Drug-eluting Brachytherapy Implants for Chemo-radiation Therapy

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Prostate cancer (PCa) is the second leading cause of cancer death in American men, with 26,130 deaths and 161,360 new cases estimated in the US in 2017. Radiation therapy is one of the standard therapies for high and intermediate risk patients, and is a non-surgical therapy option for low risk patients. A combined chemo-radiation therapy (CRT) approach has been shown in several trials to improve survival in multiple cancers, compared with monotherapies. However, systemic chemotherapy accompanying CRT typically come at the price of increased toxicity and thus require synchronization of the two modalities to achieve maximum benefit. Here, an immediate need exists to deliver the drug specifically at tumor site in locally recurrent patients while avoiding toxicities associated with systemic delivery and resulting in preferential radiosensitization of the prostate compared to the normal structures. Northeastern University and Theranano LLC in collaboration with clinicians at Brigham and Womens Hospital and Dana Farber Cancer Institute have developed an innovative combinatorial treatment strategy of Local Chemo-Radiation 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. These new INCeRT spacers are physically similar to the inert spacers routinely used in prostate brachytherapy but now loaded with formulations of DTX which can be tuned to release the drug payload from a week to several months. The technology has been exclusively licensed to TheraNano LLC for commercialization and translation to the clinic. The phase 1 project goals will be achieved through the following specific aims: Specific Aim 1: Development, scale up and quality control of docetaxel loaded INCeRT brachytherapy spacers. Develop INCeRT brachytherapy spacers loaded with DTX with analysis of quality control, reproducibility, drug loading and drug release using optimized SOPs. Earlier work at Northeastern University has produced INCeRT spacers in batches of <20. Here, we plan to scale-up the process to routinely manufacture DTX INCeRT spacers in batches of several 100s in GLP conditions. The study design will include setting up a pilot plant for fabrication, characterization of INCeRT spacers loaded with docetaxel and quality control assessment in terms of reproducibility, size, drug loading and release kinetics under GLP conditions. Specific Aim 2: In vivo therapeutic efficacy of combined Chemo-Radiation treatment and toxicity assessment in Prostate cancer models. We will evaluate the therapeutic efficacy of INCeRT spacers combined with Brachytherapy/EBRT by locally implanting the spacers at the tumor site in PCa animal models. We will also assess gross immunotoxicity associated with the combined treatment.