Ph 3 ADI-PEG 20 Versus Placebo in Subjects With Advanced Hepatocellular Carcinoma Who Have Failed Prior Systemic Therapy

Phase 3

Completed

• Conditions: Hepatocellular Carcinoma
• Interventions: Drug: ADI-PEG 20 (arginine deiminase formulated with polyethylene glycol); Drug: Placebo; Other: Best Supportive Care

• Registration Number: NCT01287585
• Lead Sponsor: Polaris Group

Brief Summary

This is a study of ADI-PEG 20 (pegylated arginine deiminase), an arginine degrading enzyme versus placebo in patients with hepatocellular carcinoma who have failed prior systemic treatment (chemotherapy). Hepatocellular carcinomas have been found to require arginine, an amino acid. Thus the hypothesis is that by restricting arginine with ADI-PEG 20, the hepatocellular carcinoma cells will starve and die.

Detailed Description

Patients will be randomized 2:1 to study drug versus placebo. Patients will be recruited from North American, Europe and Asia. In addition to overall survival, progression free survival, responses by RECIST 1.1 criteria and time to tumor progression will be calculated. Safety and tolerability will be assessed, as will pharmacodynamics (peripheral blood levels of arginine and citrulline), pharmacokinetics (peripheral blood levels of ADI-PEG 20) and immunogenicity (antibodies to ADI-PEG 20).

Study Timeline

• Study First Submitted: 2011-01-25
• Study First Submitted QC: 2011-01-31
• Study First Posted: 2011-02-01
• Study Start: 2011-07
• Primary Completion: 2015-07
• Study Completion: 2015-07
• Status Verified: 2016-08
• Disposition First Submitted: 2016-08-10
• Disposition First Submitted QC: 2016-08-24
• Disposition First Posted: 2016-08-26
• Last Update Submitted: 2019-08-27
• Last Update Posted: 2019-09-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 636

Inclusion Criteria

• Prior diagnosis of HCC confirmed histologically.
• Prior treatment with at least 1 systemic agent, with documented progressive disease after systemic agent(s), or adverse event(s)associated with prior systemic agent(s) that resulted in discontinuance of that agent(s).
• Cirrhotic status of Child-Pugh grade B7.
• Expected survival of at least 3 months.
• Adequate hematologic, hepatic, and renal function.

Exclusion Criteria

• Candidate for potential curative therapies (i.e., resection or transplantation) or loco-regional approaches (i.e., ablation, embolization).
• Significant cardiac disease.
• Serious infection requiring treatment with systemically administered antibiotics.
• Pregnancy or lactation.
• Expected non-compliance.
• Uncontrolled intercurrent illness, or psychiatric illness or social situations that would limit compliance with study requirements.
• Subjects who have had any anticancer treatment within 2 weeks prior to entering the study.
• Subjects who have not fully recovered from toxicities associated with previous HCC loco-regional or systemic therapies.
• Subjects with history of another primary cancer, with the exception of: a) curatively resected non-melanoma skin cancer; b) curatively treated cervical carcinoma in situ; or c) other primary solid tumor with no known active disease present in the opinion of the investigator will not affect patient outcome in the setting of current HCC diagnosis.
• Allergy to pegylated products.
• Bleeding esophageal or gastric varices within the prior three months, except if banded or treated.
• Subjects known to be HIV positive.
• Uncontrolled ascites (defined as not easily controlled with diuretic treatment).
• Having received any blood transfusion, blood component preparation, erythropoietin, albumin preparation, or granulocyte colony stimulating factors (G-CSF) within 7 days prior to screening laboratories or after screening laboratories have been obtained until first dose of study drug or placebo.
• Use of traditional medicines approved by local authorities, including but not limited to Chinese herbs within 14 days of first dose of study drug or placebo.
• ECOG performance status > 2.
• Prior allograft,including liver transplant.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Best Supportive Care	an inert treatment with no therapeutic value.
ADI-PEG 20	ADI-PEG 20 (arginine deiminase formulated with polyethylene glycol)	Arginine deiminase formulated with polyethylene glycol.
ADI-PEG 20	Best Supportive Care	Arginine deiminase formulated with polyethylene glycol.
Placebo	Placebo	an inert treatment with no therapeutic value.

Primary Outcome Measures

Name	Time	Method
Overall survival	18 months	Overall survival - until death or study closure.

Secondary Outcome Measures

Name	Time	Method
Safety and tolerability - number of participants with adverse events.	18 months - at anticipated end of study.	In addition to safety and tolerability, progression free survival, response rate using RECIST 1.1 and time to tumor progression will be assessed.

Trial Locations

Locations (73)

University of Alabama; 🇺🇸 Birmingham, Alabama, United States

Southern California Research Center; 🇺🇸 Coronado, California, United States

Catherine Frenette; 🇺🇸 La Jolla, California, United States

Stanford University; 🇺🇸 Palo Alto, California, United States

University of California at San Diego Moores Cancer Center; 🇺🇸 San Diego, California, United States

Pacific Medical Center; 🇺🇸 San Francisco, California, United States

Piedmont Research Institute; 🇺🇸 Atlanta, Georgia, United States

University of Hawaii; 🇺🇸 Honolulu, Hawaii, United States

University of Maryland Greenbaum Cancer Center; 🇺🇸 Baltimore, Maryland, United States

Johns Hopkins University Hospital; 🇺🇸 Baltimore, Maryland, United States

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