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

This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring hepatocellular carcinoma, HCC, pegylated recombinant human arginase, PEG-BCT-100, oxaliplatin, capecitabine Read More

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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)
• 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