The overall objective of this SBIR Phase 1 grant is to finalize the formulation design for a carboplatin-loaded Low Temperature Sensitive Liposome (LTSL-carboplatin) and demonstrate the effectiveness of the optimized product combined with HyperThermia (HT), to kill cells in a melanoma target cancer cell line. The work is motivated by the fact that of the 1.4 million new cases of cancer expected in 2009, over 0.5 million cases could be treated with platinum based therapies. With a thermal sensitive liposomal product containing doxorubicin, (LTSL-Dox, or ThermoDox(R)) already in Phase I/II human clinical trials for recurrent chest wall, and Phase III human clinical trials (with a special protocol assessment from the FDA) for hepatocellular carcinoma, we want to introduce a second anti-cancer agent, carboplatin, that is not only chemotherapeutic but is also a radiation sensitizer.
The specific Aims of the proposal are: SA1: To prepare batches of LTSL-carboplatin and characterize its drug and lipid stability, thermal, drug loading, drug leakage, and triggered release profiles as a function of temperature and liposome composition;SA2: Compare Paraplatin(R) (carboplatin injection) and LTSL-carboplatin in a single tumored mouse model. These studies will lay the foundation for a Phase 2 SBIR in which the time course of drug and HT application will be further investigated to optimize clinical protocols and to allow well-informed choices to be made for subsequent human clinical trials. The medicinal value for this heat activated drug is expected to be an improvement in the local therapy of a number of oncology indications (metastatic melanoma, kidney, pancreatic, ovarian, lung, head &neck, bladder and esophageal) that platinum agents may address.
This project proposes to extend Celsion's heat sensitive liposome platform technology, which currently has a drug (ThermoDox(R)) in Phase III liver cancer clinical trials, to include a thermally sensitive liposome encapsulating carboplatin, for potential development into a clinical program for the treatment of metastatic melanoma. The two aspects of the project include 1) a formulation design and optimization study conducted to engineer desired bio-performance characteristics with the goal of accomplishing targeted drug release when dosing is accompanied by thermal warming of the tumor site, and 2) subsequent efficacy evaluations in a xenograft tumored mice model for the subject cancer. A new liposome encapsulated carboplatin is anticipated to greatly benefit cancer patients as the encapsulation and targeted delivery is expected to result in a superior safety, tolerance, and toxicity profile.
