Improving Early Detection of Melanoma Recurrence With Circulating Tumor DNA (ctDNA)

Study Overview
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Brief Summary
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This is a non-randomized experimental biomarker study evaluating ctDNA levels in patients with stage IIB/C and stage IIIB/C/D melanoma skin cancer pre and post-surgery Study participants will complete a ctDNA test within 4 weeks of their planned surgical resection of their melanoma. Within 4 weeks post-surgery another ctDNA test will be completed. During these time points stool samples and diet questionnaires will be collected for biospecimen banking.

Detailed Description
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The investigators hypothesize that ctDNA levels drawn before and after surgical resection of a primary tumor and either sentinel lymph nodes or clinically involved metastatic lymph nodes will correlate with the presence of sentinel node microscopic metastatic disease and clinically evident nodal metastatic disease. The investigators also predict that approximately 20% of sentinel lymph node negative Stage IIB/IIC patients will have evidence of ctDNA positivity post-surgery. Primary Objective: To assess the feasibility of generating patient specific ctDNA assay from Signatera© test for primary melanoma samples submitted with clinical stage IIB/IIC and stage III melanoma patients. Secondary Objective(s): To investigate serum levels of melanoma ctDNA pre and postoperatively in clinical Stage IIB/C and Stage III melanoma patients. To evaluate the relationship of serum ctDNA levels pre-operatively with sentinel lymph node biopsy status in clinical Stage IIB/C patients. Evaluate for clearance or persistence of ctDNA levels post complete resection in patients with clinically evident lymph node metastasis (Stage IIIB/C/D). Assess feasibility of collection of pre- and post-operative stool samples

Official Title
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Improving Early Detection of Melanoma Recurrence With Circulating Tumor DNA (ctDNA)

Conditions
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Melanoma

Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: Patient must be ≥ 18 years of age. Patient must be a surgical candidate with Stage IIB, IIC melanoma or fully resectable Stage III B/C/D cutaneous melanoma. Patients with resectable in transit/nodal metastatic disease who have had prior adjuvant or systemic/intralesional therapy can be included provided that the planned resected lesions either progressed or developed while on or after completion of prior treatment. Patients with resectable in transit/nodal metastatic disease who are treated with neoadjuvant therapy prior to resection are also eligible provided that the initial blood and tumor biopsy sample are taken prior to initiation of neoadjuvant therapy. Tissue available meeting one of the following criteria: For patients with Clinical stage II primary tumors that have been biopsied prior to evaluation by the surgeon, or those with stage III tumors that have been partially/fully excised prior to definitive surgery, adequate tissue will be confirmed prior to enrollment to follow Natera's tissue sample collection instructions when selecting the appropriate specimen. OR For patients with bulky lymph nodes involved with clinically evident, biopsy proven metastatic disease, in transit metastasis, or with extensive residual primary tumor present prior to excision, and in the treating surgeon's assessment there will be extensive tumor for evaluation, the patient can be enrolled with tissue adequacy evaluation post resection Patient is willing to provide blood samples for Signatera testing as outlined in the study calendar. Patient is able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines. EXCLUSION CRITERIA: Patient is unable to provide informed consent or is unwilling to sign an approved consent form. Patient has other clinically significant disorders that would preclude safe study participation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum ctDNA acquisition, processing and results | The proportion of cases in which sample acquisition, processing and return of results from the two initial ctDNA (serum VAF allele levels, ng/ml) analyses occurs within 6 weeks of acquisition of the post-operative serum sample. The two ctDNA analyses are from the initial tumor biopsy and blood, and post-operative blood draw. | Within 4 weeks pre-surgery through a maximum of 4 weeks post-surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pre and Post-operative Serum Variant Allele Frequency | Pre-operative and post-operative serum Variant allele frequency (VAF) ng/ml from the Signatera© test in all evaluable patients | Within 4 weeks pre-surgery through a maximum of 4 weeks post-surgery | 
| Association of pre-operative and post-operative serum Variant allele frequency (VAF) levels (ng/ml) from the Signatera© test and sentinel lymph node biopsy metastatic status | Evaluate the relationship of serum Variant allele frequency (VAF) levels (ng/ml) pre-operatively with sentinel lymph node biopsy clinical outcome (positive/negative for metastatic disease) in clinical Stage IIB/C melanoma patients undergoing sentinel lymph node biopsy. | Within 4 weeks pre-surgery | 
| Pre-operative serum VAF levels (ng/mL) from Signatera© stratified by pre-operative sentinel lymph node and clinically evident lymph node metastatic status. | Evaluate association of pre-operative serum VAF levels (ng/ml) from Signatera© stratified by pre-operative sentinel lymph node eligible (Clinical stage IIB/IIC) patients vs. patients with clinically evident lymph node metastases (clinical stage III). | Within 4 weeks post-surgery | 
| Quantify the number of patients who develop detectable VAF levels (ng/ml) within the first 3 years after surgery and evaluate possible correlation with recurrence. | Proportion of participants with detectable VAF levels (ng/ml) using the Signatera© test at any time point during the surveillance period and any clinical or radiologic evidence of recurrence. | 3 years post resection of the last patient enrolled. | 
| Pre and Post-operative Stool Samples | Proportion of cases in which pre-operative and post-operative patient stool samples are successfully obtained | Within 4 weeks pre-surgery through a maximum of 4 weeks post-surgery | 
| The proportion of patients for which serum VAF levels (ng/ml) are undetectable post complete resection of either sentinel nodes or clinically evident lymph node metastases | The proportion of patients for which serum VAF levels (ng/ml) are undetectable post complete resection of either sentinel nodes or clinically evident lymph node metastases | Within 4 weeks post-surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stage II Melanoma, Stage III Melanoma, ctDNA, Circulating Tumor DNA, surgical resection, tumor marker, melanoma recurrence