Microdevices have been used to ascertain in vivo drug response, which can lead to improved cancer treatment delivery; however, they have not been evaluated for liver tumors. This is a prospective, phase 1 safety study of percutaneous placement and surgical retrieval of a microdevice in patients with liver metastasis from colorectal cancer. The device will be implanted percutaneously 3-5 days prior to scheduled resection of colorectal liver metastasis (CLM) and then removed en bloc with the tumor. Patients will be monitored to ensure that the device's placement and retrieval does not result in increased complication rates within 14 days of surgery. To assess feasibility, the tissue surrounding the microdevice will be analyzed to assess the diffusion of the drugs from the device into the tissue and whether the therapeutic effect of diffusing chemotherapy +/- immune-modulating drugs has an impact on the surrounding tissue.
Histologically confirmed colorectal cancer with suspicion of liver metastasis on imaging Liver tumor ≥2 cm on preoperative imaging via computed tomography (CT) or magnetic resonance imaging (MRI) Planned hepatectomy as part of standardized treatment plan, irrespective of study enrollment ≥18 years of age
Leukocytes ≥3,000/mcL
Absolute neutrophil count ≥1500/mcL
Platelets ≥ 100,000/mcL
None
Single group
Doxorubicin, FOLFOX, Botensilimab, Balstilimab, Bevacizumab, FOLFIRI, FOLFIRINOX, AGEN2373
Combination productPatients with diagnosed liver metastasis from a colorectal primary deemed resectable. The study intervention will be limited to the percutaneous placement of up to 2 IMDs per lesion with a maximum of 4 devices total, with the subsequent en bloc resection of the tumor plus IMD within 3 (+2) days after placement. The microdevices will remain in the tumor for a minimum of a 2-day incubation period, although ideally for 3 days. The IMD is a small cylindrical device approximately 750 um in diameter and 5 mm in length (Figure 2), housing up to 21 reservoirs. It is made of PEEK, biocompatible material used in other implantable constructs, including joint replacements. 11-13 Drugs are solubilized with poly-ethylene glycol (PEG) and loaded into the individual reservoirs. The drug diffusion has been mapped extensively to ensure that the weight of PEG is selected such that drug diffusion is limited and will not mix or interfere with another drug.
Incidence of adverse events (AEs) associated with Microdevice placement and retrieval
To evaluate the safety of microdevice placement and retrieval based on assessment of adverse events. AEs will be defined using Common Terminology Criteria for AEs (CTCAE) v5.0 Any device resulting in either of the following will be considered a failure from a safety standpoint: any listed SAE two or more grade 3-4 AEs directly associated with the device or its placement Significant delay in the standard hepatic resection of more than 14 days due to device-related complications Safety will be evaluated on a per-patient level, where an event is defined as any "failure" observed among all devices. This is a phase 1 pilot safety trial that must only demonstrate the ability to perform this procedure without undue risk
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