The Circulating Cell-free Genome Atlas Study (CCGA)

• ClinicalTrials.gov Identifier: NCT02889978
• Recruitment Status: Active, not recruiting
• First Posted: September 7, 2016
• Last Update Posted: August 3, 2022
• Sponsor: GRAIL, LLC
• Information provided by (Responsible Party): GRAIL, LLC

Tracking Information

• First Submitted Date: August 18, 2016
• First Posted Date: September 7, 2016
• Last Update Posted Date: August 3, 2022
• Actual Study Start Date: August 4, 2016
• Estimated Primary Completion Date: March 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 26, 2018)

• 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. [ Time Frame: 30 months ]
• To develop and evaluate models for discriminating cancer versus non-cancer and tissue of origin. [ Time Frame: 30 months ]
• To evaluate concordance of variants identified in sequencing of tumor tissue and cfNA sequencing results in plasma from the same subject. [ Time Frame: 30 months ]

Original Primary Outcome Measures (submitted: August 31, 2016)

Evidence of histologically confirmed cancer in subjects with circulating tumor DNA (ctDNA) detected by deep sequencing. [ Time Frame: 18 months ]

Clinically annotated plasma samples from cancer and non-cancer subjects will undergo deep sequencing to characterize cfNA profiles and to estimate the population heterogeneity in the two arms of the study.

Current Secondary Outcome Measures (submitted: September 26, 2018)

• 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. [ Time Frame: 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. [ Time Frame: Year 1, 2, 3, 4, 5 ]

Original Secondary Outcome Measures (submitted: August 31, 2016)

• Number of genomic variants detected in plasma cfNA in cancer subjects who also have available tumor tissue. [ Time Frame: 18 months ]
  Concordance of variants identified in sequencing plasma cfNA and tumor tissue from the same subject will be evaluated.
• Survival or clinical cancer status (none, mild, moderate, or severe) of all subjects with results from deep sequencing plasma cfNA. [ Time Frame: Year 1, 2, 3, 4, 5 ]
  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.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: The Circulating Cell-free Genome Atlas Study
• Official Title: The Circulating Cell-free Genome Atlas Study
• Brief Summary: 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: 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.
• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

Plasma, white blood cells, formalin fixed, paraffin embedded (FFPE) tumor tissue

• Sampling Method: Non-Probability Sample
• Study Population: Eligible study participants will be recruited from participating medical centers in a ratio of 3 non-cancer participants for every 7 cancer participants within each individual research center. Non-cancer subject recruitment will be monitored to achieve demographic characteristics (eg, age, gender, ethnicity, smoking status) reflective of those of the cancer participants.

Condition

• Neoplasms
• Cancer

• Intervention: Not Provided

Study Groups/Cohorts

• Cancer arm
  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
  Participants with no known diagnosis or past history of cancer from which a blood sample will be collected.

Publications *

• Shao SH, Allen B, Clement J, Chung G, Gao J, Hubbell E, Liu MC, Swanton C, Tang WW, Yimer H, Tummala M. Multi-cancer early detection test sensitivity for cancers with and without current population-level screening options. Tumori. 2022 Oct 31:3008916221133136. doi: 10.1177/03008916221133136. Online ahead of print.
• Bredno J, Lipson J, Venn O, Aravanis AM, Jamshidi A. Clinical correlates of circulating cell-free DNA tumor fraction. PLoS One. 2021 Aug 25;16(8):e0256436. doi: 10.1371/journal.pone.0256436. eCollection 2021.
• Klein EA, Richards D, Cohn A, Tummala M, Lapham R, Cosgrove D, Chung G, Clement J, Gao J, Hunkapiller N, Jamshidi A, Kurtzman KN, Seiden MV, Swanton C, Liu MC. Clinical validation of a targeted methylation-based multi-cancer early detection test using an independent validation set. Ann Oncol. 2021 Sep;32(9):1167-1177. doi: 10.1016/j.annonc.2021.05.806. Epub 2021 Jun 24.
• Larson MH, Pan W, Kim HJ, Mauntz RE, Stuart SM, Pimentel M, Zhou Y, Knudsgaard P, Demas V, Aravanis AM, Jamshidi A. A comprehensive characterization of the cell-free transcriptome reveals tissue- and subtype-specific biomarkers for cancer detection. Nat Commun. 2021 Apr 21;12(1):2357. doi: 10.1038/s41467-021-22444-1. Erratum In: Nat Commun. 2022 May 4;13(1):2553.
• Liu MC, Oxnard GR, Klein EA, Swanton C, Seiden MV; CCGA Consortium. Sensitive and specific multi-cancer detection and localization using methylation signatures in cell-free DNA. Ann Oncol. 2020 Jun;31(6):745-759. doi: 10.1016/j.annonc.2020.02.011. Epub 2020 Mar 30.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: May 5, 2020): 15254
• Original Estimated Enrollment (submitted: August 31, 2016): 10000
• Estimated Study Completion Date: March 2024
• Estimated Primary Completion Date: March 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, United States

Administrative Information

• NCT Number: NCT02889978
• Other Study ID Numbers: GRAIL-001
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: GRAIL, LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: GRAIL, LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Kathryn N Kurtzman, MD; GRAIL, LLC

• PRS Account: GRAIL, LLC
• Verification Date: August 2022