Advanced Hepatocellular Carcinoma MedDRA version: 14.1 Level: LLT Classification code 10019829 Term: Hepatocellular carcinoma recurrent System Organ Class: 100000004864
Conditions
Interventions
Product Name: ADI-PEG 20
Product Code: ADI-PEG 20
Pharmaceutical Form: Solution for injection
INN or Proposed INN: PEGylated Arginine Deiminase
Sponsors
Polaris Group
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Prior diagnosis of HCC confirmed histologically or cytologically. 2. Prior treatment with at least 1 systemic agent, with documented PD after systemic agent(s), or AEs associated with prior systemic agent(s) that resulted in discontinuance of that agent(s). Failure is defined as having progressed radiographically on, or been intolerant to prior systemic therapy. Intolerance is defined as discontinuation due to an AE(s) on prior systemic therapy that was unacceptable to the treating physician and / or patient, with or without dose interruption and modification. For sorafenib or any other systemic antineoplastic agent, failure requires at least 14 days of treatment for the agent that defines failure, except for a subject that has a severe allergic reaction to the prior systemic agent at any time, even less than 14 days of treatment of that agent and thus it would be imprudent to re-challenge them with that agent. 3. Measurable disease using RECIST 1.1 criteria (Appendix A). At least 1 measurable lesion must be present. Subjects who have received local-regional therapy such as (but not limited to) chemoembolization, embolization, cryoablation, hepatic artery therapy, percutaneous ethanol injection, radiation therapy, radiofrequency ablation or surgery are eligible, provided that they have either a target lesion which has not been treated with local therapy and/or the target lesion(s) within the field of the local regional therapy has shown an increase of = 20% in size. Local-regional therapy must be completed at least 4 weeks prior to the baseline CT scan. Local therapies including chemoembolization do not count as prior systemic therapy. 4. Cirrhotic status of Child-Pugh grade A and B7. Child-Pugh status should be determined based on clinical findings and laboratory data during the screening period (Appendix C). Subjects on anti-coagulants are to receive only 1 point for their INR status. 5. Expected survival of at least 3 months. 6. Age = 18 years. 7. No prior systemic treatment for HCC in the last 2 weeks prior to first dose of study drug or placebo. 8. Fully recovered from any prior major surgery and none within 2 weeks prior to first dose of study drug or placebo. Liver biopsy for HCC confirmation is allowed. 9. Female subjects of childbearing age and male subjects must be asked to use appropriate contraception for both the male and female for the duration of the study. Subjects must agree to use two forms of contraception or agree to refrain from intercourse for the duration of the study. Females must not be pregnant at the start of the study, and a serum human chorionic gonadotropin (HCG) pregnancy test must be negative before entry into the study. 10. Informed consent must be obtained prior to study initiation. 11. No concurrent investigational studies are allowed. 12. Total bilirubin 1,500/µL. 15. Platelets >50,000/µL. 16. Serum uric acid = 8 mg/dL (with or without medication control). 17. Serum creatinine = 1.5 x the upper limit of normal ran
Exclusion criteria
Exclusion criteria: 1. Candidate for potential curative therapies (i.e., resection or transplantation) or loco-regional approaches (i.e., ablation, embolization). 2. Prior allograft transplantation including liver transplantation. 3. Significant cardiac disease (New York Heart Association Class III or IV; Appendix D). 4. Serious infection requiring treatment with systemically administered antibiotics. 5. Pregnancy or lactation. 6. Expected non-compliance. 7. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association Class III or IV), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness or social situations that would limit compliance with study requirements. 8. Subjects who have had any anticancer treatment within 2 weeks prior to first dose of study drug or placebo. 9. Subjects who have not fully recovered from toxicities associated with previous HCC loco-regional or systemic therapies. 10. 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. 11. Subjects who had been treated with ADI-PEG 20 previously. 12. Allergy to pegylated products. 13. History of seizure disorder. 14. Bleeding esophageal or gastric varices within the prior three months, except if banded or treated. 15. Subjects known to be HIV positive. 16. Uncontrolled ascites (defined as not easily controlled with diuretic treatment). 17. 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. 18. Use of traditional medicines approved by local authorities, including but not limited to Chinese herbs within 2 weeks prior to the first dose of study drug or placebo. 19. Eastern Cooperative Oncology Group (ECOG) performance status > 2.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: OS is assessed weekly while patients are receiving treatment and then monthly thereafter.;Main Objective: To assess overall survival; Secondary Objective: - Assessment of safety and tolerability - Assessment of progression-free survival (PFS), tumor response rate by RECIST (1.1) criteria and time to progression (TTP) ; Primary end point(s): Overall survival will be summarized using the Kaplan-Meier method. Point estimates (25th, 50th, and 75th percentiles) along with 95% confidence intervals will be provided by treatment group. Survival estimates will also be shown graphically for each treatment group. Treatments will be compared using a stratified log-rank test (stratified by the four levels of the region – sorafenib treatment status variable). | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Secondary endpoints are assessed every 8 weeks based on CT/MRI scans. Surgical resection will be assessed whenever it occurs.;Secondary end point(s): The secondary efficacy variables are PFS, objective response rate, duration of objective response, tumor response at each visit, time to tumor progression, disease control rate at each visit, and the occurrence of surgical resections. | — |
Countries
China, Italy, Korea, Republic of, Taiwan, United Kingdom, United States
Contacts
Public ContactClinical Trial Information Desk
Polaris Group
Outcome results
None listed