Clinical trial NCT02889978: The Circulating Cell-free Genome Atlas Study
Official title: The Circulating Cell-free Genome Atlas Study
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Neoplasms
Cancer
Keywords: Cancer Screening
High-Throughput Nucleotide Sequencing
Deep Sequencing
Circulating cell-free tumor DNA
Lead sponsor: GRAIL, Inc.
Sponsor class: INDUSTRY
First posted: 2016-09-07
Enrollment: 15254
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

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

Primary outcomes:
measure: 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.
timeFrame: 30 months
measure: To develop and evaluate models for discriminating cancer versus non-cancer and tissue of origin.
timeFrame: 30 months
measure: To evaluate concordance of variants identified in sequencing of tumor tissue and cfNA sequencing results in plasma from the same subject.
timeFrame: 30 months
Secondary outcomes:
measure: 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.
timeFrame: Year 1, 2, 3, 4, 5
measure: 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.
timeFrame: Year 1, 2, 3, 4, 5
Other outcomes:
Locations:
city: Daphne
country: United States
facility: Southern Cancer Center, PC - Daphne
state: Alabama
city: Mobile
country: United States
facility: Southern Cancer Center, P.C. - Mobile Infirmary
state: Alabama
city: Mobile
country: United States
facility: Southern Cancer Center, PC - Mobile Airport
state: Alabama
city: Mobile
country: United States
facility: Southern Cancer Center, PC - Springhill Medical Center
state: Alabama
city: Phoenix
country: United States
facility: Mayo Clinic - Arizona
state: Arizona
city: Fort Smith
country: United States
facility: Mercy Fort Smith
state: Arkansas
city: Santa Barbara
country: United States
facility: Sansum Clinic - 540
state: California
city: Santa Barbara
country: United States
facility: Sansum Clinic- 317
state: California
city: Solvang
country: United States
facility: Sansum Clinic - Viborg
state: California
city: Aurora
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Boulder
country: United States
facility: Rocky Mountain Cancer Center
state: Colorado
city: Centennial
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Colorado Springs
country: United States
facility: Rocky Mountain Cancer Center
state: Colorado
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Englewood
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Lakewood
country: United States
facility: Rocky Mountain Cancer Center
state: Colorado
city: Littleton
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Lone Tree
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Longmont
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Pueblo
country: United States
facility: Rocky Mountain Cancer Center
state: Colorado
city: Thornton
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Hartford
country: United States
facility: Hartford HealthCare Cancer Institute at Hartford Hospital
state: Connecticut
city: New Britain
country: United States
facility: Hartford New Britain
state: Connecticut
city: Coral Gables
country: United States
facility: UMHC Lennar Foundation - Coral Gables
state: Florida
city: Coral Springs
country: United States
facility: UMHC Sylvester- Coral Springs
state: Florida
city: Deerfield Beach
country: United States
facility: University of Miami Sylvester at Deerfield Beach
state: Florida
city: Hollywood
country: United States
facility: University of Miami Sylvester at Hollywood
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic - Florida
state: Florida
city: Kendall
country: United States
facility: University of Miami Sylvester at Kendall
state: Florida
city: Miami
country: United States
facility: University of Miami Sylvester Comprehensive Cancer Center
state: Florida
city: Ocala
country: United States
facility: Florida Cancer Affiliates - Ocala
state: Florida
city: Pensacola
country: United States
facility: Woodlands Medical Specialists, PA
state: Florida
city: Plantation
country: United States
facility: University of Miami Sylvester at Plantation
state: Florida
city: Arlington Heights
country: United States
facility: Illinois Cancer Specialists
state: Illinois
city: Niles
country: United States
facility: Illinois Cancer Specialists
state: Illinois
city: Lexington
country: United States
facility: Baptist Health Lexington
state: Kentucky
city: Louisville
country: United States
facility: Baptist Health Louisville
state: Kentucky
city: Paducah
country: United States
facility: Baptist Health Paducah
state: Kentucky
city: Bethesda
country: United States
facility: Maryland Oncology Hematology, P.A.
state: Maryland
city: Brandywine
country: United States
facility: Maryland Oncology Hematology, P.A.
state: Maryland
city: Clinton
country: United States
facility: Maryland Oncology Hematology, P.A.
state: Maryland
city: Columbia
country: United States
facility: Maryland Oncology Hematology, P.A.
state: Maryland
city: Rockville
country: United States
facility: Maryland Oncology Hematology, P.A.
state: Maryland
city: Silver Spring
country: United States
facility: Maryland Oncology Hematology, P.A.
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Burlington
country: United States
facility: Lahey Hospital & Medical Center
state: Massachusetts
city: Peabody
country: United States
facility: Lahey Hospital & Medical Center - Peabody
state: Massachusetts
city: Coon Rapids
country: United States
facility: Minnesota Oncology Hematology, P.A. - Main
state: Minnesota
city: Edina
country: United States
facility: Minnesota Oncology Hematology, P.A. - Edina
state: Minnesota
city: Minneapolis
country: United States
facility: Minnesota Oncology Hematology, P.A. - Woodbury
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Minnesota
city: Woodbury
country: United States
facility: Minnesota Oncology Hematology, P.A. - Coon Rapids
state: Minnesota
city: Joplin
country: United States
facility: Mercy Joplin
state: Missouri
city: Springfield
country: United States
facility: Mercy Research - Springfield
state: Missouri
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering - Basking Ridge
state: New Jersey
city: Middletown
country: United States
facility: Memorial Sloan Kettering, NY - Monmouth
state: New Jersey
city: Albany
country: United States
facility: New York Oncology Hematology, P.C.
state: New York
city: Albany
country: United States
facility: New York Oncology Hematology, P.C.
state: New York
city: Binghamton
country: United States
facility: Broome Oncology, LLC
state: New York
city: Clifton Park
country: United States
facility: New York Oncology Hematology, P.C.
state: New York
city: Johnson City
country: United States
facility: Broome Oncology, LLC
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering - Rockville Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering, NY - Commack
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering, NY - West Harrison
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering
state: New York
city: Cincinnati
country: United States
facility: Oncology Hematology Care, Inc. - Reading Road
state: Ohio
city: Cincinnati
country: United States
facility: Oncology Hematology Care, Inc. - Fairfield
state: Ohio
city: Cincinnati
country: United States
facility: Christ Hospital Health Network - The Lindner Center Cancer Research Division
state: Ohio
city: Cincinnati
country: United States
facility: Oncology Hematology Care, Inc. - Mercy Health
state: Ohio
city: Cincinnati
country: United States
facility: Oncology Hematology Care, Inc. - E. Galbraith
state: Ohio
city: Cincinnati
country: United States
facility: Oncology Hematology Care, Inc. - Malsbary
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Fairfield
country: United States
facility: Oncology Hematology Care, Inc. - Five Mile Road
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University Knight Cancer Institute
state: Oregon
city: Portland
country: United States
facility: Northwest Cancer Specialists, P.C. dba Compass Oncology
state: Oregon
city: Portland
country: United States
facility: Northwest Cancer Specialists, P.C. dba Compass Oncology
state: Oregon
city: Portland
country: United States
facility: Northwest Cancer Specialists, P.C. dba Compass Oncology
state: Oregon
city: Tualatin
country: United States
facility: Northwest Cancer Specialists, P.C. dba Compass Oncology
state: Oregon
city: Allentown
country: United States
facility: Lehigh Valley Hospital - Cedar Crest
state: Pennsylvania
city: Bethlehem
country: United States
facility: Cancer Center at Lehigh Valley Hospital - Muhlenberg
state: Pennsylvania
city: Greenville
country: United States
facility: Bon Secours Saint Francis Cancer Center
state: South Carolina
city: Seneca
country: United States
facility: Prisma Health - Upstate
state: South Carolina
city: Spartanburg
country: United States
facility: Spartanburg Regional Healthcare System
state: South Carolina
city: Sioux Falls
country: United States
facility: Avera Research Institute
state: South Dakota
city: Chattanooga
country: United States
facility: Tennessee Oncology Medical Park II
state: Tennessee
city: Chattanooga
country: United States
facility: Tennessee Oncology Memorial Plaza
state: Tennessee
city: Cleveland
country: United States
facility: Tennessee Oncology Cleveland Clinic
state: Tennessee
city: Crossville
country: United States
facility: Tennessee Oncology CMC
state: Tennessee
city: Dickson
country: United States
facility: Tennessee Oncology Dickson
state: Tennessee
city: Franklin
country: United States
facility: Tennessee Oncology Franklin
state: Tennessee
city: Gallatin
country: United States
facility: Tennessee Oncology Gallatin
state: Tennessee
city: Hermitage
country: United States
facility: Tennessee Oncology Summit
state: Tennessee
city: Lebanon
country: United States
facility: Tennessee Oncology Lebanon
state: Tennessee
city: Murfreesboro
country: United States
facility: Tennessee Oncology Murfreesboro
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology Midtown
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology Nashville
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology SCCBC
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology St. Thomas West
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology Skyline
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology Southern Hills
state: Tennessee
city: Shelbyville
country: United States
facility: Tennessee Oncology Shelbyville
state: Tennessee
city: Smyrna
country: United States
facility: Tennessee Oncology Stonecrest
state: Tennessee
city: Amarillo
country: United States
facility: Texas Oncology - West Texas
state: Texas
city: Bedford
country: United States
facility: Texas Oncology-Bedford
state: Texas
city: Dallas
country: United States
facility: TXO - Methodist Dallas Cancer Center
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Dallas Forest Ln
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Presbyterian Cancer Center Dallas
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Baylor Charles A. Sammons Cancer Center
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology-Fort Worth
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology-Southwest Fort Worth
state: Texas
city: Grapevine
country: United States
facility: Texas Oncology - Grapevine
state: Texas
city: Harlingen
country: United States
facility: Texas Oncology Cancer Care and Research Center - Harlingen
state: Texas
city: Longview
country: United States
facility: Texas Oncology - Longview Cancer Center
state: Texas
city: McAllen
country: United States
facility: Texas Oncology - McAllen
state: Texas
city: Mesquite
country: United States
facility: Texas Oncology - Mesquite
state: Texas
city: New Braunfels
country: United States
facility: Texas Oncology-New Braunfels
state: Texas
city: Plano
country: United States
facility: Texas Oncology - Plano East
state: Texas
city: Plano
country: United States
facility: Texas Oncology - Plano West
state: Texas
city: Rockwall
country: United States
facility: Texas Oncology - Rockwall
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology-San Antonio Downtown
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology - San Antonio Northeast
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology-San Antonio Medical Center
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology-San Antonio Stone Oak
state: Texas
city: Sherman
country: United States
facility: Texas Oncology - Sherman
state: Texas
city: The Woodlands
country: United States
facility: Texas Oncology-The Woodlands
state: Texas
city: Tyler
country: United States
facility: Texas Oncology - Tyler
state: Texas
city: Weslaco
country: United States
facility: Texas Oncology - Weslaco
state: Texas
city: Wichita Falls
country: United States
facility: Texas Oncology - West Texas
state: Texas
city: Alexandria
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Arlington
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Gainesville
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Leesburg
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Woodbridge
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Seattle
country: United States
facility: Benaroya Research Institute at Virginia Mason
state: Washington
city: Vancouver
country: United States
facility: Northwest Cancer Specialists, P.C. dba Compass Oncology
state: Washington
city: Yakima
country: United States
facility: Yakima Valley Memorial Hospital/North Star Lodge
state: Washington
city: Toronto
country: Canada
facility: UHN Princess Margaret Cancer Centre
state: Ontario
Study officials:
affiliation: GRAIL, Inc.
name: Eric Fung, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Shao SH, Allen B, Clement J, Chung G, Gao J, Hubbell E, Liu MC, Swanton C, Tang WHW, Yimer H, Tummala M. Multi-cancer early detection test sensitivity for cancers with and without current population-level screening options. Tumori. 2023 Jun;109(3):335-341. doi: 10.1177/03008916221133136. Epub 2022 Oct 31.
citation: 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.
citation: 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.
citation: 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.
citation: 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.