intermediate stage hepatocellular carcinoma MedDRA version: 21.0 Level: LLT Classification code 10019828 Term: Hepatocellular carcinoma non-resectable System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Zavedos®
Product Name: idarubicin hydrochloride
Pharmaceutical Form: Powder for solution for injection
Sponsors
Department of Pharmaceutical Biosciences, Uppsala University
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female adults (=18 years), 2. Diagnosis of HCC: based on the Guidelines issued by AASLD (American Association for the Study of Liver Diseases) 3. HCC for which transplantation, surgical resection or percutaneous ablation are not indicated. 4. Child-Pugh = 7 p 5. Performance status: ECOG 0-2 (WHO), 6. Life expectancy of at least 3 months in absence of treatments 7. Has been vaccinated against Covid-19 or has a negative PCR-test. 8. Signature of informed consent obtained from the patient. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. Portal vein thrombosis, with the exception of thrombosis of a segment branch of the portal vein, 2. Extra hepatic cancer involvement, 3. Contraindications to arteriography, 4. Use of IDA and/or other anthracyclines for the last three months prior to inclusion into the study, 5. Previous or ongoing transarterial chemoembolization (TACE) treatment, 6. Known or suspect hypersensitivity to the investigational drug or to the investigational pharmacological class, 7. Presence of localized or systemic infections (with the exception of HIV infection responsive to therapy, HBV and HCV), 8. The patients must not be pregnant or attempt to get pregnant during the course of the study. Female patients of reproductive age must submit to a pregnancy test once monthly during the study and protect themselves from getting pregnant using a birth control method that can achieve a failure rate of less than 1% per year when used consistently and correctly (“Recommendations related to contraception and pregnancy testing in clinical trials”, supplied from www.hma.eu/ 9. 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. 10. Patients evaluated for a liver transplantation.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Study part A: To evaluate and compare the plasma pharmacokinetics of idarubicin and its active metabolite idarubicinol after two different doses of idarubicin administered with TACE in patients with hepatocellular carcinoma. Study part B: To evaluate long-term safety and population pharmacokinetics of idarubicin and idarubicinol in hepatocellular carcinoma patients treated with TACE.;Secondary Objective: •To evaluate tumour-uptake and lymphatic uptake of lipiodol with computer tomography (CT). •To evaluate the anti-tumour effect defined as changes in tumour volume, the amount of necrosis using positron emission tomography (PET) and magnetic resonance imaging (MRI), histopathology, liver biopsies from tumour and nontumor tissues, and multi-omics techniques. •To compare the anti-tumour effect (amount of necrosis) achieved in vivo and in vitro in the same tumours. •To evaluate cardiotoxicity, hematologic, liver safety and other adverse events (with established biomarkers). •To evaluate and compare the plasma pharmacokinetics of IDA and IDAol between the different single local doses of IDA-emulsion and to assess interindividual variability (IIV) and inter-occasion variability (IOV) as well as covariate relationships and to characterize the relationship between the PK and the hematological, cardio and liver toxicity.;Primary end point(s): Study part A: •To compare the plasma AUC(0-t) for idarubicin and idarubicinol between the two doses of 10 or 15 mg idarubicin . Study part B •To compare the plasma C(t) for idarubicin and idarubicinol between the two doses of 10 or 15 mg idarubicin. ;Timepoint(s) of evaluation of this end point: 24 h from administration | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Study part A • To evaluate tumour-uptake of lipiodol with computer tomography (CT). • To evaluate the anti-tumour effect defined as changes in tumour volume (evaluated with RECIST), and the amount of necrosis using positron emission tomography (PET) and magnetic resonance imaging (MRI). • To evaluate the effect of the IDA-lipiodol-emulsion on the regulation of the lipidome and proteome (metabolomics) of HCC and non-tumour cells with multi-omics analytical techniques in liver biopsies from tumour and nontumor tissues as well as liquid biopsies from blood/serum/plasma. • To explore changes in RNA-isolation, protein extraction and metabolomics/lipidomics assays in primary tumour material grown from liver biopsies cultured in 3D hydrogels in comparison with baseline. • To detect lipiodol in lymph ducts during TACE. • To evaluate cardiotoxicity, hematologic and liver safety, and other adverse events. Study part B • Pharmacokinetics (PK) endpoints: • Differences in plasma population C(t) clearance for IDA and IDAol between the two doses of 10 or 15 mg. • Imaging endpoints: • To quantify and localize Lipiodol deposition in the liver, reflecting the uptake of IDA, on CT after all TACE-treatments. • To assess tumour volume with RECIST1, and viability before and after all TACE-treatments on CT. • To investigate whether any differences between HCCs within and between patients identified in study part Aon pre-TACE MRIare correlated to overall treatment response (evaluated with RECIST), PFS, OS,and the occurrence and severity of adverse events • To detect lipiodol in lymph vessels at fluoroscopy during TACE. Biochemistry and cell biology endpoints: • To compare the plasma concentrations of a-fetoprotein before and after every TACE. • To detect circulating tumour cells in systemic blood circulation. • To compare the anti-tumour effect (amount of necrosis) achieved in vivo and in vitro in the same tumours and whether there is a correlation to any dif | — |
Countries
Sweden
Contacts
Public ContactProfessor
Department of Pharmaceutical Biosciences, Uppsala University
Outcome results
None listed