Power of Liquid Biopsy Tracking in Immunotherapy Treated Stage IV Melanoma

NCT ID: NCT06710093

Last Updated: 2024-11-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Total Enrollment

100 participants

Study Classification

OBSERVATIONAL

Study Start Date

2025-02-01

Study Completion Date

2029-01-01

Brief Summary

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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

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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.

Conditions

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Metastatic Melanoma

Keywords

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ctDNA testing advanced melanoma immune checkpoint inhibitors (ICI)

Study Design

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Observational Model Type

CASE_ONLY

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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Histologically proven melanoma

Unresectable stage III or stage IV disease, with confirmed radiological disease progression within 1 month of recruitment

No interventions assigned to this group

Eligibility Criteria

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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
Minimum Eligible Age

16 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Royal Marsden NHS Foundation Trust

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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The Royal Marsden

Chelsea, London, United Kingdom

Site Status

Countries

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United Kingdom

Central Contacts

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Arjun Modi, MSc

Role: CONTACT

Phone: 020 7352 8171

Email: [email protected]

Laura Boddy

Role: CONTACT

Phone: 020 7352 8171

Email: [email protected]

Facility Contacts

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Javi Pozas, MD

Role: primary

Laura Boddy

Role: backup

Kate Young, MD

Role: backup

References

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Pascual J, Attard G, Bidard FC, Curigliano G, De Mattos-Arruda L, Diehn M, Italiano A, Lindberg J, Merker JD, Montagut C, Normanno N, Pantel K, Pentheroudakis G, Popat S, Reis-Filho JS, Tie J, Seoane J, Tarazona N, Yoshino T, Turner NC. ESMO recommendations on the use of circulating tumour DNA assays for patients with cancer: a report from the ESMO Precision Medicine Working Group. Ann Oncol. 2022 Aug;33(8):750-768. doi: 10.1016/j.annonc.2022.05.520. Epub 2022 Jul 6.

Reference Type BACKGROUND
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Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Rutkowski P, Lao CD, Cowey CL, Schadendorf D, Wagstaff J, Dummer R, Ferrucci PF, Smylie M, Hogg D, Hill A, Marquez-Rodas I, Haanen J, Guidoboni M, Maio M, Schoffski P, Carlino MS, Lebbe C, McArthur G, Ascierto PA, Daniels GA, Long GV, Bastholt L, Rizzo JI, Balogh A, Moshyk A, Hodi FS, Wolchok JD. Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. N Engl J Med. 2019 Oct 17;381(16):1535-1546. doi: 10.1056/NEJMoa1910836. Epub 2019 Sep 28.

Reference Type BACKGROUND
PMID: 31562797 (View on PubMed)

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Reference Type BACKGROUND
PMID: 34571969 (View on PubMed)

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Reference Type BACKGROUND
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Reference Type BACKGROUND
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Reference Type BACKGROUND
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Reference Type BACKGROUND
PMID: 30137228 (View on PubMed)

Eroglu Z, Krinshpun S, Kalashnikova E, Sudhaman S, Ozturk Topcu T, Nichols M, Martin J, Bui KM, Palsuledesai CC, Malhotra M, Olshan P, Markowitz J, Khushalani NI, Tarhini AA, Messina JL, Aleshin A. Circulating tumor DNA-based molecular residual disease detection for treatment monitoring in advanced melanoma patients. Cancer. 2023 Jun 1;129(11):1723-1734. doi: 10.1002/cncr.34716. Epub 2023 Mar 4.

Reference Type BACKGROUND
PMID: 36869646 (View on PubMed)

Related Links

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https://www.nice.org.uk/guidance/ng14/chapter/Recommendations#follow-up-after-treatment-for-melanoma

Recommendations \| Melanoma: assessment and management \| Guidance \| NICE

Other Identifiers

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CCR6083

Identifier Type: -

Identifier Source: org_study_id