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
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.
Interventional
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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.
1 month
Yes
United States: Food and Drug Administration
104-06-101-01
NCT00441376
February 2007
December 2009
Name | Location |
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Northshore Hospital - Long Island Jewish Health System | Manhasset, New York 11030 |