Hepatocellular CarcinomaPhase 2PACOXNCT02089633
Pegylated Recombinant Human Arginase 1 in Combination With Oxaliplatin and Capecitabine for the Treatment of HCC
A Phase 2 study testing PACOX in people with Hepatocellular Carcinoma, run by Bio-Cancer Treatment International Limited at 1 site in Hong Kong.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- PACOX
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteHong Kong
- Study dates
- Apr 2014to Oct 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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.
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- 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)
- Patients with clinically significant gastrointestinal bleeding within 30 days prior to the start of trial treatment.
- Patients with main portal vein tumor thrombosis
- Patients with ascites uncontrolled by medication
- Patients with seizure disorder requiring medication (such as steroids or anti-epileptics)
- Patients with previous liver transplantation
- Patients undergoing renal dialysis
- Known or suspected hypersensitivity to capecitabine, 5-fluorouracil, oxaliplatin or other platinum compounds, and any other agent given in association with this trial
- Patients with significant peripheral sensory neuropathy with functional impairment
- patients unable to swallow oral medications
- Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the detailed description
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.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- PACOX
- Keywords
- hepatocellular carcinoma, HCC, pegylated recombinant human arginase, PEG-BCT-100, oxaliplatin, capecitabine
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PACOXBiological
Also called PEG-BCT-100, Xeloda, Eloxatin
Pegylated recombinant human arginase 1 in combination with Oxaliplatin and Capecitabine
| Study group | Role | What they receive |
|---|---|---|
| PACOX | Experimental | Pegylated human arginase (PA) in combination with Capecitabine (C) and Oxaliplatin (OX) Receives: Biological: PACOX |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 2 years
Secondary outcomes (6)
Progression free survival (PFS)
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
Measured: 2 years
Overall Survival (OS)
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.
Measured: 2 years
Response Rate (RR)
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)
Measured: 2 years
Serum alpha-fetoprotein (AFP) level
change in serum AFP level from baseline.
Measured: 2 years
To evaluate the difference in disease response based on RECIST 1.1 Criteria and modified RECIST Criteria
Measured: 2 years
Safety events
Adverse Event (AE)/Serious AE evaluated by NCI CTCAE, version 4.0
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2014 (estimated)
- Study startApr 2014
- Primary completionSep 2016
- Study completionOct 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bio-Cancer Treatment International Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- The University of Hong Kong
- Responsible party
- Sponsor
- Investigators
- Thomas CC Yau, Dr., Principal investigator, The University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02089633
- Sponsor's protocol ID
- BCT-100-004
- Acronym
- PACOX
- Status last verified
- Jul 2017
- First submitted
- 14 Mar 2014
- Last updated
- 28 Jul 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02089633
- Acronym / sponsor ID
- PACOX / BCT-100-004
- Conditions
- Hepatocellular Carcinoma
- Keywords
- hepatocellular carcinoma, HCC, pegylated recombinant human arginase, PEG-BCT-100, oxaliplatin, capecitabine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Bio-Cancer Treatment International LimitedIndustry (pharma, biotech, devices)
- Collaborators
- The University of Hong Kong
- Study start
- Apr 2014
- Primary completion
- Sep 2016 (actual)
- Study completion
- Oct 2016 (actual)
- First posted
- 18 Mar 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PACOX | Experimental | Biological: PACOXPegylated human arginase (PA) in combination with Capecitabine (C) and Oxaliplatin (OX) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (25 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PACOXAlso: PEG-BCT-100, Xeloda, EloxatinPegylated recombinant human arginase 1 in combination with Oxaliplatin and Capecitabine | Biological | PACOX |
Primary outcome
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.
6 secondary outcomes
Progression free survival (PFS)
Time frame: 2 years
Overall Survival (OS)
Time frame: 2 years
Response Rate (RR)
Time frame: 2 years
Serum alpha-fetoprotein (AFP) level
Time frame: 2 years
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2017.
- Clinical Trails Centre, The University of Hong KongLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Thomas CC Yau, Dr. principal investigator
The University of Hong Kong
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing PACOX in people with Hepatocellular Carcinoma, run by Bio-Cancer Treatment International Limited at 1 site in Hong Kong.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Hong Kong. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2017.