Efficacy Study of Pegylated Recombinant Human Arginase 1 as a Second-line Therapy in Patients With Advanced Liver Cancer

NCT02089763 | Completed Phase 2

• 1 other identifier: BCT-100-006
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to evaluate the efficacy and safety of PEG-BCT-100 as the second-line therapy following sorafenib in advanced HCC patients. Another objective of the study is to explore whether the expression of OTC and ASS are predictive biomarkers for drug response and prognosis.

Conditions

Hepatocellular Carcinoma

Keywords

Hepatocellular carcinoma; HCC; Pegylated recombinant human arginase; PEG-BCT-100; ASS; OTC

Outcome Measures

Primary Outcomes (1)

• Time to progression (TTP)

  TTP is defined as the time from start of study treatment (Cycle 1 Day 1) to first documentation of objective tumor progression. TTP data will be censored on the day following the date of the last tumor assessment documenting absence of progressive disease under the following conditions: * Patients who die for causes other than progressive disease * Patients who do not have objective tumor progression and are still on study at the time of an analysis * Patients who are given antitumor treatment other than the study treatment * Patients who are removed from study follow-up prior to documentation of objective tumor progression. Patients lacking an evaluation of tumor response after their first dose will have their event time censored at Day 1.

  3 years

Secondary Outcomes (7)

• Progression-free Survival (PFS)

  3 years

• Overall Survival (OS)

  3 years

• Overall Response Rate (ORR)

  3 years

• Disease Control Rate (DCR)

  3 years

• Duration of Response (DR)

  3 years

Other Outcomes (1)

• Biomarker study - to explore the predictive and prognostic functions of tissue biomarkers, ornithine transcarbamylase (OTC) and arginine succinate synthetase (ASS)

  1 year

Study Arms (1)

PEG-BCT-100

EXPERIMENTAL

pegylated recombinant human arginase 1

Biological: pegylated recombinant human arginase

Interventions

pegylated recombinant human arginase BIOLOGICAL

Also known as: PEG-BCT-100

PEG-BCT-100

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinical diagnosis of hepatocellular carcinoma (HCC) according to the European Association for the Study of the Liver (EASL) criteria
• Patients with advanced HCC defined as unresectable disease which is not amenable OR refractory to local-regional therapy OR with extra-hepatic involvement
• Patients have received prior systemic treatment with sorafenib for at least 14 days (not necessarily consecutive), and resulted in either disease progression or intolerance with sorafenib treatment
• Sorafenib must be the last antineoplastic treatment before enrollment
• Patients who are suitable for percutaneous tissue biopsy
• ECOG Performance Status 0-2
• Adequate hematological, renal and hepatic function as assessed by the following blood tests sampled at screening visit
• Life expectancy longer than 12 weeks
• Subjects with at least one measurable lesion assessed by CT scan or other imaging within 4 weeks prior to the first dose of PEG-BCT-100
• Normal ECG
• Patients who give written informed consent prior to any study specific screening procedures with the understanding that the patient has the right to withdraw from the study at any time, without prejudice.

You may not qualify if:

• Has received any surgery, loco-ablative, transarterial therapy or radiotherapy ≤ 2 weeks prior to the first dose of PEG-BCT-100
• Has received systemic cancer therapy, e.g. chemotherapy, targeted biologic or enzymes, either approved or investigational, ≤ 2 weeks prior to the first dose of PEG-BCT-100.
• Any toxic effects (except hair loss) of the prior therapy have not been resolved to Grade 2 or less according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events.
• Prior malignancy except cervical carcinoma in situ or treated basal cell carcinoma. Any cancers treated curatively \> 5 years prior to study entry are permitted.
• Child-Pugh class of B or C
• Patients with ascites uncontrolled by medication
• Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness.
• Prior treatment with arginine depleting agent.
• Female patients who are pregnant or lactating, or men and women of reproductive potential not willing or not able to employ an effective method of birth control/contraception to prevent pregnancy during treatment and for 6 months after discontinuing study treatment. The definition of effective contraception should be in agreement with local regulation and based on the judgment of the principal investigator or a designated associate.
• A serious uncontrolled medical disorder or active infection that would impair their ability to receive study treatment.
• Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol.
• Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study.
• Subjects, who in the opinion of the Investigator, are unable to comply with the trial treatment and the related trial procedures.

Sponsors & Collaborators

• Bio-Cancer Treatment International Limited: lead
• Chinese University of Hong Kong: collaborator
• The University of Hong Kong: collaborator

Study Sites (1)

Prince of Wales Hospital, the Chinese University of Hong Kong

Hong Kong, Hong Kong

Location

Related Publications (1)

• Chan SL, Cheng PNM, Liu AM, Chan LL, Li L, Chu CM, Chong CCN, Lau YM, Yeo W, Ng KKC, Yu SCH, Mok TSK, Chan AWH. A phase II clinical study on the efficacy and predictive biomarker of pegylated recombinant arginase on hepatocellular carcinoma. Invest New Drugs. 2021 Oct;39(5):1375-1382. doi: 10.1007/s10637-021-01111-8. Epub 2021 Apr 15.

  PMID: 33856599 RESULT

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

BCT-100

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Stephen L Chan, Dr.

  Chinese University of Hong Kong

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2014
• First Posted: March 18, 2014
• Study Start: April 1, 2014
• Primary Completion: March 1, 2017
• Study Completion: March 1, 2017
• Last Updated: August 9, 2021

Record last verified: 2021-08

Locations

HK (1)