Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma

Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases

ClinicalTrials.gov processed this record on February 12, 2012