Pegylated Recombinant Human Arginase 1 in Combination With Oxaliplatin and Capecitabine for the Treatment of HCC (PACOX)
|ClinicalTrials.gov Identifier: NCT02089633|
Recruitment Status : Completed
First Posted : March 18, 2014
Last Update Posted : July 28, 2017
|Condition or disease||Intervention/treatment||Phase|
|Hepatocellular Carcinoma||Biological: PACOX||Phase 2|
This is a phase II open-label study. The first part of the study (Part 1) is a dose escalation study of a 21-day regimen of IV Oxaliplatin in combination with weekly IV PEG-BCT-100 2.7 mg/kg and oral Capecitabine 1000 mg/m2 twice per day for 14 days. There are 3 successive treatment cohorts in dose level of 85 mg/m2, 100 mg/m2 and 130 mg/m2 for Oxaliplatin. Subsequent treatment cohort is opened only after all patients in the previous cohort have completed the first 3 cycles of PACOX. The first patient entered the study is started at Cohort 1. At least three subjects will be treated at this cohort and observed for dose-limiting toxicity (DLT). If one of the three treated patients develops DLT at any dose level, three additional patients are to be entered at the same dose level. The dose of Oxaliplatin will be escalated if no DLT for the first three patients or one of the six treated patients develops a DLT. If two or more of the three/six patients at a given dose level experienced a DLT, dose escalation is stopped and the previous dose level is declared the MTD (recommended dose) of PACOX regimen for the second part of the study (Part 2). If the first three patients in Cohort 3 do not develop a DLT, an additional three patients will be enrolled in Cohort 3. If one or less than one patient in Cohort 3 has developed a DLT. the dose level is declared as the MTD.
Toxicity will be assessed through physical examination and vital signs findings, safety laboratory tests results, and graded by the NCI CTCAE (version 4.0).
Part 2: Patients receive the recommended dose of PACOX regimen as defined in Part 1. A 14-day screening period followed by a treatment period consisting of 3-week treatment cycles. Patients will be treated until disease progression or intolerable toxicity. The treatment period will end by a follow up visit at 30 days after the last dose of trial treatment. After the study treatment, patients will be follow-up every 8 weeks for survival status or until study termination.
Patients in both parts of the study will receive PACOX regimen until disease progression, intolerable toxicity, death or patients withdraw consent. The clinical effects of PACOX regimen on tumor response will be evaluated. Tumour assessment which is based on RECIST 1.1 criteria will be performed until disease progression.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||17 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Study of the Safety and Efficacy of Recombinant Human Arginase 1 (PEG-BCT-100) Combined With Capecitabine and Oxaliplatin in Patients With Locally Advanced or Metastatic Hepatocellular Carcinoma|
|Study Start Date :||April 2014|
|Actual Primary Completion Date :||September 2016|
|Actual Study Completion Date :||October 2016|
Pegylated human arginase (PA) in combination with Capecitabine (C) and Oxaliplatin (OX)
Pegylated recombinant human arginase 1 in combination with Oxaliplatin and Capecitabine
- The maximum tolerated dose (MTD) of Oxaliplatin (OX) in combination with PEG-BCT-100 (PA) and Capecitabine (C) in patients with locally advanced or metastatic hepatocellular carcinoma [ Time Frame: 1 year ]There are 3 successive treatment cohorts in dose level of 85, 100 and 130 mg/m2 for Oxaliplatin. Subsequent treatment cohort is opened only after all patients in the previous cohort have completed the first 3 cycles of PACOX. At least 3 subjects will be treated at each cohort and observed for dose-limiting toxicity (DLT). If 1 of the 3 treated patients develops DLT at any dose level, 3 additional patients are to be entered at the same dose level. The dose of Oxaliplatin will be escalated if no DLT for the first 3 patients or 1 of the 6 treated patients develops a DLT. If 2 or more of the 3/6 patients at a given dose level experienced a DLT, dose escalation is stopped and the previous dose level is declared the MTD for the second part of the study. If the first 3 patients in Cohort 3 do not develop a DLT, an additional 3 patients will be enrolled in Cohort 3. If 1 or less than 1 patient in Cohort 3 has developed a DLT. the dose level is declared as the MTD.
- Time To Progression (TTP) [ Time Frame: 2 years ]TTP will be measured from the date of first dose of the PACOX regimen until documentation of disease progression according to RECIST 1.1 Criteria. Death due to cause other than progression will be censored. Patient without an event will be censored at date last known progression-free.
- Progression free survival (PFS) [ Time Frame: 2 years ]PFS will be measured as the start of the PACOX regimen until documentation of disease progression according to RECIST 1.1 Criteria or death due to any cause. Patients without an event will be censored at date last known progression-free
- Overall Survival (OS) [ Time Frame: 2 years ]OS is defined as the time form the start of PACOX regimen until death due to any cause, censored at the last date known alive.
- Response Rate (RR) [ Time Frame: 2 years ]The overall disease response rate in accordance with RECIST 1.1 Criteria, which is defined as the percentage of patients who achieve either a complete response (CR) or partial response (PR) or stable disease (SD)
- Serum alpha-fetoprotein (AFP) level [ Time Frame: 2 years ]change in serum AFP level from baseline.
- To evaluate the difference in disease response based on RECIST 1.1 Criteria and modified RECIST Criteria [ Time Frame: 2 years ]
- Safety events [ Time Frame: 3 years ]Adverse Event (AE)/Serious AE evaluated by NCI CTCAE, version 4.0
- To evaluate the association between the biomarkers of ornithine transcarbamoylase (OTC) and argininosuccinate synthetase (ASS) in liver tissue and clinical response treated with PACOX regimen [ 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.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02089633
|The University of Hong Kong, Queen Mary Hospital|
|Hong Kong, Hong Kong|
|Principal Investigator:||Thomas CC Yau, Dr.||The University of Hong Kong|