A Study of ThermoDox™ in Combination With Radiofrequency Ablation (RFA) in Primary and Metastatic Tumors of the Liver
The purpose of this study is to determine the maximum tolerated dose (MTD) of ThermoDox when used in combination with radiofrequency ablation (RFA) in the treatment of primary and metastatic tumors of the liver.
Celsion has indicated that access to an investigational treatment associated with this study is available outside the clinical trial.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Dose Escalation Tolerability Study of ThermoDox™ (Thermally Sensitive Liposomal Doxorubicin) in Combination With Radiofrequency Ablation (RFA) of Primary and Metastatic Tumors of the Liver|
- To determine the maximum tolerated dose (MTD) of systemically delivered, heat-activated liposome encapsulated doxorubicin (ThermoDox) in combination with radiofrequency ablation (RFA) of liver neoplasms. [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]
- To test alternative infusion reaction prophylaxis regimens [ Time Frame: 48 hours ] [ Designated as safety issue: Yes ]
- To assess the safety of ThermoDox plus RFA afer administration of potential multiple cycles [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
- To determine the Pharmacokinetics (PK) of ThermoDox [ Time Frame: 48 hours ] [ Designated as safety issue: Yes ]
- To document any anti-tumor activity and assess recurrences. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- To measure post ablation lesion volume. [ Time Frame: 1 month ] [ Designated as safety issue: No ]
- To determine the cardiotoxicity of ThermoDox through enhanced ECG monitoring. [ Time Frame: 48 hours ] [ Designated as safety issue: Yes ]
|Study Start Date:||February 2007|
|Study Completion Date:||December 2009|
|Primary Completion Date:||October 2008 (Final data collection date for primary outcome measure)|
Ablative treatment approaches, such as RFA or microwave ablation, have received increased attention as alternates to other treatment approaches such as hepatic arterial embolization or chemoembolization (TACE) or percutaneous ethanol injection (PEI) in the majority of patients who are either not candidates for surgical resection or are not offered palliative supportive care only for diffuse disease. RFA can be applied repetitively to the same patient to treat multiple tumors at time of diagnosis or upon tumor recurrence (local or distant to the site of ablation), and is largely limited in its application only by tumor location and size (tumors near larger vessels, bowel or the hepatobiliary tree are more difficult to ablate). To extend the volume of the ablation region in a controlled fashion in patients and to improve the ability to kill tumor cells in the ablation margin region and allow for the improved treatment of HCC and MLC lesions > 3 cm in diameter by complete thermal ablation, Celsion Corporation has developed ThermoDox, a thermally sensitive, intravenously administered liposomal formulation of doxorubicin capable of selectively releasing its drug contents when exposed to temperatures of > 39.5°C. The concept behind this treatment approach is to create a large concentration gradient of doxorubicin in the immediate region of the tumor which borders the zone of RFA induced cell necrosis. The temperature isotherms produced in this boundary region should be adequate to activate doxorubicin release by the thermally sensitive liposomes deposited locally around the ablation zone. This in effect increases the region of tissue that can be treated beyond that achievable by RFA alone. Several clinical objectives are being tested in this study. The MTD for ThermoDox is to be confirmed. This study will assess the safety of using ThermoDox in conjunction with RFA over multiple cycles, consistent with the clinical needs of the subjects. While this study is not powered to define effectiveness of the combination of RFA plus ThermoDox, the results of this study should allow for an assessment of risk and benefit for designing future studies. This study will also test alternative infusion reaction prophylaxis regimens.