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Study protocol for locoregional precision treatment of hepatocellular carcinoma with transarterial chemoembolisation (TACTida), a clinical study: idarubicin dose selection, tissue response and survival.
Nyman, Sofi Sennefelt; Ahlström, Håkan; Creusen, Angeliki Dimopoulou; Dahlgren, David; Hedeland, Mikael; Heindryckx, Femke; Johnson, Ulf; Khaled, Jaafar; Kullenberg, Fredrik; Nyman, Rickard; Rorsman, Fredrik; Sheikhi, Reza; Simonsson, Ulrika S H; Sjögren, Erik; Wanders, Alkwin; Lennernäs, Hans; Ebeling Barbier, Charlotte.
Afiliação
  • Nyman SS; Department of Surgical Sciences, Section of Radiology, Uppsala University, Uppsala, Sweden sofi_nyman@hotmail.com.
  • Ahlström H; Department of Surgical Sciences, Section of Radiology, Uppsala University, Uppsala, Sweden.
  • Creusen AD; Department of Surgical Sciences, Section of Radiology, Uppsala University, Uppsala, Sweden.
  • Dahlgren D; Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
  • Hedeland M; Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry, Uppsala University, Uppsala, Sweden.
  • Heindryckx F; Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
  • Johnson U; Department of Surgical Sciences, Section of Radiology, Uppsala University, Uppsala, Sweden.
  • Khaled J; Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
  • Kullenberg F; Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
  • Nyman R; Department of Surgical Sciences, Section of Radiology, Uppsala University, Uppsala, Sweden.
  • Rorsman F; Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
  • Sheikhi R; Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
  • Simonsson USH; Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
  • Sjögren E; Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
  • Wanders A; Department of Pathology, Aalborg University Hospital, Aalborg, Denmark.
  • Lennernäs H; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
  • Ebeling Barbier C; Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
BMJ Open ; 12(11): e065839, 2022 11 07.
Article em En | MEDLINE | ID: mdl-36343995
ABSTRACT

INTRODUCTION:

Hepatocellular carcinoma (HCC) is a common cause of cancer-related death, often detected in the intermediate stage. The standard of care for intermediate-stage HCC is transarterial chemoembolisation (TACE), where idarubicin (IDA) is a promising drug. Despite the fact that TACE has been used for several decades, treatment success is unpredictable. This clinical trial has been designed believing that further improvement might be achieved by increasing the understanding of interactions between local pharmacology, tumour targeting, HCC pathophysiology, metabolomics and molecular mechanisms of drug resistance. METHODS AND

ANALYSIS:

The study population of this single-centre clinical trial consists of adults with intermediate-stage HCC. Each tumour site will receive TACE with two different IDA doses, 10 and 15 mg, on separate occasions. Before and after each patient's first TACE blood samples, tissue and liquid biopsies, and positron emission tomography (PET)/MRI will be performed. Blood samples will be used for pharmacokinetics (PK) and liver function evaluation. Tissue biopsies will be used for histopathology analyses, and culturing of primary organoids of tumour and non-tumour tissue to measure cell viability, drug response, multiomics and gene expression. Multiomics analyses will also be performed on liquid biopsies. PET/MRI will be used to evaluate tumour viability and liver metabolism. The two doses of IDA will be compared regarding PK, antitumour effects and safety. Imaging, molecular biology and multiomics data will be used to identify HCC phenotypes and their relation to drug uptake and metabolism, treatment response and survival. ETHICS AND DISSEMINATION Participants give informed consent. Personal data are deidentified. A patient will be withdrawn from the study if considered medically necessary, or if it is the wish of the patient. The study has been approved by the Swedish Ethical Review Authority (Dnr. 2021-01928) and by the Medical Product Agency, Uppsala, Sweden. TRIAL REGISTRATION NUMBER EudraCT number 2021-001257-31.
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Texto completo: 1 Coleções: 01-internacional Temas: Geral / Tipos_de_cancer / Outros_tipos Base de dados: MEDLINE Assunto principal: Quimioembolização Terapêutica / Carcinoma Hepatocelular / Neoplasias Hepáticas Tipo de estudo: Guideline Limite: Humans Idioma: En Revista: BMJ Open Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Suécia

Texto completo: 1 Coleções: 01-internacional Temas: Geral / Tipos_de_cancer / Outros_tipos Base de dados: MEDLINE Assunto principal: Quimioembolização Terapêutica / Carcinoma Hepatocelular / Neoplasias Hepáticas Tipo de estudo: Guideline Limite: Humans Idioma: En Revista: BMJ Open Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Suécia