Hepatocellular CarcinomaPhase 3NCT05317819
Study of ADI-PEG 20 Versus Placebo in Subjects With High Arginine Level and Unresectable Hepatocellular Carcinoma
A Phase 3 study testing ADI-PEG20 in people with Hepatocellular Carcinoma and Advanced Hepatocellular Carcinoma, run by Polaris Group at 11 sites in 2 countries.
Trial summary
Evaluate efficacy and safety of ADI-PEG 20 in patients with high-argininephenotypic and HCC Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Hepatocellular Carcinoma, Advanced Hepatocellular Carcinoma
- What is being tested?
- ADI-PEG20
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 300 participants
- Where
- 11 sitesin 2 countries
- Study dates
- 14 Mar 2022to Dec 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Prior diagnosis of HCC confirmed by radiology, histology, or cytology.
- Prior treatment with at least 1 systemic agent for Child-Pugh A subjects. However, Child-Pugh B7 subjects without prior systemic treatment may be enrolled, if they are not eligible for any approved systemic therapies (e.g., due to financial factors).
- Plasma arginine ≥ 78 μM at pre-screening visit.
- Measurable disease using RECIST 1.1 (Appendix A). At least 1 measurable lesion must be present. Subjects who have received local-regional therapies 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.
- Child-Pugh (cirrhosis status) score class A-B7 (Appendix C).
- Barcelona Cancer of the Liver (BCLC) stage C (Appendix B)
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- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrollment (Appendix D).
- Expected survival of at least 3 months.
- Age >18 years.
- Fully recovered from prior surgery, radiation, or chemotherapy, and none within 2 weeks prior to week 1 visit. Liver biopsy for HCC confirmation is allowed.
- Female subjects and male subjects must be asked to use appropriate contraception for both the male and female for the duration of the study and for 35 days after last dose of ADI-PEG 20/placebo. Male partners of female subjects and female partners of male subjects must agree to use two forms of contraception or agree to refrain from intercourse for the duration of the study if they are of childbearing potential. Females of childbearing potential 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. If positive HCG pregnancy test, further evaluation to rule out pregnancy must be performed according to GCP before this subject is deemed eligible. Females not of childbearing potential must be post-menopausal (defined as cessation of regular menstrual period for at least 12 months).
- Informed consent must be obtained prior to study initiation.
- No concurrent investigational studies are allowed.
- Total bilirubin < 3.0 mg/dL and no evidence of bile obstruction.
- Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤5 x upper limit of normal range.
- Serum albumin level ≥ 3.0 g/dl.
- Prothrombin time (PT)-international normalized ratio (INR): PT <3 seconds above control or INR <1.7.
- Absolute neutrophil count (ANC) >1,500/µL.
- Platelets >50,000/µL.
- Serum uric acid ≤ 8 mg/dL (with or without medication control).
- Serum creatinine ≤ 1.5 x the upper limit of normal range, or, if serum creatinine >1.5 x the upper limit of normal range, then the creatinine clearance must be ≥ 40 mL/min.
- Subjects with active hepatitis B or C on anti-viremic compounds may remain on such treatment, except for interferon.
- Encephalopathy - none or mild (grade 1 or 2, by Child-Pugh classification); lactulose of other supportive care allowed.
- Ascites - absent or slight (by Child-Pugh classification); diuretic therapy allowed.
Who cannot join
- Candidate for potential curative therapies (i.e., resection or transplantation) or eligible for approved systemic therapies according to the labeling of such drugs.
- Prior allograft transplantation including liver transplantation.
- Subjects who have not fully recovered from toxicities associated with previous HCC loco-regional or systemic therapies, except for Grade 1 alopecia.
- Serious infection requiring treatment with intravenous, systemically administered antibiotics at the time of study entrance, or an infection requiring systemic antibiotic therapy within 7 days prior to the first dose of study treatment.
- Pregnancy or lactation.
- Expected non-compliance.
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- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association Class III or IV), cardiac arrhythmia, or psychiatric illness, social situations that would limit compliance with study requirements.
- Subjects with history of another primary cancer, including co-existent second malignancy, 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 or in the opinion of the investigator will not affect patient outcome.
- Subjects who had been treated with ADI-PEG 20 previously.
- History of uncontrolled seizure disorder not related to underlying cancer.
- Allergy to pegylated compounds.
- Allergy to E. coli drug products (such as GMCSF).
- Bleeding esophageal or gastric varices within the prior three months, except if banded or treated.
- 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 week 1 visit.
- Eastern Cooperative Oncology Group (ECOG) performance status ≥ 2.
Trial locations and contacts
11 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
11 sites in 2 countries
Taiwan8 sites, 8 recruiting
- Recruiting
Changhua Christian Hospital (CCH)
Changhua, 500
Yu-Chun Hsu, 886-4-7238595 ext. 5507, 77149@cch.org.tw
- Recruiting
Ditmanson Medical Foundation Chiayi Christian Hospital (CYCH)
Chiayi City, 600
Chu-Kuang Chou, 886-5-2765041 ext. 8636, vacinu@gmail.com
- Recruiting
Chang Gung Medical Foundation-Chia-Yi (CGMF-CY)
Chiayi City, 613
Te-Sheng Chang, 886-5-3621000 ext. 2242, cgmh3621@cgmh.org.tw
- Recruiting
Kaohsiung Medical University Chung-Ho Memorial Hospital (KMUH)
Kaohsiung City, 807
Ming-Lung Yu, 886-7-3121101 ext. .7475, fish6069@gmail.com
- Recruiting
Chang Gung Medical Foundation-Kaohsiung(CGMF-KS)
Kaohsiung City, 833
Sheng-Nan Lu, 886-7-7317123 ext. 8301, juten@ms17.hinet.net
- Recruiting
Chi Mei Medical Center (CMMC-YK)
Tainan, 710
Hung-Chang Wu, 886-6-2812811 ext. 53571, hungchang.wu@gmail.com
- Recruiting
Chi Mei Hospital, Liouying (CMMC-LY)
Tainan, 736
Shang-Wen Chen, 886-6-6226999 ext. 73132, saintwin.chen@gmail.com
- Recruiting
Chang Gung Medical Foundation-Linkou (CGMF-LK)
Taoyuan, 333
Chau-Ting Yeh, 886-3-3281200 ext. 8121, chauting@cgmh.org.tw
Vietnam3 sites, 3 recruiting
- Not yet recruiting
K Hospital
Hà Nội, 100000
Tran Thang, (+84)913064307, tranthangncc@gmail.com
Dao Van Tu, (+84)985696908, vantu.dao@nci.vn
- Not yet recruiting
Bach Mai Hospital
Hanoi, 100000
Nguyen Quang Hung, (+84)909572686, nguyenquanghungbvbm2013@gmail.com
- Not yet recruiting
Hue Central Hospital
Huế, 49000
Phan Hai Thanh, (+84)903591080, phanhaithanhvn@yahoo.com
About this study
Official title: A Randomized, Double-Blind, Multi-Center Study of ADI-PEG 20 Versus Placebo in Subjects With High Arginine Level and Unresectable Hepatocellular Carcinoma
Evaluate efficacy and safety of ADI-PEG 20 in patients with high-argininephenotypic and HCC
Read the detailed description
Safety will be evaluated by laboratory tests, vital sign measurements, physical examinations and subject medical history which will be performed to detect new abnormalities and any deterioration in pre-existing conditions.
Efficacy will be determined by overall survival, progression free survival, pharmacodynamics (peripheral blood arginine and citrulline levels) and immunogenicity (antibodies to ADI-PEG 20).
- Being tested
- ADI-PEG20, Placebo
- Keywords
- Unresectable Hepatocellular Carcinoma, Genotype, Arginine, Arginine Deiminase, ADI-PEG 20, pegargiminase
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ADI-PEG20Drug
Also called pegargiminase
Treatment for hepatocellular carcinoma
PlaceboOther
Treatment for hepatocellular carcinoma
| Study group | Role | What they receive |
|---|---|---|
| Drug: ADI-PEG 20 | Experimental | Dose: 36 mg/m2 given weekly Route of Administration: Intramuscular (IM) Receives: Drug: ADI-PEG20 |
| Drug: Placebo | Placebo comparator | Dose: 36 mg/m2 given weekly Route of Administration: Intramuscular (IM) Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival (OS)
Time from study enrollment to death
Measured: Approximately 18 months
Secondary outcomes (1)
Progression free survival
Time from study enrollment to progressive disease or death
Measured: Approximately 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2022
- Study start14 Mar 2022
- Primary completionSep 2028 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- To evaluate efficacy and safety of ADI-PEG 20 or Placebo in patients with high-arginine-phenotypic and HCC
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Polaris Group
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- John S Bomalaski, Study director, Polaris Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05317819
- Sponsor's protocol ID
- POLARIS2021-001
- Status last verified
- Nov 2025
- First submitted
- 1 Apr 2022
- Last updated
- 18 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Multi-Center Study of ADI-PEG 20 Versus Placebo in Subjects With High Arginine Level and Unresectable Hepatocellular Carcinoma
- ClinicalTrials.gov ID
- NCT05317819
- Acronym / sponsor ID
- POLARIS2021-001
- Keywords
- Unresectable Hepatocellular Carcinoma, Genotype, Arginine, Arginine Deiminase, ADI-PEG 20, pegargiminase
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- Polaris GroupIndustry (pharma, biotech, devices)
- Study start
- 14 Mar 2022 (actual)
- Primary completion
- Sep 2028 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 8 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Evaluate efficacy and safety of ADI-PEG 20 in patients with high-argininephenotypic and HCC
Detailed description
Safety will be evaluated by laboratory tests, vital sign measurements, physical examinations and subject medical history which will be performed to detect new abnormalities and any deterioration in pre-existing conditions.
Efficacy will be determined by overall survival, progression free survival, pharmacodynamics (peripheral blood arginine and citrulline levels) and immunogenicity (antibodies to ADI-PEG 20).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- To evaluate efficacy and safety of ADI-PEG 20 or Placebo in patients with high-arginine-phenotypic and HCC
| Arm | Type | Receives |
|---|---|---|
| Drug: ADI-PEG 20 | Experimental | Drug: ADI-PEG20Dose: 36 mg/m2 given weekly Route of Administration: Intramuscular (IM) |
| Drug: Placebo | Placebo comparator | Other: PlaceboDose: 36 mg/m2 given weekly Route of Administration: Intramuscular (IM) |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Prior diagnosis of HCC confirmed by radiology, histology, or cytology.
- Prior treatment with at least 1 systemic agent for Child-Pugh A subjects. However, Child-Pugh B7 subjects without prior systemic treatment may be enrolled, if they are not eligible for any approved systemic therapies (e.g., due to financial factors).
- Plasma arginine ≥ 78 μM at pre-screening visit.
- Measurable disease using RECIST 1.1 (Appendix A). At least 1 measurable lesion must be present. Subjects who have received local-regional therapies 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.
- Child-Pugh (cirrhosis status) score class A-B7 (Appendix C).
Key exclusion criteria (16 listed)
- Candidate for potential curative therapies (i.e., resection or transplantation) or eligible for approved systemic therapies according to the labeling of such drugs.
- Prior allograft transplantation including liver transplantation.
- Subjects who have not fully recovered from toxicities associated with previous HCC loco-regional or systemic therapies, except for Grade 1 alopecia.
- Serious infection requiring treatment with intravenous, systemically administered antibiotics at the time of study entrance, or an infection requiring systemic antibiotic therapy within 7 days prior to the first dose of study treatment.
- Pregnancy or lactation.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ADI-PEG20Also: pegargiminaseTreatment for hepatocellular carcinoma | Drug | Drug: ADI-PEG 20 |
| PlaceboTreatment for hepatocellular carcinoma | Other | Drug: Placebo |
Primary outcome
Overall Survival (OS)
Time frame: Approximately 18 months
Time from study enrollment to death
1 secondary outcome
Progression free survival
Time frame: Approximately 18 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
John S Bomalaski study director
Polaris Group
11 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing ADI-PEG20 in people with Hepatocellular Carcinoma and Advanced Hepatocellular Carcinoma, run by Polaris Group at 11 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 18 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in Taiwan, Vietnam. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Maureen Liu (+886226562727 ext. 139, mliu@polarispharma.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (OS) (time frame: Approximately 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2025.