Implantable Microdevice for the Delivery of Drugs and Their Effect on Tumors in Patients With Metastatic or Recurrent 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, and temsirolimus 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. Conditions Conditions: Metastatic Sarcoma Recurrent Sarcoma

• Doxorubicin (Drug), also known as Adriablastin, Hydroxydaunomycin, Hydroxyl Daunorubicin, Hydroxyldaunorubicin: Given via microdevice
• Doxorubicin Hydrochloride (Drug), also known as 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI), ADM, Adriacin, Adriamycin, Adriamycin Hydrochloride, Adriamycin PFS, Adriamycin RDF, ADRIAMYCIN, HYDROCHLORIDE, Adriamycine, Adriblastina, Adriblastine, Adrimedac, Chloridrato de Doxorrubicina, DOX, DOXO-CELL, Doxolem, Doxorubicin HCl, Doxorubicin.HCl, Doxorubin, Farmiblastina, FI 106, FI-106, hydroxydaunorubicin, Rubex: Given via microdevice
• Drug Delivery Microdevice (Device), also known as Microdevice: Undergo percutaneous implantation of drug delivery microdevice
• Everolimus (Drug), also known as 42-O-(2-Hydroxy)ethyl Rapamycin, Afinitor, Certican, RAD 001, RAD001, Votubia, Zortress: Given via microdevice
• Ganitumab (Biological), also known as AMG 479, Anti-IGF-1R Human Monoclonal Antibody AMG-479: Given via microdevice
• Ifosfamide (Drug), also known as Asta Z 4942, Asta Z-4942, Cyfos, Holoxan, Holoxane, Ifex, IFO, IFO-Cell, Ifolem, Ifomida, Ifomide, Ifosfamidum, Ifoxan, IFX, Iphosphamid, Iphosphamide, Iso-Endoxan, Isoendoxan, Isophosphamide, Mitoxana, MJF 9325, MJF-9325, Naxamide, Seromida, Tronoxal, Z 4942, Z-4942: Given via microdevice
• Irinotecan (Drug): Given via microdevice
• Pazopanib (Drug), also known as GW786034: Given via microdevice
• Polyethylene Glycol (Drug), also known as Glycol, polyethylene, PEG, Poly(oxyethylene), Polyethylene Glycol 400, Polyethylene Glycol 8000, POLYETHYLENE GLYCOL, UNSPECIFIED, Polyethylene Oxide: Given via microdevice
• Temozolomide (Drug), also known as CCRG-81045, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831, M and B 39831, Methazolastone, RP-46161, SCH 52365, Temcad, Temodal, Temodar, Temomedac, TMZ: Given via microdevice
• Temsirolimus (Drug), also known as CCI-779, CCI-779 Rapamycin Analog, Cell Cycle Inhibitor 779, Rapamycin Analog, Rapamycin Analog CCI-779, Torisel: Given via microdevice
• Therapeutic Conventional Surgery (Procedure): Undergo standard of care surgery
• Vincristine (Drug), also known as LEUROCRISTINE, VCR, Vincrystine: Given via microdevice

Primary outcomes

• Determination of the safety and technical feasibility of microdevice insertion/removal, as assessed by adverse events by CTCAE 5.0. [Up to 1 year]: Assess the safety of microdevice placement and removal in subjects undergoing resection of sarcoma.
• To assess efficacy across all individual agents or drug combinations tested using the microdevice technology. [Up to 1 year]: The primary outcome measure is the number of participants that experience a grade 3 or 4 adverse event, as defined by CTCAE 5.0. A second primary outcome measure of device technical feasibility measures the number of devices that successfully generate high-quality data from each of at least 50% of the patients enrolled. A successful device is one that generated high-quality data from at least 40% of the drugs in the device by IHC and/or other methodologies

Secondary outcomes

• Determine the drug antineoplastic drug effects observed in the adjacent tumor tissues following exposure to drug micro-doses released by each microdevice reservoir. [Up to 1 year]: The degree of cell apoptosis and cell proliferation observed in the adjacent tumor tissues will be compared for the placebo control (i.e. PEG) to gauge the antineoplastic effect elicited by each of the drug micro-doses released by the respective microdevice reservoirs.

Sex: All, ages: 10 Years to any

Inclusion:

* Patients with a biopsy-confirmed recurrent or metastatic sarcoma for which surgery is indicated as a standard of care.
* 10 years of age or older
* Documented, signed, dated informed consent to participate in the microdevice study
* Eastern Cooperative Oncology Group (ECOG) performance status of =< 2

Exclusion:

* Subjects who do not wish to undergo surgical resection, or those who are high-risk or not candidates for surgical resection
* Age < 10 years old
* Women of childbearing potential without a negative pregnancy test; or women who are lactating
* Allergies or prior adverse drug reactions to any of the drugs loaded within the microdevice.

• Informed Consent Form (PDF, 2024-08-26)

• Joseph Ludwig, MD, Principal investigator, M.D. Anderson Cancer Center

NIH grants: R01CA180279