Ph 2 Trial of ADI PEG 20 Plus Concurrent Transarterial Chemoembolization (TACE) Vs TACE Alone in Patients With Unresectable Hepatocellular Carcinoma

Study Overview
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Brief Summary
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Certain cancers require the amino acid arginine. Arginine deiminase (ADI) is an enzyme from microbes that degrade arginine. ADI has been formulated with polyethylene glycol and has been used to treat patients that have cancers that require arginine. In this study, the investigators will evaluate the response rate, as determined by the revised International Working Group recommendations.

Official Title
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Randomized, Open Label, Phase 2 Trial of ADI PEG 20 Plus Concurrent Transarterial Chemoembolization (TACE) Versus TACE Alone in Patients With Unresectable Hepatocellular Carcinoma

Conditions
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Unresectable Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: ADI-PEG 20
* Drug: Transarterial chemoembolization


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of HCC confirmed clinically or histologically or cytologically. A clinical diagnosis of HCC, using the 2010 Guideline of the American Association for the Study of Liver Diseases requires the presence of hepatic tumor(s) with image findings (e.g. sonography, CT or MRI) compatible with HCC, and no evidence of other gastrointestinal tumors (Bruix [2011] - Guideline, 2010). Solitary hepatic tumor <8 cm in diameter or multifocal disease as evidenced by CT or MRI scan. Tumor volume ≥50% of liver organ or infiltrating HCC should be excluded. Not a candidate for surgical resection or ablation of the tumor. The target lesion must not have been treated previously with local therapy, including TACE. Prior local therapy (radiofrequency ablation, percutaneous ethanol injection, cryoablation, or surgery) to nontarget lesions is acceptable. The subject must have received no more than 2 TACE (n≤ 2) or the previous TACE was performed longer than 2 months before enrollment. Local therapy must have been completed at least 4 weeks before baseline scan. Measurable disease using mRECIST criteria (Appendix A) and RECIST1.1 (Appendix B) criteria. At least 1 measurable lesion must be present. Barcelona Clinic Liver Cancer (BCLC) staging classification B (intermediate stage) (Appendix C). Exclusion Criteria: 1. Candidate for potential curative therapies (i.e., resection or transplantation). Prior allograft transplantation including liver transplantation. Significant cardiac disease (New York Heart Association Class III or IV; Appendix F). Serious infection requiring treatment with systemically administered antibiotics. Pregnancy or lactation. Expected non-compliance. 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. Subjects who have had any anticancer treatment within 2 weeks prior to week 1 visit.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ADI-PEG 20 + TACE<br>ADI-PEG 20 plus concurrent transarterial chemoembolization | Drug: ADI-PEG 20<br> <br> * Other names: arginine deiminase formulated with polyethylene glycol;Drug: Transarterial chemoembolization<br> <br> * Other names: TACE;|
| Active Comparator: Transarterial chemoembolization (TACE)<br>transarterial chemoembolization alone | Drug: Transarterial chemoembolization<br> <br> * Other names: TACE;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine time to tumor progression (TTP) |  | 2 years estimated - course of study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response rates |  | 2 years estimated - course of study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Unresectable Hepatocellular Carcinoma, Liver Cancer, ADI, ADI-PEG 20