Study of Anti-tumour Effects and Safety of Prolarix™ in Hepatocellular Carcinoma

This an open-label study designed to evaluate the anti-tumour activity and safety of Prolarix in subjects with advanced hepatocellular carcinoma.

Prolarix is a chemotherapy comprised of tretazicar as prodrug and caricotamide as co-substrate for the endogenous enzyme, NQO2.

The primary objective of this study is to evaluate the anti-tumour effects of treatment with Prolarix in subjects with advanced HCC (Child-Pugh A and B only).

All subjects will receive an IV infusion of Prolarix once every 21 days until disease progression is observed.

Subjects will have CT scans for tumour measurements before starting treatment with Prolarix and every 6 weeks until disease progression.

Subjects will undergo evaluation for safety (adverse events, vital signs, clinical laboratory measurements, weight, ECG) every 21 days until disease progression.

Eligibility Criteria:
Inclusion Criteria:

* Subject must be at least 18 years of age.
* Subject must have a histologic or cytologic diagnosis of HCC and be considered unsuitable for resection or other potentially curative options (eg, liver transplant, curative radiofrequency ablation).
* Subject must have a measurable lesion by RECIST on CT scan in at least one site which has not received radiation or any other local therapy \[eg, transcatheter arterial chemoembolisation (TACE), radiofrequency ablation, local injection\]. (Note: Subjects who have received local therapies will be allowed to participate, provided that they have a target lesion which has not been subjected to local therapy. Subjects who have received TACE must have a target lesion outside of the vascular territory subjected to chemoembolisation.)
* Subject has an Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1.
* Subject has had no other active malignancy within the past three years \[other than non melanomatous skin cancer or carcinoma in situ (CIS) of the breast, bladder, or uterine cervix. Subjects with Ta (non-invasive papillary carcinoma) or Tis (sessile carcinoma in situ) bladder cancer are allowed\].
* Subject has a minimum life expectancy of at least three months as determined by the investigator.
* Subject has adequate bone marrow function (ie, haemoglobin ≥9 g/dL, granulocytes ≥1500/mm3, platelets ≥75,000/mm3).
* Prothrombin time (PT)-international normalised ratio (INR) ≤2.3 or PT ≤6 seconds above control. (Note: Subjects who are being therapeutically anticoagulated with an agent such as warfarin or heparin will be allowed to participate provided that their INR is between 2.0 and 3.0.
* Subject has adequate renal function (ie, serum creatinine is normal or calculated creatinine clearance is ≥60 mL/min).
* Subject has adequate hepatic function (ie, bilirubin ≤2x upper limit of normal (ULN); AST ALT, and alkaline phosphatase ≤5xULN). (Also see exclusion for Child-Pugh class C below).
* Male subjects and females of childbearing potential must agree to use an adequate method of contraception from the time of initiation of treatment through study participation and for 3 months after release from the study.
* Subject is able to give informed consent.

Exclusion Criteria:

* Any prior or current systemic pharmacotherapy for HCC (cytotoxic, targeted or biologic). (Note: TACE is not considered to be systemic pharmacotherapy for the purpose of this study).
* Subject has an absolute contraindication to receiving CT contrast media. (Note: Subjects with a history of minor contrast reactions may be pre-medicated prior to contrast administration in accordance with local or institutional practice).
* Subject has Child-Pugh Class C hepatic impairment.
* Subject has received an investigational drug within 30 days of enrolment in the study.
* Females of childbearing potential unless using adequate contraception.
* Pregnant or lactating females.
* Major variceal bleeding in the last 30 days.
* Subjects with a known history of human immunodeficiency virus (HIV) infection.