Implantable Microdevice for the Delivery of Drugs and Their Effect on Tumors in Patients With Metastatic or Recurrent Sarcoma

Study Overview
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Brief Summary
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This early phase I trial studies the side effects of implanting and removing a microdevice in patients with sarcomas that have spread to other places in the body (metastatic) or have come back (recurrent). Microdevices are rice-sized devices that are implanted into tumor tissue and are loaded with 10 different drugs that are delivered at very small doses, or microdoses, which may only affect a very small, local area inside the tumor. The purpose of this study is to determine which drugs delivered in the microdevice affect tumor tissue in patients with sarcomas.

Detailed Description
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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

Official Title
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Pilot Trial of an Implantable Microdevice for In Vivo Drug Sensitivity Testing in Patients With Sarcomas

Conditions
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Metastatic Sarcoma, Recurrent Sarcoma, Resectable Sarcoma

Intervention / Treatment
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* Drug: Doxorubicin
* Drug: Doxorubicin Hydrochloride
* Device: Drug Delivery Microdevice
* Drug: Everolimus
* Biological: Ganitumab
* Drug: Ifosfamide
* Drug: Irinotecan
* Drug: Pazopanib
* Drug: Polyethylene Glycol
* Drug: Temozolomide
* Drug: Temsirolimus
* Procedure: Therapeutic Conventional Surgery
* Drug: Vincristine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 10 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Device Feasibility (microdevice, surgery)<br>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. | Drug: Doxorubicin<br>* Given via microdevice<br>* Other names: Hydroxyldaunorubicin;Drug: Doxorubicin Hydrochloride<br>* Given via microdevice<br>* Other names: Rubex;Device: Drug Delivery Microdevice<br>* Undergo percutaneous implantation of drug delivery microdevice<br>* Other names: Microdevice;Drug: Everolimus<br>* Given via microdevice<br>* Other names: Zortress;Biological: Ganitumab<br>* Given via microdevice<br>* Other names: Anti-IGF-1R Human Monoclonal Antibody AMG-479;Drug: Ifosfamide<br>* Given via microdevice<br>* Other names: Z-4942;Drug: Irinotecan<br>* Given via microdevice<br>Drug: Pazopanib<br>* Given via microdevice<br>* Other names: GW786034;Drug: Polyethylene Glycol<br>* Given via microdevice<br>* Other names: Polyethylene Oxide;Drug: Temozolomide<br>* Given via microdevice<br>* Other names: TMZ;Drug: Temsirolimus<br>* Given via microdevice<br>* Other names: Torisel;Procedure: Therapeutic Conventional Surgery<br>* Undergo standard of care surgery<br>Drug: Vincristine<br>* Given via microdevice<br>* Other names: Vincrystine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of the safety and technical feasibility of microdevice insertion/removal, as assessed by adverse events by CTCAE 5.0. | Assess the safety of microdevice placement and removal in subjects undergoing resection of sarcoma. | Up to 1 year | 
| To assess efficacy across all individual agents or drug combinations tested using the microdevice technology. | 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 | Up to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the drug antineoplastic drug effects observed in the adjacent tumor tissues following exposure to drug micro-doses released by each microdevice reservoir. | 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. | Up to 1 year |