cfDNA Assay Prospective Observational Validation for Early Cancer Detection and Minimal Residual Disease

Study Overview
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Brief Summary
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This is an observational case-control study to train and validate a genome-wide methylome enrichment platform to detect multiple cancer types and to differentiate amongst cancer types. The cancers included in this study are brain, breast, bladder, cervical, colorectal, endometrial, esophageal, gastric, head and neck, hepatobiliary, leukemia, lung, lymphoma, multiple myeloma, ovarian, pancreatic, prostate, renal, sarcoma, and thyroid. These cancers were selected based on their prevalence and mortality to maximize impact on clinical care. Additionally, the ability of the whole-genome methylome enrichment platform to detect minimal residual disease after completion of cancer treatment and to detect relapse prior to clinical presentation will be evaluated in four cancer types (breast, colorectal, lung, prostate). These cancers were selected based on the existing clinical landscape and treatment availability.

Detailed Description
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This is an observational case-control study that includes individuals with cancer and individuals without known cancer. All participants will have clinical follow-up after enrollment. A subset of individuals with cancer will also have longitudinal blood sampling to evaluate the ability of the genome-wide methylome enrichment platform to detect minimal residual disease. This includes individuals with Stage I-III breast, colorectal, lung, or prostate cancer (Tier 1 Cancers). At baseline, all participants will provide a blood sample and applicable clinical data. Participants with a Tier 1 cancer will have clinical follow-up and blood draws after the completion of first-line treatment, every 3 months for the first year after first-line treatment, and every 6 months for an additional 2 years. All other cases will have clinical follow-up once a year for 3 years after enrollment. Control participants will have clinical follow-up every 6 months for up to 3 years from enrollment to evaluate cancer status. The blood test to be used in this study is a highly sensitive, epigenomic-based genome-wide methylome enrichment platform. The assay includes bisulfite-free, non-degradative genome-wide DNA methylation profiling from small quantities of cell-free DNA (cfDNA). Libraries constructed from cfDNA are enriched for methylated CpGs and preserve the native fragment length. This is followed by high throughput sequencing. For all assays, samples from participants with cancer and participants without cancer will be run together to reduce batch effects using methodology determined by the Sponsor. Results from the liquid biopsy test will not be returned to clinicians or participants.

Official Title
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cfDNA Assay Multicenter Prospective Observational Validation for Early Cancer Detection, Minimal Residual Disease, and Relapse

Conditions
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Brain Cancer, Breast Cancer, Bladder Cancer, Cervical Cancer, Colorectal Cancer, Endometrial Cancer, Esophageal Cancer, Stomach Cancer, Head and Neck Cancer, Hepatobiliary Cancer, Leukemia, Lung Cancer, Lymphoma, Multiple Myeloma, Ovarian Cancer, Pancreatic Cancer, Prostate Cancer, Renal Cancer, Sarcoma, Thyroid Cancer

Participation Criteria
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Eligibility Criteria
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Case Inclusion Criteria: Newly diagnosed (within 90 days) with cancer or a recurrence of a cancer diagnosed >5 years ago of one of the following subtypes: Invasive Brain, Breast, Bladder, Cervical, Colorectal, Endometrial, Esophageal, Gastric, Head and Neck, Hepatobiliary, Lung, Ovarian, Pancreatic, Prostate, Renal, Sarcoma, Thyroid; Leukemia, Lymphoma, Multiple Myeloma Able and willing to provide informed consent ≥40 years of age Case Exclusion Criteria: Currently receiving any treatment for cancer Currently taking any demethylating agents/DNA hypomethylating agents Simultaneously diagnosed with two or more invasive cancers Diagnosed with any invasive or non-invasive cancer in addition to the index cancer in the last 5 years Currently diagnosed with any chronic hematopoietic cancer (e.g. chronic CLL) in addition to the index cancer Currently diagnosed with any myelodysplastic syndromes and/or precursor hematologic conditions (e.g. MGUS) in addition to the index cancer Women who are known to be pregnant (self-reported) Control Inclusion Criteria Not diagnosed with any cancer in the last 5 years (non-invasive cancer is allowed) Able and willing to provide informed consent ≥40 years of age Control Exclusion Criteria Currently receiving any treatment for cancer Currently taking any demethylating agents/DNA hypomethylating agents Women who are known to be pregnant (self-reported)

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cases<br>Cases will include participants with newly diagnosed, treatment-naive cancer at the time of enrollment. | |
| Controls<br>Controls will include participants without known cancer at the time of enrollment. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detection of cancer | Differentiation of cancer signals from cases and non-cancer signals from controls based on analysis of cfDNA using the genome-wide methylome enrichment platform | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detection of specific cancer types | Differentiation of cancer signals from cases with a specific cancer type and non-cancer signals from controls based on analysis of cfDNA using the genome-wide methylome enrichment platform | 24 months | 
| Tissue of origin | Identification of the correct tissue of origin (as determined by clinical diagnosis) for cancer cases based on analysis of cfDNA using the genome-wide methylome enrichment platform | 18 months | 
| Clinical outcomes | Recurrence-free survival and overall survival among cancer cases | 54 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multi-cancer early detection, Liquid Biopsy, Methylome, Cancer screening, cell-free DNA