Date: 2014-09-08
Type of information: Presentation of results at a congress
phase: 3
Announcement: presentation of results at the International Liver Cancer Association 2014 Annual Conference
Company: Celsion (USA - NJ)
Product: ThermoDox® (encapsulated doxorubicin) in combination with standardized radiofrequency ablation (sRFA)
Action
mechanism: antineoplastic agent. Using its LTSL (lysolipid thermally sensitive liposomes) technology, Celsion has encapsulated doxorubicin to create ThermoDox®. The heat-sensitive liposome rapidly changes structure when heated to a specific temperature, creating openings in the liposome which release doxorubicin directly into the targeted tumor. ThermoDox®, delivered by IV infusion, is designed to be used in combination with hyperthermic (heat-based) treatments, such as radiofrequency thermal ablation (RFA), microwave hyperthermia and high intensity focused ultrasound (HIFU). ThermoDox® leverages two mechanisms of tumor biology to deliver higher concentrations of drug directly to the targeted tumor site. First, tumors have leaky vasculature, which is permeable to liposomes and enables their accumulation within tumors. Second, when heated, blood vessels in tumors become even more permeable, further increasing the accumulation of liposomes in tumors before releasing the drug payload. The potential of this approach has been demonstrated in vivo; in animal models, ThermoDox® has been shown to deliver 25 times more doxorubicin than IV doxorubicin into tumors, and five times more doxorubicin than standard liposomal formulations of the drug.
Disease: hepatocellular carcinoma
Therapeutic area: Cancer - Oncology
Country: USA, Europe, China, Asia Pacific
Trial
details: Celsion's Phase III OPTIMA Study is a global pivotal, double-blind, placebo-controlled study evaluating ThermoDox®, its proprietary heat-activated liposomal encapsulation of doxorubicin, in combination with radiofrequency ablation (RFA) in HCC. The study is expected to enroll 550 patients globally, with up to 100 sites in the United States, Europe, China and Asia Pacific. (NCT02112656)
Latest
news: * On September 8, 2014, Celsion announced highlights from three presentations by three of the world's leading liver cancer experts and principal investigators for the Company's pivotal Phase III OPTIMA Study of ThermoDox®, Celsion's proprietary heat-activated liposomal encapsulation of doxorubicin, in combination with standardized radiofrequency ablation (sRFA) in primary liver cancer (hepatocellular carcinoma - HCC). The presentations were made by Ronnie T.P. Poon, MD, MS, PhD, FRCS (Edin), FACS, Professor of Surgery at the University of Hong Kong Queen Mary Hospital, Lead Asia Pacific Principal Investigator for Celsion's Phase III OPTIMA Study and member of the ILCA Governing Board. Professor Poon's presentation, titled "New Paradigms in Staging HCC: BCLC vs. Hong Kong Liver Cancer Staging System (HKLS)," covered a more aggressive strategy for treating different stages of HCC. Intermediate stage HCC may be curable with RFA and combining sRFA with ThermoDox® may enhance the cure rate. Richard S. Finn, MD, faculty at the Division of Hermatology and Oncology and Director of the Translational Oncology Research Laboratory at UCLA, North American Principal Investigator for Celsion's Phase III OPTIMA Study and member of the ILCA Governing Board. Dr. Finn's presentation, titled "Phase III Studies in Intermediate Stage HCC: What Have We Learned From Recent Failures?" reviewed results from recent Phase III clinical studies in intermediate stage HCC patients including recent overall survival data from Celsion's Phase III HEAT Study post-hoc analysis, noting a subgroup of significant size, strongly suggests positive Overall Survival (OS) in ThermoDox® treated patients when heating cycles from the radiofrequency ablation (RFA) procedure were optimized. As of June 30, 2014, data from the latest HEAT Study post-hoc analysis continued to show that ThermoDox® may significantly improve overall survival compared to a RFA control in patients whose lesions undergo RFA treatment for 45 minutes or more. These findings apply to patients with single HCC lesions (64.4% of the HEAT Study population) from both size cohorts of the HEAT Study (3-5 cm and 5-7 cm) and represent a subgroup of 285 patients. For this group, clinical results indicate a 57% improvement in Overall Survival, a Hazard Ratio of 0.639 (95% CI 0.419 - 0.974), and a p-value of 0.037. Riccardo Lencioni, MD, FSIR, EBIR, Professor and Director of the Division of Diagnostic Imaging and Intervention at Pisa University School of Medicine in Pisa, Italy and Lead European Principal Investigator for Celsion's Phase III OPTIMA Study.
Dr. Lencioni's presentation, titled "Image Guided Ablations: Current Status and Future Prospects," reviewed findings from the HEAT Study post-hoc analysis which strongly support the rationale for a minimum 45 minute ablation time when using ThermoDox®. The findings from the HEAT study suggest that there could be an important curative role for RFA and ThermoDox® in intermediate HCC if a 45 minute heating time is applied. "Results from the HEAT Study, among the largest clinical trials conducted in primary liver cancer, highlight the important potential of ThermoDox® in this indication and underscores the need to standardize RFA with ThermoDox®," said Professor Lencioni. "The HEAT Study clearly demonstrated that there is a place for RFA in treating intermediate HCC and standardizing RFA with ThermoDox®, as in Celsion's OPTIMA Study, may be the key to a curative treatment for this deadly cancer."
