Theranano LLC in collaboration with internationally renowned prostate brachytherapy clinicians at Brigham and Womens Hospital and Dana Farber Cancer Institute and biomaterials experts at Northeastern University have developed an innovative combinatorial treatment strategy of Local ChemoRadiation Therapy (LCRT) using a modified brachytherapy spacer platform in the form of a INCeRT (ImplaNts for ChemoRadiation Therapy) spacer loaded with Docetaxel (DTX) to locally radiosensitize the prostate, enabling a synergistic cure with the use of lower radiation doses, thereby leading to less rectal radiation toxicity and minimal chemotherapeutic systemic side effects. Extensive results have demonstrated the efficacy and safety of the technology: (i) As monotherapy, in PC3 tumored mice, therapeutic doses of DTX can be delivered using intratumoral INCeRT spacers that lead to complete tumor suppression and disease free survival in 90% of animals. (ii) DTX-loaded INCeRT spacers show sustained synergistic radiosensitization. (iii) For combined LCRT, sustained DTX release prolongs the tumor suppression in irradiated mice. (iv) Toxicity as assessed by gross weight, and visual observation, is greatly reduced compared with IV administration of equivalent doses of DTX. These results have demonstrated the validity and feasibility of LCRT using INCeRT spacers. The Phase I STTR project demonstrated the feasibility of a solvent free hot-melt extrusion process of fabrication of InCeRT DTX spacers thus providing proof-of-principle of reproducible scale-up of manufacturing of INCeRT spacers. The HME spacers fabricated possessed all the desired material and drug characteristics, as well as in vitro release, PrCa model efficacy and toxicity profiles, achieving all the aims of the project. The Phase I project met and exceeded all its aims. In this Phase II STTR project Theranano will partner with outstanding collaborators to carry out IND-enabling GLP level manufacture and pre-clinical animal studies through the following aims:
Specific Aim 1 : Fabricate GLP quality InCeRT-DTX brachytherapy spacer implants GLP level manufacture of InCeRT-DTX implants will be carried out. The GLP implants will be thoroughly characterized for their physico-chemical properties.
Specific Aim 2 : Non-GLP therapeutic efficacy of INCeRT spacers in clinically relevant PCa mice models. The implant spacers fabricated in SA1 will be tested for release and therapeutic efficacy in PC3 cells and tumor models to ensure their bioactivity.
Specific Aim 3 : IND-enabling GLP pharmacokinetics and toxicity evaluation of INCeRT implants with brachytherapy in canine models. GLP level animal studies in canine models will be carried out for demonstrating the safety of the InCeRT-DTX implants in conjunction with I125 brachytherapy seeds.
Specific Aim 4 : Submission of FDA IND application An FDA IND application will be submitted and planning for a Phase I clinical trial will be initiated.
TITLE: Drug-eluting Brachytherapy Implants for Chemo-radiation Therapy This STTR phase II project seeks to translate drug-eluting brachytherapy implants for Local Chemo-Radiation Therapy (LCRT) as a new modality of prostate cancer treatment. LCRT combines radiation therapy with chemotherapy delivered locally to the prostate, utilizing drug releasing spacers similar to those currently used in brachytherapy, to boost the overall treatment efficiency while greatly reducing toxic side effects. The treatment has the potential to improve the lives of all of the thousands of men with localized prostate cancer who are treated each year with radiation therapy.
