MelanomaCORRESPONDNCT06566404
Gene Expression Profiles and ctDNA for Risk Stratification in Patients With Melanoma
An observational study of Melanoma, run by European Institute of Oncology.
Trial summary
This study aims at assessing the role of MerlinTM and ctDNA in predicting the nodal status in patients with >pT3b melanoma, therefore candidate for adjuvant therapy regardless of sentinel lymph node status. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Melanoma
- How many people
- 200 participants
- Where
- No sites listed yet
- Study dates
- 30 Oct 2024to 1 Jan 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: CORRESPOND is a prospective, longitudinal, observational, non-interventional, translational clinical study enrolling patients with non-metastatic node-negative melanoma.
Who may be able to join
- male or female, aged at least 18 years;
- histologically documented melanoma;
- thickness > 2 mm (>pT3b);
- clinical node-negative (cN0) and non-metastatic (cM0) disease at ultrasound (US) and computed tomography (CT) or positron emission tomography (PET) scan;
- known BRAF, N-ras proto-oncogene (NRAS) and tyrosine-protein kinase (c-KIT) mutational status;
- candidate to SLNB;
- consent for the provision of plasma samples for ctDNA analysis and tissue samples (at a central laboratory).
Who cannot join
- SLNB performed;
- receipt of neoadjuvant therapy.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Gene Expression Profiles and ctDNA for Risk Stratification in Patients With Melanoma Eligible for Lymph Node Sentinel Biopsy (CORRESPOND): an Observational Prospective Study.
This study aims at assessing the role of MerlinTM and ctDNA in predicting the nodal status in patients with >pT3b melanoma, therefore candidate for adjuvant therapy regardless of sentinel lymph node status.
Read the detailed description
Cutaneous melanoma is a malignancy arising from melanocytes of the skin. Incidence rates are rising, particularly in White populations.
For patients with clinically node-negative (cN0) disease, sentinel lymph node biopsy (SLNB) is indicated for all patients with a melanoma of thickness of 0.8 mm or more (>pT1b) to stratify the prognosis and guarantee access to systemic adjuvant treatments.
Indeed, adjuvant immune checkpoint inhibitors or anti-proto-oncogene B-Raf (anti- BRAF) / Mitogen-activated protein kinase kinase (MEK) targeted agents were first demonstrated to improve clinical outcomes in patients with nodal involvement (stage III melanoma). Subsequently, immune-checkpoint inhibitors demonstrated a benefit in terms of disease-free survival also in patients with stage IIB and IIC melanoma, i.e., with melanoma of thickness of 2 mm or more (>pT3b). As a consequence, in this subgroup of patients, SLNB has lost its therapeutical implications and maintains only a role for prognostication, i.e., in the distinction between stages IIB-IIC (SLNB-negative; 71% of cases) and stage III (SLNB-positive; 29% of cases).
However, SLNB can be complicated by seroma, bleeding, wound infection, nerve damage, and even low rates of lymph edema have been reported. Moreover, depending on the country and healthcare system, it is a costly procedure for patients and society. According to an idea of professor Umberto Veronesi, Gentilini et al. demonstrated that the omission of SLNB in patients with cT1N0M0 breast cancer has not an impact on distant disease-free survival at 5 years (SOUND trial). Novel prognostic biomarkers for melanoma can substitute the SLNB role in prognostication and eventually lead to SLNB de-escalation.
Gene expression profiles (GEPs) and circulating tumor DNA (ctDNA) represents promising methods to assess tumor burden and tumor invasiveness, thus stratifying the prognosis.
ctDNA demonstrated to predict recurrence in patients with resected stage II-III melanoma, with a sensitivity and a specificity of 11-80% and 55-100%, according to the method (tumor-informed vs. tumor-naive), the techniques (digital droplet PRC [ddPCR] or others), the approach (single time point vs. dynamic assessment). In patients with non-resected stage II-III melanoma, the ctDNA-positivity rate is 35-37%. However, no data about pre-operative ctDNA as a predictor of SLNB status is available.
GEPs, alone or combined with clinicopathological features (CP-GEP), demonstrated to predict outcomes in patients with non-metastatic melanoma. In particular, MerlinTM assay is a CP-GEP model, developed by logistic regression modeling, which combines clinicopathologic factors (age and Breslow thickness) with the gene expression profiling component of 8 specific genes involved in cancer metastasis and melanosome biogenesis. It identifies patients at high or low risk of nodal metastasis. However, most patients included in studies validating this assay had a pathologic tumore stage 1-2 (pT1-2) melanoma; in patients with pathologic tumore stage 3 (pT3) melanoma this assay is characterized by high sensitivity but low specificity, and a negative predictive value of 75%.
The combination of CP-GEP and ctDNA may improve the prognostication and the prediction of SLNB status in patients with a >pT3b melanoma (candidate to adjuvant therapy regardless of nodal status), eventually leading to the de-escalation of SLNB. Indeed, in this population, in case of concordance between biomarker-positivity and SLNB status, SLNB can be definitively omitted, without missing any information.
- Conditions
- Melanoma
- Keywords
- Melanoma, MerlinTM, ctDNA, sentinel lymph node status
- Medical subject headings
- Melanoma
What is being measured
The primary outcome is the main question the study is designed to answer.
Model Performance
to compare the performance of the clinicopathologic model and the clinicopathologic model including ctDNA and MerlinTM in predicting SLNB-positivity in terms of area under receiver operating characteristic curve (AUC)
Measured: 36 months
Secondary outcomes (2)
the estimation of the correlation between ctDNA-positivity and SLNB-positivity
to assess the role of ctDNA-detected mutations in predicting the SLNB status
Measured: 36 months
The estimation of the correlation between MerlinTM/ctDNA-positivity and SLNB-positivity
To assess the role of MerlinTM and ctDNA in predicting micro- or macro- SLNB involvement (micrometastasis [TNM pathologic stage N1a (pN1a) or N2a (pN2a)] vs. macrometastasis [TNM pathologic stage N1b (pN1b) or N2b (pN2b]).
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2024
- Study start30 Oct 2024 (estimated)
- Primary completion1 Jul 2027 (estimated)
- Study completion1 Jan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for MelanomaStudies of the same condition, open and under way.
- More trials run by European Institute of OncologyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- European Institute of Oncology
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Elisabetta Pennacchioli, MD, Principal investigator, Istituto Europeo di Oncologia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06566404
- Sponsor's protocol ID
- L2-095
- Acronym
- CORRESPOND
- Status last verified
- Jun 2024
- First submitted
- 20 Aug 2024
- Last updated
- 23 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Long GV, Swetter SM, Menzies AM, Gershenwald JE, Scolyer RA. Cutaneous melanoma. Lancet. 2023 Aug 5;402(10400):485-502. doi: 10.1016/S0140-6736(23)00821-8. Epub 2023 Jul 24.
PubMed 37499671Gentilini OD, Botteri E, Sangalli C, Galimberti V, Porpiglia M, Agresti R, Luini A, Viale G, Cassano E, Peradze N, Toesca A, Massari G, Sacchini V, Munzone E, Leonardi MC, Cattadori F, Di Micco R, Esposito E, Sgarella A, Cattaneo S, Busani M, Dessena M, Bianchi A, Cretella E, Ripoll Orts F, Mueller M, Tinterri C, Chahuan Manzur BJ, Benedetto C, Veronesi P; SOUND Trial Group. Sentinel Lymph Node Biopsy vs No Axillary Surgery in Patients With Small Breast Cancer and Negative Results on Ultrasonography of Axillary Lymph Nodes: The SOUND Randomized Clinical Trial. JAMA Oncol. 2023 Nov 1;9(11):1557-1564. doi: 10.1001/jamaoncol.2023.3759.
PubMed 37733364Eroglu 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.
PubMed 36869646Bellomo D, Arias-Mejias SM, Ramana C, Heim JB, Quattrocchi E, Sominidi-Damodaran S, Bridges AG, Lehman JS, Hieken TJ, Jakub JW, Pittelkow MR, DiCaudo DJ, Pockaj BA, Sluzevich JC, Cappel MA, Bagaria SP, Perniciaro C, Tjien-Fooh FJ, van Vliet MH, Dwarkasing J, Meves A. Model Combining Tumor Molecular and Clinicopathologic Risk Factors Predicts Sentinel Lymph Node Metastasis in Primary Cutaneous Melanoma. JCO Precis Oncol. 2020;4:319-334. doi: 10.1200/po.19.00206. Epub 2020 Apr 14.
PubMed 32405608Mulder EEAP, Dwarkasing JT, Tempel D, van der Spek A, Bosman L, Verver D, Mooyaart AL, van der Veldt AAM, Verhoef C, Nijsten TEC, Grunhagen DJ, Hollestein LM. Validation of a clinicopathological and gene expression profile model for sentinel lymph node metastasis in primary cutaneous melanoma. Br J Dermatol. 2021 May;184(5):944-951. doi: 10.1111/bjd.19499. Epub 2020 Nov 2.
PubMed 32844403Lee RJ, Gremel G, Marshall A, Myers KA, Fisher N, Dunn JA, Dhomen N, Corrie PG, Middleton MR, Lorigan P, Marais R. Circulating tumor DNA predicts survival in patients with resected high-risk stage II/III melanoma. Ann Oncol. 2018 Feb 1;29(2):490-496. doi: 10.1093/annonc/mdx717.
PubMed 29112704Tie J, Cohen JD, Lahouel K, Lo SN, Wang Y, Kosmider S, Wong R, Shapiro J, Lee M, Harris S, Khattak A, Burge M, Harris M, Lynam J, Nott L, Day F, Hayes T, McLachlan SA, Lee B, Ptak J, Silliman N, Dobbyn L, Popoli M, Hruban R, Lennon AM, Papadopoulos N, Kinzler KW, Vogelstein B, Tomasetti C, Gibbs P; DYNAMIC Investigators. Circulating Tumor DNA Analysis Guiding Adjuvant Therapy in Stage II Colon Cancer. N Engl J Med. 2022 Jun 16;386(24):2261-2272. doi: 10.1056/NEJMoa2200075. Epub 2022 Jun 4.
PubMed 35657320
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Gene Expression Profiles and ctDNA for Risk Stratification in Patients With Melanoma Eligible for Lymph Node Sentinel Biopsy (CORRESPOND): an Observational Prospective Study.
- ClinicalTrials.gov ID
- NCT06566404
- Acronym / sponsor ID
- CORRESPOND / L2-095
- Conditions
- Melanoma
- Keywords
- Melanoma, MerlinTM, ctDNA, sentinel lymph node status
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- European Institute of OncologyUniversity, hospital or other
- Study start
- 30 Oct 2024 (estimated)
- Primary completion
- 1 Jul 2027 (estimated)
- Study completion
- 1 Jan 2028 (estimated)
- First posted
- 22 Aug 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study aims at assessing the role of MerlinTM and ctDNA in predicting the nodal status in patients with >pT3b melanoma, therefore candidate for adjuvant therapy regardless of sentinel lymph node status.
Detailed description
Cutaneous melanoma is a malignancy arising from melanocytes of the skin. Incidence rates are rising, particularly in White populations.
For patients with clinically node-negative (cN0) disease, sentinel lymph node biopsy (SLNB) is indicated for all patients with a melanoma of thickness of 0.8 mm or more (>pT1b) to stratify the prognosis and guarantee access to systemic adjuvant treatments.
Indeed, adjuvant immune checkpoint inhibitors or anti-proto-oncogene B-Raf (anti- BRAF) / Mitogen-activated protein kinase kinase (MEK) targeted agents were first demonstrated to improve clinical outcomes in patients with nodal involvement (stage III melanoma). Subsequently, immune-checkpoint inhibitors demonstrated a benefit in terms of disease-free survival also in patients with stage IIB and IIC melanoma, i.e., with melanoma of thickness of 2 mm or more (>pT3b). As a consequence, in this subgroup of patients, SLNB has lost its therapeutical implications and maintains only a role for prognostication, i.e., in the distinction between stages IIB-IIC (SLNB-negative; 71% of cases) and stage III (SLNB-positive; 29% of cases).
However, SLNB can be complicated by seroma, bleeding, wound infection, nerve damage, and even low rates of lymph edema have been reported. Moreover, depending on the country and healthcare system, it is a costly procedure for patients and society. According to an idea of professor Umberto Veronesi, Gentilini et al. demonstrated that the omission of SLNB in patients with cT1N0M0 breast cancer has not an impact on distant disease-free survival at 5 years (SOUND trial). Novel prognostic biomarkers for melanoma can substitute the SLNB role in prognostication and eventually lead to SLNB de-escalation.
Gene expression profiles (GEPs) and circulating tumor DNA (ctDNA) represents promising methods to assess tumor burden and tumor invasiveness, thus stratifying the prognosis.
ctDNA demonstrated to predict recurrence in patients with resected stage II-III melanoma, with a sensitivity and a specificity of 11-80% and 55-100%, according to the method (tumor-informed vs. tumor-naive), the techniques (digital droplet PRC [ddPCR] or others), the approach (single time point vs. dynamic assessment). In patients with non-resected stage II-III melanoma, the ctDNA-positivity rate is 35-37%. However, no data about pre-operative ctDNA as a predictor of SLNB status is available.
GEPs, alone or combined with clinicopathological features (CP-GEP), demonstrated to predict outcomes in patients with non-metastatic melanoma. In particular, MerlinTM assay is a CP-GEP model, developed by logistic regression modeling, which combines clinicopathologic factors (age and Breslow thickness) with the gene expression profiling component of 8 specific genes involved in cancer metastasis and melanosome biogenesis. It identifies patients at high or low risk of nodal metastasis. However, most patients included in studies validating this assay had a pathologic tumore stage 1-2 (pT1-2) melanoma; in patients with pathologic tumore stage 3 (pT3) melanoma this assay is characterized by high sensitivity but low specificity, and a negative predictive value of 75%.
The combination of CP-GEP and ctDNA may improve the prognostication and the prediction of SLNB status in patients with a >pT3b melanoma (candidate to adjuvant therapy regardless of nodal status), eventually leading to the de-escalation of SLNB. Indeed, in this population, in case of concordance between biomarker-positivity and SLNB status, SLNB can be definitively omitted, without missing any information.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- CORRESPOND is a prospective, longitudinal, observational, non-interventional, translational clinical study enrolling patients with non-metastatic node-negative melanoma.
Key inclusion criteria (7 listed)
- male or female, aged at least 18 years;
- histologically documented melanoma;
- thickness > 2 mm (>pT3b);
- clinical node-negative (cN0) and non-metastatic (cM0) disease at ultrasound (US) and computed tomography (CT) or positron emission tomography (PET) scan;
- known BRAF, N-ras proto-oncogene (NRAS) and tyrosine-protein kinase (c-KIT) mutational status;
Key exclusion criteria (2 listed)
- SLNB performed;
- receipt of neoadjuvant therapy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Model Performance
Time frame: 36 months
to compare the performance of the clinicopathologic model and the clinicopathologic model including ctDNA and MerlinTM in predicting SLNB-positivity in terms of area under receiver operating characteristic curve (AUC)
2 secondary outcomes
the estimation of the correlation between ctDNA-positivity and SLNB-positivity
Time frame: 36 months
The estimation of the correlation between MerlinTM/ctDNA-positivity and SLNB-positivity
Time frame: 36 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2024.
- Background: PubMed 37499671Long GV, Swetter SM, Menzies AM, Gershenwald JE, Scolyer RA. Cutaneous melanoma. Lancet. 2023 Aug 5;402(10400):485-502. doi: 10.1016/S0140-6736(23)00821-8. Epub 2023 Jul 24.
- Background: PubMed 37733364Gentilini OD, Botteri E, Sangalli C, Galimberti V, Porpiglia M, Agresti R, Luini A, Viale G, Cassano E, Peradze N, Toesca A, Massari G, Sacchini V, Munzone E, Leonardi MC, Cattadori F, Di Micco R, Esposito E, Sgarella A, Cattaneo S, Busani M, Dessena M, Bianchi A, Cretella E, Ripoll Orts F, Mueller M, Tinterri C, Chahuan Manzur BJ, Benedetto C, Veronesi P; SOUND Trial Group. Sentinel Lymph Node Biopsy vs No Axillary Surgery in Patients With Small Breast Cancer and Negative Results on Ultrasonography of Axillary Lymph Nodes: The SOUND Randomized Clinical Trial. JAMA Oncol. 2023 Nov 1;9(11):1557-1564. doi: 10.1001/jamaoncol.2023.3759.
- Background: PubMed 36869646Eroglu 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.
- Background: PubMed 32405608Bellomo D, Arias-Mejias SM, Ramana C, Heim JB, Quattrocchi E, Sominidi-Damodaran S, Bridges AG, Lehman JS, Hieken TJ, Jakub JW, Pittelkow MR, DiCaudo DJ, Pockaj BA, Sluzevich JC, Cappel MA, Bagaria SP, Perniciaro C, Tjien-Fooh FJ, van Vliet MH, Dwarkasing J, Meves A. Model Combining Tumor Molecular and Clinicopathologic Risk Factors Predicts Sentinel Lymph Node Metastasis in Primary Cutaneous Melanoma. JCO Precis Oncol. 2020;4:319-334. doi: 10.1200/po.19.00206. Epub 2020 Apr 14.
- Background: PubMed 32844403Mulder EEAP, Dwarkasing JT, Tempel D, van der Spek A, Bosman L, Verver D, Mooyaart AL, van der Veldt AAM, Verhoef C, Nijsten TEC, Grunhagen DJ, Hollestein LM. Validation of a clinicopathological and gene expression profile model for sentinel lymph node metastasis in primary cutaneous melanoma. Br J Dermatol. 2021 May;184(5):944-951. doi: 10.1111/bjd.19499. Epub 2020 Nov 2.
- Background: PubMed 29112704Lee RJ, Gremel G, Marshall A, Myers KA, Fisher N, Dunn JA, Dhomen N, Corrie PG, Middleton MR, Lorigan P, Marais R. Circulating tumor DNA predicts survival in patients with resected high-risk stage II/III melanoma. Ann Oncol. 2018 Feb 1;29(2):490-496. doi: 10.1093/annonc/mdx717.
- Background: PubMed 35657320Tie J, Cohen JD, Lahouel K, Lo SN, Wang Y, Kosmider S, Wong R, Shapiro J, Lee M, Harris S, Khattak A, Burge M, Harris M, Lynam J, Nott L, Day F, Hayes T, McLachlan SA, Lee B, Ptak J, Silliman N, Dobbyn L, Popoli M, Hruban R, Lennon AM, Papadopoulos N, Kinzler KW, Vogelstein B, Tomasetti C, Gibbs P; DYNAMIC Investigators. Circulating Tumor DNA Analysis Guiding Adjuvant Therapy in Stage II Colon Cancer. N Engl J Med. 2022 Jun 16;386(24):2261-2272. doi: 10.1056/NEJMoa2200075. Epub 2022 Jun 4.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Elisabetta Pennacchioli, MD principal investigator
Istituto Europeo di Oncologia
Questions about this trial
What is this clinical trial studying?
An observational study of Melanoma, run by European Institute of Oncology.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 23 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Elisabetta Pennacchioli, MD (0257489485, elisabetta.pennacchioli@ieo.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Model Performance (time frame: 36 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06566404, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2024.