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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Single Arm | Experimental | Subjects will have the device placed loaded with chemotherapeutic agents. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Doxorubicin, FOLFOX, Botensilimab, Balstilimab, Bevacizumab, FOLFIRI, FOLFIRINOX, AGEN2373 | Combination Product | Patients 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 12 months |
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Inclusion Criteria:
Normal organ and marrow function, defined as follows:
Males and females of childbearing potential must agree to use effective contraception starting before the first day of treatment and continuing for at least 3 months (men) or 6 months (women) after implantation of the microdevice. Additionally, due to the unknown but potential risks of nursing infants secondary to the treatment of the mother with the chemotherapeutic agents of the study, mothers must agree to discontinue breastfeeding for a total of 14 days after the insertion of the microdevice.
Exclusion Criteria:
Tumor location not amenable to device placement Pregnancy at the time of enrollment or operation due to the known teratogenicity of the medications involved.
Prior or concurrent second primary malignancy whose natural history or treatment has the potential to interfere with the safety or primary endpoint efficacy assessment of the CLM Extra-hepatic disease or unresectable liver metastasis on baseline imaging
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Micaela Wigfall Maxwell | Contact | 833-223-4732 | MWigfallMaxw@northwell.edu |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| RJ Zuckerberg | Recruiting | Lake Success | New York | 11042 | United States |
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|
| Long Island Jewish Medical Center | Recruiting | New Hyde Park | New York | 11040 | United States |
|
| ID | Term |
|---|---|
| D004317 | Doxorubicin |
| C410216 | Folfox protocol |
| C000720935 | balstilimab |
| D000068258 | Bevacizumab |
| C000627770 | folfirinox |
| ID | Term |
|---|---|
| D003630 | Daunorubicin |
| D018943 | Anthracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
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