Pegylated Recombinant Human Arginase 1 in Combination With Oxaliplatin and Capecitabine for the Treatment of HCC

NCT02089633 | Completed Phase 2 DMC

• 1 other identifier: BCT-100-004
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

The propose of the study is to evaluate the maximum tolerated dose (MTD) of Oxaliplatin in combination with pegylated recombinant human arginase 1 (PEG-BCT-100) and Capecitabine and efficacy of this combination regimen (PACOX)in patients with advanced liver cancer.

Conditions

Hepatocellular Carcinoma

Keywords

hepatocellular carcinoma; HCC; pegylated recombinant human arginase; PEG-BCT-100; oxaliplatin; capecitabine

Outcome Measures

Primary Outcomes (2)

• 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

  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.

  1 year

• Time To Progression (TTP)

  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.

  2 years

Secondary Outcomes (6)

• Progression free survival (PFS)

  2 years

• Overall Survival (OS)

  2 years

• Response Rate (RR)

  2 years

• Serum alpha-fetoprotein (AFP) level

  2 years

• To evaluate the difference in disease response based on RECIST 1.1 Criteria and modified RECIST Criteria

  2 years

Other Outcomes (1)

• 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

  1 year

Study Arms (1)

PACOX

EXPERIMENTAL

Pegylated human arginase (PA) in combination with Capecitabine (C) and Oxaliplatin (OX)

Biological: PACOX

Interventions

PACOX BIOLOGICAL

Pegylated recombinant human arginase 1 in combination with Oxaliplatin and Capecitabine

Also known as: PEG-BCT-100, Xeloda, Eloxatin

PACOX

Eligibility Criteria

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

You may qualify if:

• Age\>=18 years
• Histologically or cytologically or clinically diagnosed advanced HCC not amenable or refractory or intolerance to surgery, or local-regional therapy, or targeted therapy.
• Confirmed diagnosis of HCC according to the European Association for the Study of the Liver (EASL) criteria.
• Child-Pugh class A or B
• ECOG Performance State of 0 or 1
• Expected life expectancy of ≥ 12 weeks
• Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening
• Normal ECG
• Subjects with at least one measurable target lesion at baseline in accordance with RECIST 1.1 Criteria.
• 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:

• Prior use of any systemic anti-cancer treatment for HCC other than targeted therapy, e.g. sorafenib. Systemic anti-cancer treatment for HCC includes chemotherapy, immunotherapy and hormonal therapy (except hormonal therapy for supportive care is permitted). Antiviral treatment is allowed, however interferon therapy must be stopped at least 4 weeks prior to the start of trial treatment
• Prior use of any approved or investigational targeted therapy for HCC, e.g. sorafenib, within two weeks prior to the start of trial treatment
• Use of any local ablative treatment or TACE within 6 weeks prior to the start of trial treatment, and must have clear evidence of progressive disease after local treatment;
• Radiotherapy within 3 weeks prior to the start of trial treatment. (Palliative radiotherapy will be allowed)
• Major surgery within 4 weeks prior to the start of trial treatment
• Use of biologic response modifiers, such as G-CSF, within 3 week prior to the start of trial treatment.
• Concomitant treatment of rifampin or St John's Wort
• Other investigational products within 4 weeks prior to the start of the trial treatment
• Symptomatic metastatic brain or meningeal tumors (unless the patient is \> 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry).
• Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors \[Ta, Tis \& T1\] or any cancer curatively treated \> 3 years prior to study entry.
• Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within five days prior to the start of trial treatment. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial.
• History of cardiac disease: congestive heart failure \> NYHA class 2; active coronary artery disease (myocardial infarction more than 6 months prior to study entry is allowed); cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension
• History of HIV infection
• Known case of dihydropyrimidine dehydrogenase deficiency
• Active clinically serious infections (\> grade 2 NCI CTCAE version 4.0)

Sponsors & Collaborators

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

Study Sites (1)

The University of Hong Kong, Queen Mary Hospital

Hong Kong, Hong Kong

Location

Related Links

• Clinical Trails Centre, The University of Hong Kong

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

BCT-100; Capecitabine; Oxaliplatin

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

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Organic Chemicals

Study Officials

• Thomas CC Yau, Dr.

  The 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: September 1, 2016
• Study Completion: October 1, 2016
• Last Updated: July 28, 2017

Record last verified: 2017-07

Locations

HK (1)