Date: 2014-07-28
Type of information: Interim results
phase: 2
Announcement: interim results
Company: Celsion (USA - NJ)
Product: ThermoDox® (encapsulated doxorubicin) in combination with radiofrequency ablation
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: primary liver cancer
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: * On August 6, 2015, Celsion Corporation, an oncology drug development company, announced updated results from its retrospective analysis of the Company's 701-patient HEAT Study of ThermoDox®, Celsion's proprietary heat-activated liposomal encapsulation of doxorubicin in combination with radiofrequency ablation (RFA) in hepatocellular carcinoma (HCC). As of July 15, 2015, the latest overall survival (OS) analysis demonstrated that in a large, well bounded, subgroup of patients (n=285, 41% of the HEAT Study patients), treatment with a combination of ThermoDox® and optimized RFA provided an average 58% improvement in OS compared to optimized RFA alone. The Hazard Ratio (HR) at this analysis is 0.63 (95% CI 0.43 - 0.93) with a p-value of 0.0198. Median overall survival for the ThermoDox® group has been reached which translates into a 25.4 month (2.1 year) survival benefit over the optimized RFA group (79 months for the ThermoDox® plus optimized RFA group versus 53.6 months for the optimized RFA only group). In the most recent post-hoc analysis of the HEAT Study, data continued to support and further strengthen ThermoDox®'s potential to significantly improve OS compared to an RFA control in patients with lesions that undergo optimized RFA treatment for 45 minutes or more. Findings from this analysis 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), representing a subgroup of 285 patients. Additional findings from this most recent analysis specific to the Chinese cohort of patients with single lesions (74% of the HEAT Study Chinese patient population) showed a 75% improvement (HR = 0.57 with a p-value of 0.08) in OS for the ThermoDox® plus optimized RFA group compared to optimized RFA only group. Patients in the Chinese cohort with single lesions between 3-5 cm showed a doubling of improvement (HR = 0.50 with a p-value of 0.06) in OS when treated with ThermoDox® plus optimized RFA. * On July 28, 2014, Celsion announced updated results from its retrospective analysis of the Company's 701-patient HEAT Study of ThermoDox®, Celsion's proprietary heat-activated liposomal encapsulation of doxorubicin, in combination with radiofrequency ablation (RFA) in primary liver cancer, also known as hepatocellular carcinoma (HCC). As of June 30, 2014, the latest quarterly Overall Survival (OS) analysis demonstrated that in a large, well bounded, subgroup of patients (n=285, 41% of the study patients), the combination of ThermoDox® and optimized RFA provided a 57% improvement in OS compared to optimized RFA alone. The Hazard Ratio at this analysis is 0.639 (95% CI 0.419 - 0.974) with a p-value of 0.037. These data continue to strongly suggest that ThermoDox® may significantly improve OS 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 OS, a Hazard Ratio of 0.639 (95% CI 0.419 - 0.974), and a p-value of 0.037. The HEAT Study and prior post-hoc analyses were presented at multiple medical conferences over the past year, including: the 2014 American Society of Clinical Oncology 50th Annual Meeting in June 2014; the 5th European Conference on Interventional Oncology in April 2014; the International Liver Cancer Association Annual Conference in September 2013; the European Conference on Interventional Oncology in June 2013; and the World Conference on Interventional Oncology in May 2013. Presentations were made by some of the most highly recognized liver cancer researchers and key HEAT Study investigators. Quarterly overall survival data analyses have been conducted with the full support of these researchers and clinical investigators. Currently, a Phase III OPTIMA Study in primary liver cancer is evaluating ThermoDox® in combination with a standardized RFA protocol in primary liver cancer (NCT02112656)
