In Vivo Liquid Biopsy of Melanoma (Cytophone)

The Cytophone is a first in the world patented system to identify and count single circulating melanoma cells in blood circulation inside the human body. The Cytophone has a unique capability to find rare melanoma cells in the blood by an assessment of 100-500 times greater amounts of blood volume than routine blood tests. The important benefit of the Cytophone diagnosis is that the test does not require injection or any skin incision (i.e., non-invasiveness). The goal of this clinical trial is to demonstrate evidence of the capability of the Cytophone test to indicate a risk of metastasis and define CTC counts that correlate with melanoma recurrence, progression of metastatic disease, and therapy efficacy. The investigators believe that clinical trials will provide evidence that the Cytophone can diagnose risk of melanoma metastasis and recurrence earlier than existing methods.

The majority of melanoma deaths are associated with metastasis that are formed by cancer cells shedding from the primary tumor that enter the circulation and spread to distant organs via blood circulation. These cells in blood are referred to as circulating tumor cells (CTCs). Growing evidence suggests that metastasis is an early event in melanoma patients, often occurring before metastases are clinically detectable. Therefore, detection of CTCs using liquid biopsy assays should be considered as an effective tool to diagnose early the risk of metastasis progression. Taking into account the link of CTCs with metastasis, CTCs have an advantage over many other biomarkers in identifying patients for early therapeutic intervention at a stage when the disease is still manageable and possibly curable. Overall, CTCs are in the blood circulation in early stage disease, yet they are typically detected in later stage disease. Currently, the main issue restricting the use of CTCs for early melanoma detection relates to the low sensitivity of existing assays due to assessment of limited blood volume (i.e., blood samples in vitro). To maximize the blood volume available for analysis, in vivo CTC enumeration without labelling in a large blood volume using the Cytophone device was developed by our team. The Cytophone represents a photoacoustic (PA) flow cytometry (PAFC) diagnostic platform. Our feasibility clinical study has demonstrated the detection of CTCs in 49 of 50 melanoma patients (sensitivity 98%) and in 0 of 18 in healthy subjects (control group). The investigators received clinical evidence of the Cytophone's capability to diagnose 0.001 CTCs/mL which is significantly higher than sensitivity of existing testing methodologies. This threshold of the sensitivity is 130-times better than the sensitivity of the in vitro CellSearch (Menarini) assay which is only assay approved by FDA for clinical testing of CTCs (1 CTC in 7.5 mL; 0.13 CTCs/mL).

The Goal of this clinical study is to determine whether the Cytophone can be used for in vivo detection and enumeration of circulating tumor cells (CTCs) in the melanoma patients at different disease stages with focus on early diagnosis, early assessment of disease recurrence and monitoring of therapy efficiency. It is expected that the detection limit of CTCs will be improved at least an order of magnitude compared to the detection limits of existing methods. The test results are intended to use in conjunction with other clinical diagnostic methods.

The investigators hypothesize that our CTC assay, in vivo, provides earlier, rapid and more accurate diagnosis and prognosis of metastasis progression in melanoma patients. To achieve our goal, the investigators will accomplish the following primary and secondary objectives:

The primary objectives:

1. Obtain evidence that a positive Cytophone CTC test indicates a risk of metastasis development.
2. Define thresholds of CTC counts that correlate with melanoma recurrence and progression of metastatic disease.

The secondary objective:

1. Determine if the Cytophone diagnoses the risk of melanoma metastasis progression and recurrence earlier than existing methods.

Eligibility Criteria:
Inclusion Criteria:

* Histological documented diagnosis of melanoma;
* Participants having provided informed consent with signature on informed consent form: the informed consent process should be complete with full discussion of all requirements and possible risks;
* Must be able to sit for up to 60 minutes.

Exclusion Criteria:

* Unable to provide informed consent to participate in the study, such as a mental condition rendering the participant unable to understand the nature, scope, and possible consequences of the study;
* Clinically relevant cardiovascular, hepatic, neurological (e.g., evidence of organic brain syndrome), endocrine, or other major systemic disease making implementation of the protocol or interpretation of the study results difficult or that would put the participant at risk by participating in the study;
* Persistent significant or severe infection, either acute or chronic;
* Pregnant or breast-feeding women or those who plan to become pregnant during the study;
* Women of childbearing potential not protected by effective contraceptive method of birth control and/or who are unwilling or unable to be tested for pregnancy;
* Any known history of severe preexisting constipation.