Hepatocellular Carcinoma (HCC) MedDRA version: 9.1 Level: LLT Classification code 10019828 Term: Hepatocellular carcinoma non-resectable
Conditions
Interventions
Trade Name: Prolarix
Product Name: Prolarix
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Tretazicar
CAS Number: 21919-05
Current Sponsor code: Tretazicar
Concentrati
Sponsors
Protherics Development Medicines Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects must meet all of the following criteria to be eligible for enrolment into the study: 1) Subject must be =18 years of age. 2) 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). [Note: Subjects who have not yet had a tissue diagnosis may enter the Screening phase of the study if a) their clinical presentation is considered highly suggestive of HCC by the principal investigator and b) a tissue diagnosis is considered necessary for their management (subjects whom a tissue diagnosis is not considered essential for their management should not be enrolled on this study). A tissue diagnosis must be obtained prior to the entry of any subject into the treatment phase of the study. Subjects whom the principal investigator deems core biopsy to be indicated (as opposed to fine needle aspiration), will be requested to provide informed consent for a second pass biopsy (ie, in addition to the first pass biopsy for tissue diagnosis) for quantification of enzyme DT- diaphorase (NQO2) activity. The second pass biopsy is optional and subjects refusing a second pass biopsy may be enrolled in the study and will be treated identically to those accepting the second pass biopsy]. 3) Subject must have a measurable lesion by Response Evaluation Criteria in Solid Tumors (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). 4) Subject has an Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1. 5) 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]. 6) Subject has a minimum life expectancy of at least three months as determined by the investigator. 7) Subject has adequate bone marrow function (ie, haemoglobin =9 g/dL, granulocytes =1500/mm3, platelets =75,000/mm3). 8) Prothrombin time (PT)-international normalised ratio (INR) =2.3 or PT = equal to 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). 9) Subject has adequate renal function (ie, serum creatinine clearance is normal or calculated creatinine clearance is =60 mL/min). 10) Subject has adequate hepatic function (ie, bilirubin =2x upper limit of normal (ULN); aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase =5xULN). (Also see exclusion for Child-Pugh class C below). 11) 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. 12) Subject is able to give informed conse
Exclusion criteria
Exclusion criteria: Subjects meeting any of the following exclusion criteria will not be eligible for enrolment: 1) 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.) 2) 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). 3) Subject has Child-Pugh Class C hepatic impairment. 4) Subject has received an investigational drug within 30 days of enrolment in the study. 5) Females of childbearing potential unless using adequate contraception. 6) Pregnant or lactating females. 7) Major variceal bleeding in the last 30 days. 8) Subjects with a known history of human immunodeficiency virus (HIV) infection
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the overall response rate [ie, proportion of subjects with complete response (CR) and partial response (PR)] to treatment with Prolarix at the MTD determined in a previous Phase 1 study (26.6 mg/m2 tretazicar co-administered with 200 mg/m2 caricotamide).;Secondary Objective: Secondary Objectives: To evaluate the disease control rate defined as the proportion of subjects with either CR or PR or stable disease (SD) at tumour assessment performed approximately 12 weeks or more after first treatment with Prolarix. To evaluate time to tumour progression (TTP). To evaluate indications of anti-tumour activity as supported by post-treatment changes in the amount of contrast-enhancing and non-contrast-enhancing tumour and by changes in alpha fetoprotein. To evaluate the toxicity profile of Prolarix in subjects with HCC. To evaluate the pharmacokinetic profiles of tretazicar and caricotamide in subjects with HCC. ;Primary end point(s): Overall tumour response will be based on the best tumour response in all subjects. Tumour responses for targeted and non-targeted tumours are defined using modified RECIST criteria with the modification that confirmatory CT is not required to define tumour response Evaluation of target lesions 1) Complete Response (CR): Disappearance of all target lesions 2) Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. 3) Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. 4) Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions Evaluation of non-target lesions 1) Complete Response (CR): Disappearance of all non-target lesions and | — |
Countries
Belgium, United Kingdom
Outcome results
None listed