E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
post-resection hepatocellular carcinoma Carcinoma hepatocelular post-resección |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019830 |
E.1.2 | Term | Hepatocellular carcinoma resectable |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to compare the disease-free survival (DFS) for subjects treated with PI-88 versus placebo. |
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E.2.2 | Secondary objectives of the trial |
• Overall survival for subjects treated with PI-88 versus placebo • Time to recurrence for subjects treated with PI-88 versus placebo • Safety and tolerability of PI-88 • Impact on quality of life of PI-88 when compared to placebo • Compliance of subjects with self-administration of PI-88 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histologically-proven hepatocellular carcinoma with curative resection performed within 4-6 weeks prior to randomisation and confirmed by negative follow-up chest and abdominal CT scans and abdominal MRI scan 2. Age ≥18 years 3. Written, signed and dated informed consent to participate in study 4. Able and willing to meet all protocol-required treatments, investigations and visits. This must include the ability for the subject to comply with daily self-administration of a subcutaneous injection, or reliable means for injections to be administered by a dependable third party such as a relative or caregiver. 5. ECOG performance status 0 to 2 6. Child Pugh classification A or B 7. ALT & AST within 2.5 times upper limit of normal (ULN) 8. Total bilirubin within 1.5 times upper limit of normal (ULN) 9. Platelet count ≥ 100 x 109 cells / litre 10. PT-INR less than 1.3 times upper limit of normal (ULN) 11. aPTT within normal range |
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E.4 | Principal exclusion criteria |
1. Any evidence of tumour metastasis or co-existing malignant disease 2. Any prior history of malignant disease, except:- (a) Non-invasive, non-melanomatous skin cancer (b) Treated in-situ cancer of the cervix 3. Any prior recurrence of HCC or any liver resection prior to the most recent procedure 4. Clinically significant non-malignant disease. Subjects who have experienced post-operative complications of liver resection may be enrolled providing that such complications are fully resolved at the time of screening. 5. Significant laboratory abnormalities including, but not limited to:- (a) Total white blood cell (WBC) count < 2.3 x 109 / litre (<2,300 /mm3) (b) Total neutrophil count < 1.5 x 109 / litre (1,500 /mm3) (c) Serum creatinine > 1.5 times upper limit of normal (ULN) 6. History of prior HCC therapy including, but not limited to, radiofrequency ablation, chemoembolization, chemotherapy, radiotherapy, molecular targeting agents, vaccines, liver transplantation or surgical resection prior to the most recent hepatectomy, at any time prior to screening 7. History of allergy and / or hypersensitivity and / or other clinically significant adverse drug reaction to heparin or other anti-coagulant agents 8. History of immune-mediated thrombocytopaenia or other platelet abnormalities or other hereditary or acquired coagulopathies, or laboratory evidence of anti-heparin antibodies, or any previous history of having tested positive to anti-heparin antibodies 9. Concomitant use of aspirin (>150mg / day), non-steroidal anti-inflammatory drugs (except COX-2 selective inhibitors), vitamin K antagonists (other than low-dose prophylactic use), heparin within two weeks prior to randomisation, or other anti-platelet drugs (e.g. abciximab, clopidogrel, dipyridamole, ticlopidine and tirofiban). Low-dose aspirin (≤150mg / day) and low-dose prophylactic vitamin K antagonists (e.g. warfarin ≤1mg / day) are permitted as concomitant medications. 10. History of allergic, anaphylactic or other significant adverse reaction to radiographic contrast media (iodinated or noniodinated). 11. Known seropositivity to the human immunodeficiency virus (HIV). 12. Women who are pregnant or breast-feeding, or women of child-bearing potential who are unable or unwilling to practice a highly effective means of contraception 13. Active substance abuse, including alcohol, which, in the opinion of the investigator, risks impairing the ability of the subject to comply with the protocol 14. Current participation in any other clinical study or research project which involves administration of a pharmaceutical product or experimental treatment, or which involves protocol-specified laboratory tests, imaging studies or other investigations |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy Parameters: • Disease-free survival (DFS) • Overall survival (OS) • Time to recurrence (TTR) • SF-36 quality of life instrument
Safety Parameters: • Physical examination, including vital signs • Adverse event monitoring • Blood chemistry, haematology, liver function, clotting function and urinalysis • Anti-heparin antibodies (in subjects who develop significant thrombocytopaenia) • Treatment compliance
Other Parameters: In a cohort of 40-50 subjects at 4-8 selected sites, additional pharmacokinetic and pharmacodynamic measurements will be conducted at two scheduled study visits. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 14 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |