Implantable Microdevice for the Delivery of Drugs and their Effect on Tumors in Patients with Sarcoma

PRIMARY OBJECTIVES:

I. Assess the safety of drug delivery microdevice (microdevice) placement and removal in subjects undergoing resection of sarcoma.

II. Determine the technical feasibility of microdevice placement and removal with intact surrounding tissue in subjects undergoing resection of a sarcoma.

SECONDARY OBJECTIVE:

I. Use the intratumoral cellular response to evaluate individual agents and/or drug combinations released from the microdevice reservoirs to assess the relative drug efficacy across all individual agents or drug combinations tested using the microdevice technology.

EXPLORATORY OBJECTIVES:

I. Evaluate the microdevice performance for its capacity to predict Response Evaluation Criteria in Solid Tumors (RECIST) response in the subset of patients that receive systemic chemotherapies as part of their standard-of-care or clinical trial treatments.

II. Determine genomic, transcriptomic, and proteomic predictive biomarkers from resected specimens that correlate with local (i.e. microdevice-based) and systemic drug response.

III. Determine, at a single-cell level, proteomic traits associated with chemosensitivity versus (vs.) resistance using mathematical notions of network robustness and fragility.

OUTLINE:

Patients undergo percutaneous implantation of up to 3 drug delivery microdevices up to 2 days before standard of care surgery. Patients receive doxorubicin hydrochloride, ifosfamide, vincristine, irinotecan, temozolomide, pazopanib, everolimus, polyethylene glycol, ganitumab, temsirolimus, alpelisib, cyclophosphamide, dacarbazine, docetaxel, etoposide, gemcitabine, methotrexate, selinexor, locnartecan, paclitaxel, Ets-family transcription factor inhibitor TK216 via the microdevice in the absence of unacceptable toxicity. At the time of surgery 2 days later, patients have the drug delivery microdevice(s) removed.