Next Generation pErsonalized tX(Therapy) With Plasma DNA Trial-2 in Refractory Solid Tumors (The NEXT-2 Trial)

Study Overview
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Brief Summary
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Analysis of cell free DNA(cfDNA), unlike tissue biopsy, presents a new tool for the monitoring and treatment of cancer. The investigators have developed a differentiated sequencing assay, Digital Sequencing Technology (DST) that enables detection of rare genomic abnormalities with ultra high-specificity and sensitivity. The investigators assay is able to eliminate the error and distortion created by sample-prep and sequencing processes in standard NGS(next-generation sequencing ) workflows and produce near-perfect representations of all rare variants. The investigators have shown that in sequencing a comprehensive cancer panel of 80kbp in 0.1% cancer cell line titration samples, standard Illumina SBS(sequencing by synthesis ) generates many high-quality false positive variant calls in the range of 0.05-5%, while the investigators assay resulted in highly sensitive and completely error-free variant calls across the entire panel. This work indicates the remarkable potential of using the investigators assay in deep analysis of cfDNA, thereby allowing researchers and clinicians to comprehensively and non-invasively monitor the genetic dimension of cancer throughout the body.

Detailed Description
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Same as above

Official Title
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Next Generation pErsonalized tX(Therapy) With Plasma DNA Trial-2 in Refractory Solid Tumors (The NEXT-2 Trial)

Conditions
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Metastatic Gastrointestinal Cancer, Genitourinary Cancer

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients older than 20 years Patients with histologically confirmed metastatic gastrointestinal cancer, rare cancer, lung cancer Patients with histologically confirmed metastatic cancer, who do not have sufficient biopsy material to undergo mutational testing of their tumor, or do not have feasible biopsy sites; melanoma/lung cancer and any solid tumor cancer types will be eligible for the study. Written informed consent form Exclusion Criteria: Concurrent disease or condition that would make the subject inappropriate for study participation or any serious medical condition that would interfere with the subject's safety. Double primary cancer (except for any cancer in remission for > 5 years, cervix cancer in situ, basal cell cancer in situ, any in situ cancers that are resected)

Ages Eligible for Study
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Minimum Age: 20 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| metastatic cancer<br>metastatic gastrointestinal cancer metastatic genitourinary cancer other rare cancer lung cancer | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| feasibility | The feasibility of the use of plasma cell free DNA - molecular profiling to direct targeted therapies in the treatment of refractory solid tumors -ANALYSIS : The analysis of this exploratory study will be primarily descriptive. Data will be presented by means of summary statistics tables, graphs and listings. | From date of start of targeted treatment oriented by NEXT until the date of first progression or date of death from any cause, whichever came first, assessed up to 1 year ] | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression free survival (PFS), | The progression free survival (PFS), duration of response and overall survival of patients with refractory solid tumors. | 1years | 
| molecular profile with cell-free DNA | To compare the correlation between primary/metastatic tumor formalin-fixed paraffin-embedded DNA molecular profile with cell-free DNA from plasma | From date of start of targeted treatment oriented by NEXT until the date of first progression or date of death from any cause, whichever came first, assessed up to 1 year ] | 
| serial cfDNA samples | To evaluate changes in the tumor's molecular profile on serial cfDNA samples when patients progress after an initial response to targeted treatment | From date of start of targeted treatment oriented by NEXT until the date of first progression or date of death from any cause, whichever came first, assessed up to 1 year ] | 
| Duration of response | The progression free survival (PFS), duration of response and overall survival of patients with refractory solid tumors. | 1years | 
| overall survival | The progression free survival (PFS), duration of response and overall survival of patients with refractory solid tumors. | 1years | 
| response rate | The response rate of molecular-profile directed treatments in refractory solid tumors | up to 1 year |