Celsion Announces Publication of ThermoDox® Study Results in Radiology
Publication Highlights Phase I Data Supporting Safety and Feasibility of Treatment with ThermoDox® and Non-Invasive, Focused Ultrasound
University of Oxford’s Findings Provide Additional Independent Evidence of ThermoDox’s Unique and Highly Effective Anti-Cancer Mechanism
“The findings published in Radiology serve as a companion paper to the groundbreaking work published by
A lysolipid thermally sensitive liposome encapsulating the chemotherapy agent, doxorubicin, ThermoDox®is designed to release targeted levels of doxorubicin into and around liver tumors with heat activation. The Phase I TARDOX study demonstrated that focused ultrasound exposure with ThermoDox® resulted in increased chemotherapy concentrations within liver tumors that were an average of 3.7 times greater than preheating levels across all 10 patients in the study.
“This latest publication of ThermoDox® clinical data emphasizes the significance and utility of its thermally activated delivery system and the high level of interest and support from the medical community for improved, targeted delivery of therapeutically potent levels of chemotherapy in patients with primary liver cancer, and potentially other cancers. Consistent with the
The Phase I TARDOX study evaluated patients with inoperable primary or secondary liver tumors who had previously received chemotherapy. In this trial, 10 patients received a single intravenous dose of 50 mg/m2 of ThermoDox®, and ultrasonic heating of target tumors was monitored in six participants using a minimally invasive temperature sensor, while four patients were treated without real-time thermometry. Safety was assessed by analysis of magnetic resonance imaging (MRI) and biopsy specimens for evidence of thermal ablation, as well as adverse event monitoring. There was no evidence of focused ultrasound-related adverse effects, including thermal ablation.
Numerous studies have demonstrated that focused ultrasound can be used to generate mild heating to facilitate the release of drug cargoes from thermosensitive liposomes (TSLs). We believe the TARDOX study is the world’s first Phase I clinical trial aimed at evaluating the effect of doxorubicin released from TSLs after focused ultrasound–induced mild hyperthermia. The study presents a model for predicting the focused ultrasound treatment parameters needed to attain mild hyperthermia and facilitate doxorubicin release from TSLs. This model may improve the current clinical use of hyperthermia by providing an alternative strategy for treatment planning based on a thermal model rather than actual thermometry, which is more invasive.
For all participants, CT images were used with the patient-specific hyperthermia model in order to define focused ultrasound treatment plans. Feasibility was assessed by comparing model-prescribed focused ultrasound powers to those implemented for treatment. The mean difference between predicted and implemented treatment powers was -0.1 W ± 17.7 SD. We believe this is a meaningful initial demonstration of the model providing accurate, successful treatment parameters. In addition, these observations support the potential for non-invasive hyperthermic ultrasound to expand the use of ThermoDox® to the treatment of other types of cancer.
The TARDOX study was carried out as a multi-disciplinary collaboration between
Celsion’s most advanced program is a heat-mediated, tumor-targeting drug delivery technology that employs a novel heat-sensitive liposome engineered to address a range of difficult-to-treat cancers. The first application of this platform is ThermoDox®, a lyso-thermosensitive liposomal doxorubicin (LTLD), whose novel mechanism of action delivers high concentrations of doxorubicin to a region targeted with the application of localized heat at 40°C, just above body temperature. In one of its most advanced applications, ThermoDox®, when combined with radiofrequency thermal ablation (RFA), has the potential to address a range of cancers. For example, RFA in combination with ThermoDox® has been shown to expand the “treatment zone” with a margin of highly concentrated chemotherapy when treating individual primary liver cancer lesions. The goal of this application is to significantly improve efficacy.
Celsion’s LTLD technology leverages two mechanisms of tumor biology to deliver higher concentrations of drug directly to the tumor site. The first: Rapidly growing tumors have leaky vasculature, which is permeable to liposomes and enables their accumulation within tumors. Leaky vasculature influences a number of factors within the tumor, including the access of therapeutic agents to tumor cells. Administered intravenously, LTLD is engineered to allow significant accumulation of liposomes at the tumor site at the time of radiofrequency ablation as these liposomes recirculate in the blood stream. The second: When the tumor tissue is heated to a temperature of 40°C or greater, the heat-sensitive liposome rapidly changes structure and the liposomal membrane selectively dissolves, creating openings that release the chemotherapeutic agent directly into the tumor and into the surrounding vasculature. Drug concentration increases as a function of the accumulation of liposomes at the tumor site, but only where the heat is present. This method targets only the tumor and the area related to tumor invasion, supporting precise drug targeting.
About the OPTIMA Study
The Phase III OPTIMA Study has enrolled 556 patients in over 60 clinical sites in
ThermoDox® is a registered trademark of
Source: Celsion CORP