Clinical Trials List
Protocol NumberPOLARIS2013-003
NCT Number(ClinicalTrials.gov Identfier)NCT02006030
Completed
2014-04-20 - 2016-05-20
Phase II
Terminated3
Study ended1
ICD-10C22.9
Malignant neoplasm of liver, not specified as primary or secondary
Randomized, Open Label, Phase 2 Trial of ADI-PEG 20 plus Concurrent Transarterial Chemoembolization (TACE) Versus TACE Alone in Patients with Unresectable Hepatocellular Carcinoma
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Trial Applicant
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Sponsor
TDW Pharmaceuticals, Inc.
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Trial scale
Taiwan Multiple Center
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Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- Yi-Hsiang Huang Division of General Internal Medicine
- Gar-Yang Chau Division of General Surgery
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- 洪建福 Division of Radiology
- Chao-Wei Hsu Division of General Internal Medicine
- 周宏學 Division of General Surgery
- I-Shyan Sheen Division of General Internal Medicine
- 陳威廷 Division of General Internal Medicine
- 周宏學 Division of General Surgery
- Shi-Ming Lin Division of General Internal Medicine
- Wei-Chen Lee Division of General Surgery
- Chau-Ting Yeh Division of General Internal Medicine
- Ming-Chin Yu Division of General Surgery
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Cheng-Yuan Peng Division of General Internal Medicine
- Hsueh-Chou Lai Division of General Internal Medicine
- Po-Heng Chuang Division of General Internal Medicine
- 陳永芳 Division of Radiology
The Actual Total Number of Participants Enrolled
5 Study ended
Co-Principal Investigator
- - - Division of Radiology
- Ming-Chih Ho Division of General Surgery
- 蘇東弘 Division of General Internal Medicine
- Chun-Jen Liu Division of General Internal Medicine
- Chien-Hung Chen Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Condition/Disease
Unresectable Hepatocellular Carcinoma
Objectives
The primary objective of this study is: Determine time to tumor progression (TTP)
• The secondary objectives of this study are:Assessment of safety and tolerability, Tumor
response rates, Determine progression free survival (PFS), Determine objective responses, Determine disease control rate (DCR), Determine overall survival (OS), Determine the pharmacodynamics of ADI-PEG 20 in combination with TACE, Determine the immunogenicity of ADI-PEG 20 in combination with TACE
Test Drug
ADI-PEG 20
Active Ingredient
Arginine deiminase conjugated to polyethylene glycol 20,000 mw
Dosage Form
Injection
Dosage
11.0±1.0
Endpoints
Performed by the sponsor and its representatives
Safety: Adverse events, laboratory tests, vital sign measurements, and physical examinations
Efficacy: Tumor response rates, time to tumor progression, progression free survival, overall survival, objective response and disease control rates
Safety: Adverse events, laboratory tests, vital sign measurements, and physical examinations
Efficacy: Tumor response rates, time to tumor progression, progression free survival, overall survival, objective response and disease control rates
Inclution Criteria
1. Prior diagnosis of HCC confirmed clinically or histologically or cytologically. A clinical diagnosis of HCC requires the following: (i) positive for hepatitis B or C and/or evidence of liver cirrhosis, (ii) presence of hepatic tumor(s) with image findings (sonography, CT or MRI) compatible with HCC, (iii) no evidence of other gastrointestinal tumors, and (iv) persistent elevation of serum alpha-fetoprotein (AFP) level ≥ 400 ng/ml without any evidence of an existing AFP-secreting germ cell tumor.
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, ryoablation, 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 6 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 RECIST (Appendix B) criteria. At least 1 measurable lesion must be present.
8. Barcelona Clinic Liver Cancer (BCLC) staging classification B (intermediate stage) (Appendix C). That is, multinodular asymptomatic tumors, without extra-hepatic spread (second branch invasion of the unilateral lobe is not allowed).
9. ECOG performance status of 0 – 1 (Appendix E).
10. 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 D). Subjects on anti-coagulants are to receive only 1 point for their INR status.
11. Expected survival of at least 3 months.
12. Age ≥ 18 years.
13. Fully recovered from prior major surgery and none within 2 weeks prior to week 1 visit. Liver biopsy for HCC confirmation is allowed.
14. 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.
15. Informed consent must be obtained prior to study initiation.
16. No concurrent investigational studies are allowed.
17. Total bilirubin < 2.5 mg/dL and no evidence of bile obstruction.
18. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤5 x upper limit of normal range.
19. Absolute neutrophil count (ANC) >1,500/µL.
20. Platelets >50,000/µL.
21. Serum uric acid ≤ 8 mg/dL (with or without medication control).
22. 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 ≥ 60 mL/min.
23. Serum albumin level ≥ 3.0 g/dl.
24. Prothrombin time (PT)-international normalized ratio (INR): PT <3 seconds above control or INR <1.7.
25. Subjects with active hepatitis B or C on anti-viremic compounds may remain on such treatment, except for interferon.
26. Encephalopathy – none or mild (grade 1 or 2, by Child-Pugh classification); lactulose of other supportive care allowed.
27. Ascites – absent or slight (by Child-Pugh classification); diuretic therapy allowed
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, ryoablation, 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 6 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 RECIST (Appendix B) criteria. At least 1 measurable lesion must be present.
8. Barcelona Clinic Liver Cancer (BCLC) staging classification B (intermediate stage) (Appendix C). That is, multinodular asymptomatic tumors, without extra-hepatic spread (second branch invasion of the unilateral lobe is not allowed).
9. ECOG performance status of 0 – 1 (Appendix E).
10. 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 D). Subjects on anti-coagulants are to receive only 1 point for their INR status.
11. Expected survival of at least 3 months.
12. Age ≥ 18 years.
13. Fully recovered from prior major surgery and none within 2 weeks prior to week 1 visit. Liver biopsy for HCC confirmation is allowed.
14. 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.
15. Informed consent must be obtained prior to study initiation.
16. No concurrent investigational studies are allowed.
17. Total bilirubin < 2.5 mg/dL and no evidence of bile obstruction.
18. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤5 x upper limit of normal range.
19. Absolute neutrophil count (ANC) >1,500/µL.
20. Platelets >50,000/µL.
21. Serum uric acid ≤ 8 mg/dL (with or without medication control).
22. 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 ≥ 60 mL/min.
23. Serum albumin level ≥ 3.0 g/dl.
24. Prothrombin time (PT)-international normalized ratio (INR): PT <3 seconds above control or INR <1.7.
25. Subjects with active hepatitis B or C on anti-viremic compounds may remain on such treatment, except for interferon.
26. Encephalopathy – none or mild (grade 1 or 2, by Child-Pugh classification); lactulose of other supportive care allowed.
27. Ascites – absent or slight (by Child-Pugh classification); diuretic therapy allowed
Exclusion Criteria
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.
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. HIV testing is not required.
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 (GCSF) within 7 days prior to screening laboratories or after screening laboratories have been obtained until week 1 visit.
18. Use of traditional medicines approved by local authorities, including but not limited to Chinese herbs within 2 weeks prior to week 1 visit.
19. Eastern Cooperative Oncology Group (ECOG) performance status ≥ 2.
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.
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. HIV testing is not required.
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 (GCSF) within 7 days prior to screening laboratories or after screening laboratories have been obtained until week 1 visit.
18. Use of traditional medicines approved by local authorities, including but not limited to Chinese herbs within 2 weeks prior to week 1 visit.
19. Eastern Cooperative Oncology Group (ECOG) performance status ≥ 2.
The Estimated Number of Participants
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Taiwan
30 participants
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Global
30 participants
