DIGNITY study data on ThermoDox in BCRCW presented at European congress
Celsion has presented Phase I results from its Phase I/II DIGNITY study of ThermoDox in breast cancer recurrences at the chest wall at the ESMO 2012 congress, the annual conference for the European Society of Medical Oncology held in Vienna, Austria. The presentation, entitled "Breast Cancer Recurrences at the Chest Wall (BCRCW) When Standard Treatments (Tx) Have Failed: Lyso-thermosensitive liposomal doxorubicin (LTLD) + Mild Local Hyperthermia (MLH)", was delivered by Professor Hope S Rugo, from the University of California San Francisco School of Medicine, and provided a clinical update of the trial studying ThermoDox for breast cancer.
In the Phase I portion of the DIGNITY study, a highly treatment-refractory BCRCW patient population was treated using ThermoDox in combination with MLH for superficial lesions <3cm depth that have failed standard treatment. The study was designed to determine the maximum tolerated dose (MTD) or confirm 50mg/m2 as acceptable, evaluate safety, sparse PK sampling and determine early effects of ThermoDox in combination with MLH. A total of 11 subjects were treated.
Drug-related adverse events were consistent with the known safety profile of doxorubicin including myelosuppression, alopecia, fatigue and nausea. Reversible myelosuppression was the most frequently observed effect, effectively managed with ASCO g-CSF treatment recommendations. Clinically meaningful responses were observed, including a target lesion response rate of 45 per cent without local progression (complete response 9.1 per cent, n=1/11, partial response 36.4 per cent, n=4/11). The study found that 50mg/m2 is the acceptable Phase II dose, as determined by independent review. Based on these results, Celsion is continuing into a Phase II study, to include additional clinical research sites.
ThermoDox is a heat-activated liposomal encapsulation of doxorubicin, an approved and frequently used oncology drug for the treatment of a wide range of cancers. In the HEAT study, ThermoDox is administered intravenously in combination with radiofrequency ablation (RFA). Localised mild hyperthermia (39.5 to 42 degrees Celsius) created by the RFA releases the entrapped doxorubicin from the liposome. This delivery technology enables high concentrations of doxorubicin to be deposited preferentially in a targeted tumour.
For primary liver cancer, ThermoDox is being evaluated in a global, multicentre, randomised, pivotal Phase III HEAT study at 79 clinical sites under an FDA SPA. The study is designed to evaluate the efficacy of ThermoDox in combination with RFA when compared with patients who receive RFA alone as the control. The primary endpoint for the study is progression-free survival with a secondary confirmatory endpoint of overall survival.