Study of Anti-tumour Effects and Safety of Prolarix™ in Hepatocellular Carcinoma
Condition: Hepatocellular Carcinoma
MeSH terms: Carcinoma; Carcinoma, Hepatocellular
Intervention: Prolarix (tretazicar co-administered with caricotamide)
Intervention description: Prolarix (26.6 mg/m2 tretazicar co-administered with 200 mg/m2 caricotamide) administered intravenously every 21 days until disease progression
Intervention MeSH terms: Tretazicar
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: hepatocellular carcinoma; liver cancer; Prolarix; tretazicar; caricotamide; Phase 2; tumor; chemotherapy

Summary:

      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.
    

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.