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Drug-eluting Brachytherapy Implants for Chemo-radiation Therapy

用于放化疗的药物洗脱近距离放射治疗植入物

基本信息

批准号：
9908977
负责人：
SRINIVAS SRIDHAR
金额：
$ 100.72万
依托单位：
THERANANO, LLC
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-25 至 2021-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9908977
关键词：
Alternative Therapies American Animals Biocompatible Materials Brachytherapy Brachytherapy Seeds Cancer Etiology Cancer Patient Canis familiaris Cells Cessation of life Characteristics Clinic Clinical Collaborations Dana-Farber Cancer Institute Development Disease Disease-Free Survival Dose Drug Kinetics Drug Utilization Ensure Evaluation Fostering Foundations Head and Neck Cancer Hospitals I125 isotope Implant In Vitro International Lead Licensing Local Therapy Low Dose Radiation Malignant Neoplasms Malignant neoplasm of prostate Medical center Modality Modeling Mus Operative Surgical Procedures PC3 cell line Patients Pharmaceutical Preparations Phase Phase I Clinical Trials Process Property Prostate Prostate Cancer therapy Radiation Radiation Toxicity Radiation therapy Radiation-Sensitizing Agents Radiosensitization Reproducibility Risk Safety Science Site Small Business Technology Transfer Research Solvents Structure Technology Testing Therapeutic Therapeutic Effect Toxic effect Translating Translations Treatment Efficacy Tumor Suppression Universities Visual Weight Woman base cancer recurrence chemoradiation chemotherapy clinically relevant cohort combinatorial commercialization curative treatments docetaxel improved innovation manufacturing scale-up melting men mouse model pre-clinical radiosensitizing rectal response side effect success treatment strategy tumor

项目摘要

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.

Theranano LLC与国际知名的前列腺近距离治疗临床医生合作