Study of ADI-PEG 20 Versus Placebo in Subjects With High Arginine Level and Unresectable Hepatocellular Carcinoma

July 26, 2023 updated by: Polaris Group

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

300

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Taiwan
      • Changhua, Taiwan, 500
        • Recruiting
        • Changhua Christian Hospital (CCH)
        • Contact:
      • Chiayi City, Taiwan, 613
        • Recruiting
        • Chang Gung Medical Foundation-Chia-Yi (CGMF-CY)
        • Contact:
      • Chiayi City, Taiwan, 600
        • Recruiting
        • Ditmanson Medical Foundation Chiayi Christian Hospital (CYCH)
        • Contact:
      • Kaohsiung, Taiwan, 807
        • Recruiting
        • Kaohsiung Medical University Chung-Ho Memorial Hospital (KMUH)
        • Contact:
      • Kaohsiung, Taiwan, 833
        • Recruiting
        • Chang Gung Medical Foundation-Kaohsiung(CGMF-KS)
        • Contact:
      • Tainan, Taiwan, 710
        • Recruiting
        • Chi Mei Medical Center (CMMC-YK)
        • Contact:
      • Tainan, Taiwan, 736
        • Recruiting
        • Chi Mei Hospital, Liouying (CMMC-LY)
        • Contact:
      • Taipei, Taiwan, 112
        • Recruiting
        • Taipei Veterans General Hospital (TPVGH)
        • Contact:
      • Taoyuan, Taiwan, 333
        • Recruiting
        • Chang Gung Medical Foundation-Linkou (CGMF-LK)
        • Contact:
  • Vietnam
      • Hanoi, Vietnam, 100000
      • Hue, Vietnam, 49000
        • Not yet recruiting
        • Huế Central Hospital
        • Contact:
      • Hà Nội, Vietnam, 100000

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 97 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Prior diagnosis of HCC confirmed by radiology, histology, or cytology.
  2. 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.
  3. Plasma arginine ≥ 84.2 μM at pre-screening visit.
  4. 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.
  5. Child-Pugh (cirrhosis status) score class A-B7 (Appendix C).
  6. Barcelona Cancer of the Liver (BCLC) stage C (Appendix B)
  7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrollment (Appendix D).
  8. Expected survival of at least 3 months.
  9. Age >18 years.
  10. 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.
  11. 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. 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).
  12. Informed consent must be obtained prior to study initiation.
  13. No concurrent investigational studies are allowed.
  14. Total bilirubin < 3.0 mg/dL and no evidence of bile obstruction.
  15. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤5 x upper limit of normal range.
  16. Serum albumin level ≥ 3.0 g/dl.
  17. Prothrombin time (PT)-international normalized ratio (INR): PT <3 seconds above control or INR <1.7.
  18. Absolute neutrophil count (ANC) >1,500/µL.
  19. Platelets >50,000/µL.
  20. Serum uric acid ≤ 8 mg/dL (with or without medication control).
  21. 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.
  22. Subjects with active hepatitis B or C on anti-viremic compounds may remain on such treatment, except for interferon.
  23. Encephalopathy - none or mild (grade 1 or 2, by Child-Pugh classification); lactulose of other supportive care allowed.
  24. Ascites - absent or slight (by Child-Pugh classification); diuretic therapy allowed.

Exclusion Criteria:

  1. Candidate for potential curative therapies (i.e., resection or transplantation) or eligible for approved systemic therapies according to the labeling of such drugs.
  2. Prior allograft transplantation including liver transplantation.
  3. Subjects who have not fully recovered from toxicities associated with previous HCC loco-regional or systemic therapies, except for Grade 1 alopecia.
  4. 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.
  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), cardiac arrhythmia, or psychiatric illness, social situations that would limit compliance with study requirements.
  8. 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.
  9. Subjects who had been treated with ADI-PEG 20 previously.
  10. History of uncontrolled seizure disorder not related to underlying cancer.
  11. Allergy to pegylated compounds.
  12. Allergy to E. coli drug products (such as GMCSF).
  13. Bleeding esophageal or gastric varices within the prior three months, except if banded or treated.
  14. Uncontrolled ascites (defined as not easily controlled with diuretic treatment).
  15. 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.
  16. Eastern Cooperative Oncology Group (ECOG) performance status ≥ 2.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Drug: ADI-PEG 20
Dose: 36 mg/m2 given weekly Route of Administration: Intramuscular (IM)
Drug: ADI-PEG20
Treatment for hepatocellular carcinoma
Other Names:
  • pegargiminase
Placebo Comparator: Drug: Placebo
Dose: 36 mg/m2 given weekly Route of Administration: Intramuscular (IM)
Other: Placebo
Treatment for hepatocellular carcinoma

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: Approximately 18 months
Time from study enrollment to death
Approximately 18 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression free survival
Time Frame: Approximately 18 months
Time from study enrollment to progressive disease or death
Approximately 18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Polaris Group

Investigators

  • Study Director: John S Bomalaski, Polaris Group

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 14, 2022

Primary Completion (Estimated)

September 1, 2025

Study Completion (Estimated)

October 1, 2025

Study Registration Dates

First Submitted

April 1, 2022

First Submitted That Met QC Criteria

April 1, 2022

First Posted (Actual)

April 8, 2022

Study Record Updates

Last Update Posted (Actual)

July 28, 2023

Last Update Submitted That Met QC Criteria

July 26, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • POLARIS2021-001

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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