Clinical trial NCT06710093: Power of Liquid Biopsy Tracking in Immunotherapy Treated Stage IV Melanoma
Official title: Power of Liquid Biopsy Tracking in Immunotherapy Treated Stage IV Melanoma
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Metastatic Melanoma
Keywords: ctDNA testing
advanced melanoma
immune checkpoint inhibitors (ICI)
Lead sponsor: Royal Marsden NHS Foundation Trust
Sponsor class: OTHER
First posted: 2024-11-29
Enrollment: 100
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients are being enrolled from either relapsed unresectable Stage III or Stage IV melanomas

Brief summary: The advent of immune ICI has remarkably improved survival in advanced melanoma patients in the last decade. Long term responders following 2 years of treatment with immunotherapy go on to surveillance with frequent radiological imaging every 3-6 months up to 5-10 years. This not only exposes patients with a relatively low risk of recurrence to significant amounts of ionising radiation, but also increases the burden and cost on already stretched radiology departments. Therefore, this study aims to assess the feasibility and patient experience of using ctDNA with minimally invasive liquid biopsy assays as a biomarker for detecting disease relapse or progression at the point of radiological progression. Data from this pilot study will help to design a future validation study for establishing optimal liquid biopsy for surveillance in advanced melanoma patients.

Detailed description: This prospective study will measure ctDNA in a simple plasma sample and using a dried blood spot assay, collected at the time of radiological disease progression. We will investigate the use of tumour informed and tumour naïve approaches, assessing targeted sequencing, copy number variations using whole genome low depth sequencing, fragmentomics and methylation as potential methods to improve molecular recurrence detection. We will also collect urine samples to investigate the use of cfDNA to detect relapse in the brain, which has been noted to be more challenging to detect using ctDNA in the blood than other sites of relapse.

In addition, we will investigate the use of novel immunophenotyping technology through a collaboration with MelioHealth (IMU) in the same setting. The IMU platform combines high resolution cellular analysis and machine learning to enable high-content, high-throughput and real-time cellular immunophenotyping from less than 2ml of whole blood. We hypothesize that disease relapse following immunotherapy may detectably trigger a patient's immune system memory, which may be particularly important for those patients who do not shed ctDNA.

Eligibility criteria: Inclusion Criteria:

* Histologically proven melanoma
* Unresectable stage III or stage IV disease, with confirmed radiological disease progression within 1 month of recruitment
* Patient has received at least 1 cycle of immunotherapy with checkpoint inhibitors for melanoma
* Undergoing standard of care active treatment with regular interval imaging or routine imaging surveillance following treatment completion/cessation
* Age over 16
* Not previously diagnosed with HIV, Hepatitis B or C (does not need testing)

Exclusion Criteria:

* Not on routine surveillance with interval imaging per standard of care
* Unable to provide informed consent due to psychological, medical or cognitive conditions.
* Unable to comply with schedule of study samples to be collected. Concurrent active malignancies needing treatment

Primary outcomes:
measure: Proportion of patients with measurable ctDNA at the point of radiological disease progression
timeFrame: 1 year
Secondary outcomes:
measure: Patient acceptance of liquid biopsy measured by proportion of enrolled patients to those invited to participate in the study
timeFrame: 1 year
measure: Cost of standard imaging pathway and additional cost of using liquid biopsy testing
timeFrame: 1 year
measure: Proportion of patients with positive tests in the different liquid biopsy assays to detect disease relapse
timeFrame: 1 year
Other outcomes:
Locations:
city: Chelsea
country: United Kingdom
facility: The Royal Marsden
state: London
Study officials:
References:
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