Date: 2014-09-04
Type of information: Publication of results in a medical journal
phase: 1
Announcement: publication of results in the International Journal of Hyperthermia
Company: Celsion (USA - NJ)
Product: ThermoDox® (encapsulated doxorubicin)
Action
mechanism: 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: recurrent chest wall breast cancer
Therapeutic area: Cancer - Oncology
Country: USA
Trial details:
Latest
news: * On September 4, 2014, Celsion announced that data from two Phase I studies on ThermoDox® in recurrent chest wall breast cancer were published in the International Journal of Hyperthermia. The article describes the combined results of the two similarly designed Phase I trials with one study conducted at Duke University and the second study conducted at other major breast cancer centers in the U.S., in which eligible patients with unresectable chest wall recurrences had progressed on the chest wall after prior hormone therapy, chemotherapy, and radiotherapy. Patients received up to six cycles of ThermoDox® every 21-35 days, followed immediately by chest wall mild local hyperthermia for 1 hour at 40-42°C. In the first trial, 18 subjects received ThermoDox® at 20, 30, or 40 mg/m²; in the second trial, 11 subjects received ThermoDox® at 40 or 50 mg/m². The results showed that the maximum tolerated dose was 50 mg/m². The rate of overall local response was 48%, with five patients (17%) achieving complete local responses and nine patients (31%) having partial local responses. It was concluded that ThermoDox® at 50 mg/m² and mild local hyperthermia was safe, and this combined therapy produces objective responses in heavily pretreated RCWBC patients. Importantly, these Phase I data are consistent with the impressive interim results from Celsion\'s ongoing open-label Phase II DIGNITY Study of ThermoDox® in RCWBC. The DIGNITY Study will enroll a minimum of 20 patients at several U.S. clinical sites and is evaluating ThermoDox® in combination with mild hyperthermia using a treatment design equivalent to that used in the Phase I programs. Of the 13 patients enrolled and treated, 10 were eligible for evaluation of efficacy. Based on data available to date, 60% of patients experienced a stabilization of their highly refractory disease with a local response rate of 50% observed in the 10 evaluable patients, notably 3 complete responses (CR), 2 partial responses (PR) and 1 patient with stable disease (SD). The article, titled \"Two phase 1 dose-escalation/pharmacokinetics studies of low temperature liposomal doxorubicin (LTLD) and mild local hyperthermia in heavily pretreated patients with local regionally recurrent breast cancer,\" appears in the August 2014 issue (Volume 30, Number 5).
