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

Ligand Pharmaceuticals

Status and phase

Completed

Phase 2

Phase 1

Conditions

Hepatocellular Carcinoma

Treatments

Drug: MB07133 1200 mg/m2/day

Drug: MB07133 2400 mg/m2/day

Drug: MB07133 600 mg/m2/day

Drug: MB07133 1800 mg/m2/day

Drug: MB07133 300mg/m2/day

Study type

Interventional

Funder types

Industry

Identifiers

NCT00073736

HCC-101

Details and patient eligibility

About

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.

Full 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.

Enrollment

28 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Single Group Assignment

Masking

None (Open label)

28 participants in 5 patient groups

MB07133 Dose Level 1

Experimental group

Description: