Clinical trial protocol for PanDox: a phase I study of targeted chemotherapy delivery to non-resectable primary pancreatic tumours using thermosensitive liposomal doxorubicin (ThermoDox®) and focused ultrasound.

Autor: Spiers L; Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK.; Oxford University Hospitals NHS Foundation Trust, Oxford, OX3 7LE, UK.; NIHR Oxford Biomedical Research Centre, Oxford, UK., Gray M; NIHR Oxford Biomedical Research Centre, Oxford, UK.; Institute of Biomedical Engineering, University of Oxford, Marcella Wing, Botnar Research Centre, Old Rd, Headington, Oxford, OX3 7LD, UK., Lyon P; Oxford University Hospitals NHS Foundation Trust, Oxford, OX3 7LE, UK., Sivakumar S; Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK.; Oxford University Hospitals NHS Foundation Trust, Oxford, OX3 7LE, UK., Bekkali N; Oxford University Hospitals NHS Foundation Trust, Oxford, OX3 7LE, UK., Scott S; Nuffield Department of Anaesthetics, John Radcliffe Hospital, Oxford, OX3 7LE, UK., Collins L; Department of Oncology, Oncology Clinical Trials Office (OCTO), University of Oxford, Oxford, UK., Carlisle R; Institute of Biomedical Engineering, University of Oxford, Marcella Wing, Botnar Research Centre, Old Rd, Headington, Oxford, OX3 7LD, UK., Wu F; Nuffield Department of Surgery, Churchill Hospital, Oxford, OX3 7LE, UK., Middleton M; Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK., Coussios C; Institute of Biomedical Engineering, University of Oxford, Marcella Wing, Botnar Research Centre, Old Rd, Headington, Oxford, OX3 7LD, UK. laura.spiers@ouh.nhs.uk.
Jazyk: angličtina
Zdroj: BMC cancer [BMC Cancer] 2023 Sep 23; Vol. 23 (1), pp. 896. Date of Electronic Publication: 2023 Sep 23.
DOI: 10.1186/s12885-023-11228-z
Abstrakt: Background: The dense stroma of pancreatic ductal adenocarcinomas is a major barrier to drug delivery. To increase the local drug diffusion gradient, high doses of chemotherapeutic agent doxorubicin can be released from thermally-sensitive liposomes (ThermoDox®) using ultrasound-mediated hyperthermia at the tumour target. PanDox is designed as a Phase 1 single centre study to investigate enhancing drug delivery to adult patients with non-operable pancreatic ductal adenocarcinomas. The study compares a single cycle of either conventional doxorubicin alone or ThermoDox® with focused ultrasound-induced hyperthermia for targeted drug release.
Methods: Adults with non-resectable pancreatic ductal adenocarcinoma are allocated to receive a single cycle of either doxorubicin alone (Arm A) or ThermoDox® with focused ultrasound-induced hyperthermia (Arm B), based on patient- and tumour-specific safety conditions. Participants in Arm B will undergo a general anaesthetic and pre-heating of the tumour by extra-corporal focused ultrasound (FUS). Rather than employing invasive thermometry, ultrasound parameters are derived from a patient-specific treatment planning model to reach the 41 °C target temperature for drug release. ThermoDox® is then concurrently infused with further ultrasound exposure. Tumour biopsies at the targeted site from all patients are analysed post-treatment using high performance liquid chromatography to quantify doxorubicin delivered to the tumour. The primary endpoint is defined as a statistically significant enhancement in concentration of total intra-tumoural doxorubicin, comparing samples from patients receiving liposomal drug with FUS to free drug alone. Participants are followed for 21 days post-treatment to assess secondary endpoints, including radiological assessment to measure changes in tumour activity by Positron Emission Tomography Response Criteria in Solid Tumours (PERCIST) criteria, adverse events and patient-reported symptoms.
Discussion: This early phase study builds on previous work targeting tumours in the liver to investigate whether enhancement of chemotherapy delivery using ultrasound-mediated hyperthermia can be translated to the stroma-dense environment of pancreatic ductal adenocarcinoma. If successful, it could herald a new approach towards managing these difficult-to-treat tumours.
Trial Registration: ClinicalTrials.gov Identifier: NCT04852367 . Registered 21 st April 2022. EudraCT number: 2019-003950-10 (Registered 2019) Iras Project ID: 272253 (Registered 2019) Ethics Number: 20/EE/0284.
(© 2023. BioMed Central Ltd., part of Springer Nature.)
Databáze: MEDLINE
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