This is a first-in-human, single-arm, open-label, dose escalating study to determine the safety and the recommended maximum tolerated dose of the AMT in subjects with malignant cutaneous lesions. AMT is a combination therapy of a drug (IUdR) and a device (AUTRON Therapy System). IUdR is an iodinated thymidine analogue that is preferentially incorporated into DNA in rapid growing cells. The AUTRON Therapy System generates characteristic X-Ray photons around 33.4 keV, matching the K-edge energy of Iodine (33.17 keV), which can efficiently induce Auger electron emissions from IUdR in cancer DNA, resulting in extensive DNA damage and cancer cell death.
NanoRay Biotech is developing a novel investigational therapeutic system called Auger Molecular Therapy (AMT), which consists of a drug, Iododeoxyuridine (IUdR), and a medical device, AUTRON Therapy System, intended for the palliative treatment of malignant cutaneous lesions. IUdR is an iodinated analogue of deoxyuridine, which can be incorporated into DNA of cancer cells because it is a thymidine analogue. The AUTRON Therapy System is a complete, standalone low energy X-Ray radiation source (80 kVp, 100 μA) intended for local irradiation. The AUTRON Therapy System contains a novel design of transmission type X-Ray tube, which allows electron beams to pass through the metal target and generates characteristic X-Ray similar to synchrotron radiation. The combination product is intended to induce Auger effect to augment the damage on tumor cells, while lowering the adverse effect on normal cells. IUdR is an iodinated thymidine analogue that is preferentially incorporated into DNA in rapid growing cells (such as cancer cells) after administration. The AUTRON Therapy System generates characteristic X-Ray photons around 33.4 keV, matching the K-edge energy of Iodine (33.17 keV), which can efficiently induce emissions of Auger electrons when hitting the Iodine atoms on IUdR in cancer DNA, resulting in extensive DNA damage and cancer cell death. Furthermore, the characteristic X-Ray photons generated by the AUTRON Therapy System have a low penetration rate in biological materials, which give the maximum dose on superficial lesions and much reduced dose on peripheral or deep normal tissues, fitting the need on the management of malignant cutaneous lesions.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
18
The AMT consists of intratumorally delivered IUdR and local irradiation via AUTRON Therapy System.
Taipei Medical University Hospital
Taipei, Taiwan
RECRUITINGLesion severity
In this trial, local lesion assessment will be carried out by a simplified Modified Severity Weighted Assessment Tool (mSWAT) without %BSA parameter, since the AMT is applied only on local and single lesion. A local skin scoring by area with a multiplication by weighting factors of various lesion types (patch=1, plaque=2 and tumor=4) is applied for mSWAT evaluation.
Time frame: 56 weeks from Day -1 predose
Improvement of quality of life
The Taiwanese version of the McGill Quality of Life Questionnaire (MQOL) consists of 16 items, global QOL questions and open-ended questions allowing patients to self-report life events that have influenced their QOL. There are four parts in MQOL: physical symptoms (items 1-4), psychological well-being (items 5-8), existential well-being (items 9-14), and support issues (items 15 and 16). All of the response categories are based on a numerical scale of from 0 to 10. The all score will be divided into four parts and a high score indicates a better QOL.
Time frame: 8 weeks from Day -1 predose
Assess the drug safety during treatment
Safety evaluation will be based on the percentage of subjects with dose-limiting toxicity (DLT), adverse events (AE), and serious adverse events (SAE). Toxicity will be classified by National Cancer Institute's Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0).
Time frame: 4 weeks of treatment cycle
Assess the drug safety post-treatment
Safety evaluation will be based on the percentage of subjects with dose-limiting toxicity (DLT), adverse events (AE), and serious adverse events (SAE). Toxicity will be classified by National Cancer Institute's Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0).
Time frame: 4 weeks post treatment
Local control of lesion
The lesion condition change is evaluated by CT before and after treatment.
Time frame: 12 weeks
Systemic immune response
Evaluated by changes in composition of peripheral lymphocytes in patient blood samples.
Time frame: 56 weeks
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