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

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

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.

Study Overview

• Status: Completed
• Conditions: Unresectable Hepatocellular Carcinoma
• Intervention / Treatment: Drug: ADI-PEG 20; Drug: Transarterial chemoembolization

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Taiwan
  • Taichung City, Taiwan
    • CMUH
  • Taipei, Taiwan
    • National Taiwan University Hospital
  • Taipei City, Taiwan
    • TP-VGH
  • Taoyuan, Taiwan
    • CGMH-LK

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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).
2. 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.
3. Not a candidate for surgical resection or ablation of the tumor.
4. 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.
5. The subject must have received no more than 2 TACE (n≤ 2) or the previous TACE was performed longer than 2 months before enrollment.
6. Local therapy must have been completed at least 4 weeks before baseline scan.
7. Measurable disease using mRECIST criteria (Appendix A) and RECIST1.1 (Appendix B) criteria. At least 1 measurable lesion must be present.
8. Barcelona Clinic Liver Cancer (BCLC) staging classification B (intermediate stage) (Appendix C).

Exclusion Criteria:

1. 1. Candidate for potential curative therapies (i.e., resection or transplantation).
2. Prior allograft transplantation including liver transplantation.
3. Significant cardiac disease (New York Heart Association Class III or IV; Appendix F).
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 week 1 visit.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: ADI-PEG 20 + TACE; ADI-PEG 20 plus concurrent transarterial chemoembolization	Drug: ADI-PEG 20; Other Names: arginine deiminase formulated with polyethylene glycol; Drug: Transarterial chemoembolization; Other Names: TACE
ACTIVE_COMPARATOR: Transarterial chemoembolization (TACE); transarterial chemoembolization alone	Drug: Transarterial chemoembolization; Other Names: TACE

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Polaris Group
• Investigators: Principal Investigator: Pei-Jer Chen, MD, PhD, National Taiwan University Hospital Taipei, Taiwan

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 15, 2014
• Primary Completion (ACTUAL): July 31, 2016
• Study Completion (ACTUAL): November 1, 2017

Study Registration Dates

• First Submitted: November 27, 2013
• First Submitted That Met QC Criteria: December 4, 2013
• First Posted (ESTIMATE): December 9, 2013

Study Record Updates

• Last Update Posted (ACTUAL): September 4, 2018
• Last Update Submitted That Met QC Criteria: August 30, 2018
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: Liver Cancer; Unresectable Hepatocellular Carcinoma; ADI-PEG 20; ADI
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: POLARIS2013-003