Ignite Creation Date:
2024-10-26 @ 3:38 PM
Last Modification Date:
2024-10-26 @ 3:38 PM
Study NCT ID:
NCT06566404
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-08-20
Brief Title:
Gene Expression Profiles and ctDNA for Risk Stratification in Patients With Melanoma
Sponsor:
None
Organization:
None
Study Overview
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
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
CORRESPOND
Brief 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
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 08 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 ie 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 ie 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
For patients with clinically node-negative cN0 disease sentinel lymph node biopsy SLNB is indicated for all patients with a melanoma of thickness of 08 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 ie 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 ie 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None