- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02089763
Efficacy Study of Pegylated Recombinant Human Arginase 1 as a Second-line Therapy in Patients With Advanced Liver Cancer
A Phase II Trial of PEG-BCT-100 as the Second-line Therapy Following Sorafenib in Patients With Advanced Hepatocellular Carcinoma
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This is a phase II, single-arm clinical trial. Approximately 35 subjects will be enrolled in the study. All subjects will be treated with PEG-BCT-100 2.7 mg/kg weekly (day1, 8 and 15). Three week treatment of PEG-BCT-100 is considered as 1 cycle. All subjects will receive PEG-BCT-100 till progressive disease, intolerable toxicity or patients withdraw consent.
The clinical effects of PEG-BCT-100 on disease response will be evaluated every 6 weeks until disease progression. Disease response evaluation will be based on RECIST 1.1 criteria. The disease response based on modified RECIST criteria will also be evaluated and documented for reference only.
Safety parameters will be evaluated throughout the study. Adverse event (AE) will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCI CTC AE v4).
All subjects will undergo a tumor tissue biopsy at baseline for evaluation of the biomarkers of ornithine transcarbamylase (OTC) and arginine succinate synthetase (ASS) except for those subjects whose tumor tissue blocks have been obtained within 1 year and are available for the biomarkers evaluation. The association between the levels of the 2 biomarkers and disease response to PEG-BCT-100 treatment will be explored in the study.
The effects on patients' quality of life will be evaluated every 2 cycles of the PEG-BCT-100 treatment.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
-
Hong Kong, Hong Kong
- Prince of Wales Hospital, The Chinese University of Hong Kong
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: PEG-BCT-100
pegylated recombinant human arginase 1
|
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to progression (TTP)
Time Frame: 3 years
|
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 lacking an evaluation of tumor response after their first dose will have their event time censored at Day 1. |
3 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression-free Survival (PFS)
Time Frame: 3 years
|
PFS is defined as the time from start of study treatment (Cycle 1 Day 1) to first documentation of objective tumor progression or to death due to any cause. PFS 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 lacking an evaluation of tumor response after their first dose will have their event time censored at Day 1. |
3 years
|
Overall Survival (OS)
Time Frame: 3 years
|
OS is defined as the time from start of study treatment to date of death due to any cause.
In the absence of confirmation of death, survival time will be censored at the last date the patient is known to be alive.
Patients lacking data beyond the day of first dose will have their survival times censored at 1 day.
|
3 years
|
Overall Response Rate (ORR)
Time Frame: 3 years
|
ORR is defined as the proportion of patients with confirmed complete response (CR) or confirmed partial response (PR), relative to the total evaluable patient population.
|
3 years
|
Disease Control Rate (DCR)
Time Frame: 3 years
|
DCR is defined as the percent of patients with confirmed CR, PR, or stable disease for at least 12 weeks on study, relative to the total evaluable patient population.
|
3 years
|
Duration of Response (DR)
Time Frame: 3 years
|
DR is defined as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause. DR data will be censored on the day following the date of the last tumor assessment documenting absence of progressive disease under the following conditions:
DR will only be calculated for the subgroup of patients with a tumor response (PR or CR). |
3 years
|
Quality of Life (QoL)
Time Frame: 3 years
|
The quality of life will be assessed at within 5 days prior to the start of trial treatment, every 2 cycles and at the End of Treatment.
Subjects are required to complete the questionnaires: EORTC QLQ-C30 and EORTC QLQ-HCC18
|
3 years
|
Safety profile of PEG-BCT-100 treatment
Time Frame: 3 years
|
Safety parameters will be evaluated throughout the study.
Adverse event (AE) will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCI CTC AE v4).
|
3 years
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Biomarker study - to explore the predictive and prognostic functions of tissue biomarkers, ornithine transcarbamylase (OTC) and arginine succinate synthetase (ASS)
Time Frame: 1 year
|
The tumor tissue biomarkers, OTC and ASS, will be measured at baseline using standard immunohistochemical (IHC) staining method.
IHC score will be produced for each tumor by summing up the intensity of the stain (0, 1, 2, 3) and the percentage of tumor with the corresponding intensity semi-quantitatively.
|
1 year
|
Collaborators and Investigators
Investigators
- Principal Investigator: Stephen L Chan, Dr., Chinese University of Hong Kong
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- BCT-100-006
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.
Clinical Trials on Hepatocellular Carcinoma
-
Academic and Community Cancer Research UnitedNational Cancer Institute (NCI)RecruitingUnresectable Hepatocellular Carcinoma | Stage III Hepatocellular Carcinoma AJCC v8 | Stage IIIA Hepatocellular Carcinoma AJCC v8 | Stage IV Hepatocellular Carcinoma AJCC v8 | Stage IVA Hepatocellular Carcinoma AJCC v8 | Stage IVB Hepatocellular Carcinoma AJCC v8 | BCLC Stage B Hepatocellular Carcinoma and other conditionsUnited States
-
Roswell Park Cancer InstituteMerck Sharp & Dohme LLCActive, not recruitingAdvanced Adult Hepatocellular Carcinoma | Child-Pugh Class A | Stage III Hepatocellular Carcinoma | Stage IIIA Hepatocellular Carcinoma | Stage IIIB Hepatocellular Carcinoma | Stage IIIC Hepatocellular Carcinoma | Stage IV Hepatocellular Carcinoma | Stage IVA Hepatocellular Carcinoma | Stage IVB Hepatocellular...United States
-
Roswell Park Cancer InstituteNational Comprehensive Cancer NetworkCompletedAdvanced Adult Hepatocellular Carcinoma | Localized Non-Resectable Adult Hepatocellular Carcinoma | Stage IIIA Hepatocellular Carcinoma | Stage IIIB Hepatocellular Carcinoma | Stage IIIC Hepatocellular Carcinoma | Stage IVA Hepatocellular Carcinoma | Stage IVB Hepatocellular Carcinoma | Stage III... and other conditionsUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)CompletedUnresectable Hepatocellular Carcinoma | Advanced Adult Hepatocellular Carcinoma | Stage IIIB Hepatocellular Carcinoma AJCC v7 | Stage IIIC Hepatocellular Carcinoma AJCC v7 | BCLC Stage C Hepatocellular Carcinoma | Stage IV Hepatocellular Carcinoma AJCC v7 | Stage III Hepatocellular Carcinoma AJCC... and other conditionsUnited States
-
Academic and Community Cancer Research UnitedNational Cancer Institute (NCI); Genentech, Inc.RecruitingUnresectable Hepatocellular Carcinoma | Stage III Hepatocellular Carcinoma AJCC v8 | Stage IIIA Hepatocellular Carcinoma AJCC v8 | Stage IV Hepatocellular Carcinoma AJCC v8 | Stage IVA Hepatocellular Carcinoma AJCC v8 | Stage IVB Hepatocellular Carcinoma AJCC v8 | Stage IIIB Hepatocellular Carcinoma... and other conditionsUnited States
-
National Cancer Institute (NCI)CompletedUnresectable Hepatocellular Carcinoma | Advanced Adult Hepatocellular Carcinoma | Recurrent Hepatocellular Carcinoma | Stage IIIB Hepatocellular Carcinoma AJCC v7 | Stage IIIC Hepatocellular Carcinoma AJCC v7 | Stage IV Hepatocellular Carcinoma AJCC v7 | Stage III Hepatocellular Carcinoma AJCC v7 and other conditionsUnited States, Canada, Puerto Rico
-
City of Hope Medical CenterNational Cancer Institute (NCI)RecruitingUnresectable Hepatocellular Carcinoma | Stage III Hepatocellular Carcinoma AJCC v8 | Stage IIIA Hepatocellular Carcinoma AJCC v8 | Stage IV Hepatocellular Carcinoma AJCC v8 | Stage IVA Hepatocellular Carcinoma AJCC v8 | Stage IVB Hepatocellular Carcinoma AJCC v8 | BCLC Stage B Hepatocellular Carcinoma and other conditionsUnited States
-
Mayo ClinicNational Cancer Institute (NCI)RecruitingAdvanced Hepatocellular Carcinoma | BCLC Stage B Hepatocellular Carcinoma | BCLC Stage C Hepatocellular Carcinoma | Metastatic Hepatocellular Carcinoma | BCLC Stage A Hepatocellular CarcinomaUnited States
-
Northwestern UniversityBristol-Myers Squibb; National Cancer Institute (NCI)CompletedStage IIIA Hepatocellular Carcinoma | Stage IIIB Hepatocellular Carcinoma | Stage IIIC Hepatocellular Carcinoma | Stage IVA Hepatocellular Carcinoma | Stage IVB Hepatocellular CarcinomaUnited States
-
OHSU Knight Cancer InstituteOregon Health and Science University; American Society of Clinical Oncology; Radiological... and other collaboratorsWithdrawnHepatocellular Carcinoma | Stage III Hepatocellular Carcinoma AJCC v8 | Stage IIIA Hepatocellular Carcinoma AJCC v8 | Stage IVA Hepatocellular Carcinoma AJCC v8 | Stage IIIB Hepatocellular Carcinoma AJCC v8 | Stage IB Hepatocellular Carcinoma AJCC v8 | Stage II Hepatocellular Carcinoma AJCC v8 | Stage... and other conditionsUnited States
Clinical Trials on pegylated recombinant human arginase
-
Bio-Cancer Treatment International LimitedOncotherapeuticsCompletedMelanoma | Prostate AdenocarcinomaUnited States
-
Bio-Cancer Treatment International LimitedThe University of Hong Kong; Chinese University of Hong KongCompletedHepatocellular Carcinoma | NeoplasmHong Kong
-
Eisai Inc.Halozyme TherapeuticsTerminated
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)WithdrawnStage IV Pancreatic Cancer AJCC v8 | Metastatic Pancreatic AdenocarcinomaUnited States
-
Bio-Cancer Treatment International LimitedThe University of Hong KongTerminated
-
Jiangsu T-Mab Biopharma Co.,LtdUnknownChemotherapy-induced NeutropeniaChina
-
Aeglea BiotherapeuticsCompletedAcute Myeloid Leukemia | Myelodysplastic SyndromeUnited States, Canada
-
Bio-Cancer Treatment International LimitedThe University of Hong Kong; Chinese University of Hong KongCompletedHepatocellular Carcinoma | NeoplasmHong Kong
-
Shandong UniversityShandong Provincial Hospital; The First Affiliated Hospital of Dalian Medical...CompletedImmune ThrombocytopeniaChina
-
Halozyme TherapeuticsCompletedGastric Cancer | NSCLCUnited States