Clinical trial NCT06488365: In Vivo Liquid Biopsy of Melanoma (Cytophone)
Official title: In Vivo Liquid Biopsy for Early Detection of Metastatic Melanoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Melanoma
Circulating Tumor Cells
Metastatic Melanoma
Diagnosis
Keywords: melanoma
circulating tumor cells (CTCs)
in vivo liquid biopsy
metastasis
diagnosis and prognosis
Lead sponsor: Cytoastra
Sponsor class: INDUSTRY
First posted: 2024-07-05
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Healthy subjects and melanoma patients will be tested in this study. All subjects will receive the same Cytophone intervention (testing). Healthy subjects will receive one Cytophone test, and melanoma patients will receive four tests. There will be four cohorts to the study:

Cohort 1: 30 healthy subjects to address the calibration purpose. Cohort 2: 50 stage 0-I melanoma patients to link the presence of CTCs in blood circulation or increase in CTC count with metastatic disease initiation.

Cohort 3: 50 stage II melanoma patients to define the correlation between CTC count and metastatic disease initiation/progression and further recurrence.

Cohort 4: 50 stage III-IV melanoma patients to link CTC counts, metastatic disease progression and therapy efficiency.
Primary purpose: DIAGNOSTIC

Brief summary: 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.

Detailed description: 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.

Primary outcomes:
measure: Identify and count CTCs in blood in vivo
timeFrame: nine months
Secondary outcomes:
Other outcomes:
Locations:
city: Madison
country: United States
facility: SSM Health Dean Medical Group Specialty Services
state: Wisconsin
Study officials:
affiliation: Cytoastra
name: Ekaterina Galanzha, PhD
role: STUDY_DIRECTOR
References:
citation: Galanzha EI, Shashkov EV, Spring PM, Suen JY, Zharov VP. In vivo, noninvasive, label-free detection and eradication of circulating metastatic melanoma cells using two-color photoacoustic flow cytometry with a diode laser. Cancer Res. 2009 Oct 15;69(20):7926-34. doi: 10.1158/0008-5472.CAN-08-4900. Epub 2009 Oct 13.
citation: Galanzha EI, Zharov VP. Circulating Tumor Cell Detection and Capture by Photoacoustic Flow Cytometry in Vivo and ex Vivo. Cancers (Basel). 2013 Dec 10;5(4):1691-738. doi: 10.3390/cancers5041691.
citation: Galanzha EI, Menyaev YA, Yadem AC, Sarimollaoglu M, Juratli MA, Nedosekin DA, Foster SR, Jamshidi-Parsian A, Siegel ER, Makhoul I, Hutchins LF, Suen JY, Zharov VP. In vivo liquid biopsy using Cytophone platform for photoacoustic detection of circulating tumor cells in patients with melanoma. Sci Transl Med. 2019 Jun 12;11(496):eaat5857. doi: 10.1126/scitranslmed.aat5857.