E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Intermediate hepatocellular carcinoma |
|
E.1.1.1 | Medical condition in easily understood language |
intermediate primary liver cancer |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019828 |
E.1.2 | Term | Hepatocellular carcinoma non-resectable |
E.1.2 | System Organ Class | 100000004864 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the plasma pharmacokinetics of doxorubicin and its active metabolite doxorubicinol after a single dose of doxorubicin-loaded DC bead or doxorubicin-lipiodol emulsion
|
|
E.2.2 | Secondary objectives of the trial |
• To evaluate the anti-tumor effect defined as tumor size and amount of necrosis using magnetic resonance imaging (MRI) 4-6 weeks after a single dose of one these two formulations. • To evaluate safety (liver function and adverse events) of the two products after a single dose of one these two formulations. • To evaluate the urinary excretion of doxorubicin and doxorubicinol 24 hours after a single dose of one these two formulations. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Adult (> 18 years), 2. Diagnosis of HCC: based on the Guidelines issued by AASLD (American Association for the Study of Liver Diseases) (latest diagnostic radiological imaging performed within 1 month from enrolment), 3. HCC for which transplantation, surgical resection or percutaneous ablation are not indicated, 4. Child-Pugh class A or B, 5. Performance status: ECOG 0-2 (WHO), 6. Life expectancy of at least 3 months in absence of treatments, 7. The following laboratory parameters must be met: Creatinine ≤ 115 μmol/L, Bilirubin ≤ 20.5 μmol/L, Albumin >= 35 g/L, White blood cells >= 1.5 x 109/L, INR >= 1.7, 8. Signature of informed consent obtained from the patient |
|
E.4 | Principal exclusion criteria |
1. Infiltrative HCC, 2. Liver tumor is undefined, immeasurable or not assessable, 3. Portal vein thrombosis, with the exception of thrombosis of a segment branch of the portal vein, 4. Extra-hepatic cancer involvement, 5. Contraindications to arteriography, 6. Use of doxorubicin and other anthracyclines in the last three months prior to inclusion into the study, 7. Previous or ongoing transarterial chemoinfusion (TAI) and/or chemoembolization (TACE) treatment of the same liver tumor (i.e. same lobular or segmental target area), 8. Known or suspect hypersensitivity to the investigational drug or to the investigational pharmacological class, 9. Ascites grade 2 or 3, 10. Patients presenting with severe clinical conditions which in the opinion of the investigator contraindicate patient participation in the study, 11. Presence of localized or systemic infections (with the exception of HIV infection responsive to therapy, HBV and HCV), 12. Pregnant women (women of child-bearing potential will have a pregnancy test done) and breastfeeding women, 13. Patients who are not capable of complying with the procedures established by the protocol and of signing the informed consent. In case of incapacitated patients unable to release their informed consent to take part in the study, the consent must be released and signed also by the parents/guardian or by the legal representative. Incapacitated patients must as well sign the informed consent to the best of their ability. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Primary pharmacokinetic parameters: AUC, Cmax, tmax, t1/2 of doxorubicin and its active metabolite doxorubicinol in plasma from two sampling sites (vena cava and peripheral vein) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
PK parameters will be collected during 24 h after the performed treatment |
|
E.5.2 | Secondary end point(s) |
Secondary variables to be assessed: Secondary effect variables: Anti-tumor response of treated lesion Secondary safety variables: A complete physical examination in addition to adverse events caused by the study and abnormal, clinically relevant, laboratory parameters assessed by liver function tests and α-fetoprotein to assess biohumoral levels of the disease. Secondary pharmacokinetic variables: Fraction excreted of doxorubicin and doxorubicinol in urine |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary effect variables: at 4-6 weeks post treatment assessed with MRI according to modified Response Evaluation Criteria in Solid Tumors (mRECIST). Secondary safety variables: A complete physical examination will be performed at screening and at the end of the study (at 4-6 weeks, after MRI). Blood samples including aminotransferases, bilirubin, alkaline phosphatase, CRP, albumin, creatinine, urea, electrolytes, hemoglobin, leukocytes and thrombocytes will be taken at screening, and 24 hours and 5-7 days after treatment. Secondary pharmacokinetic variables: urine will be collected during the first 24 h after treatment. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |