The Circulating Cell-free Genome Atlas Study

Study Overview
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Brief Summary
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GRAIL is using deep sequencing of circulating cell-free nucleic acids (cfNAs) to develop assays to detect cancer early in blood. The purpose of this study is to collect biological samples from participants with a new diagnosis of cancer (blood and tumor tissue) and from participants who do not have a diagnosis of cancer (blood) in order to characterize the population heterogeneity in cancer and non-cancer participants and to develop models for distinguishing cancer from non-cancer.

Detailed Description
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This is a prospective, multi-center, observational study with collection of de-identified biospecimens and clinical data from at least 15,000 participants from clinical networks in the United States and Canada. The study will enroll approximately 10,500 cancer participants (CANCER arm) and approximately 4,500 representative participants without a clinical diagnosis of cancer (NON-CANCER arm). Clinical information, demographics, and medical data relevant to cancer status are collected from all participants and their medical record at baseline (time of biospecimen collection), and subsequently from the medical record at intermittent future time points, at least annually for up to 5 years.

Official Title
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The Circulating Cell-free Genome Atlas Study

Conditions
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Neoplasms, Cancer

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for Non-Cancer Arm Participants: Age 20 years or older Able to provide a written informed consent Exclusion Criteria for Non-Cancer Arm Participants: Known current or prior diagnosis of cancer except non-melanoma skin cancer Oral or IV corticosteroid use in past 14 days prior to blood draw Pregnancy (by self-report) Current febrile illness Acute exacerbation or flare of an inflammatory condition requiring escalation in medical therapy within 14 days prior to blood draw. Recipient of organ transplant or prior non-autologous (allogeneic) bone marrow or stem cell transplant Poor health status or unfit to tolerate blood draw Inclusion Criteria for Cancer Arm Participants: Age 20 years or older Able to provide a written informed consent Have either of the following: A. Confirmed cancer diagnosis (any stage I-IV, as well as carcinoma in situ (CIS) within 90 days prior to or up to 42 days after study blood draw, based upon assessment of a pathological specimen OR B. A high suspicion for a cancer diagnosis by clinical and/or radiological assessment, with planned biopsy or surgical resection to establish a definitive diagnosis within 6 weeks (42 days) after study blood draw Exclusion Criteria for Cancer Arm Participants: Known prior diagnosis of cancer except non-melanoma skin cancer Currently receiving, or ever received, any of the following therapies to treat their current cancer: surgical management of the cancer beyond that required to establish the cancer diagnosis; local, regional or systemic chemotherapy including chemoembolization; targeted therapy, immunotherapy including cancer vaccines; hormone therapy; or radiation therapy Pregnancy (by self-report) Current febrile illness Acute exacerbation or flare of an inflammatory condition requiring escalation in medical therapy within 14 days prior to blood draw. Recipient of organ transplant or prior non-autologous (allogeneic) bone marrow or stem cell transplant Poor health status or unfit to tolerate blood draw

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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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 |
| --- | --- |
| Cancer arm<br>Participants with new diagnosis of cancer (multiple tumor types) from which a blood sample and contemporaneous FFPE tumor tissue will be collected. | |
| Non-cancer arm<br>Participants with no known diagnosis or past history of cancer from which a blood sample will be collected. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To collect and study clinically-annotated biospecimens, specifically peripheral blood and contemporary tumor tissue when available, to characterize cfNA profiles from deep sequencing and to estimate the population heterogeneity in two arms of the study. |  | 30 months | 
| To develop and evaluate models for discriminating cancer versus non-cancer and tissue of origin. |  | 30 months | 
| To evaluate concordance of variants identified in sequencing of tumor tissue and cfNA sequencing results in plasma from the same subject. |  | 30 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To explore the relationship between genomic results and clinical outcomes based on collection of longitudinal information (at least annually for up to 5 years) from medical records for all consenting participants. |  | Year 1, 2, 3, 4, 5 | 
| To enable assessment of the performance of an analytically validated clinical laboratory version of the NGS assay (under development) to detect circulating tumor DNA (ctDNA) in plasma. |  | Year 1, 2, 3, 4, 5 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Circulating cell-free tumor DNA, Cancer Screening, High-Throughput Nucleotide Sequencing, Deep Sequencing