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Utility of Plasma Circulating Tumor DNA (ctDNA) in Asymptomatic Subjects for the Detection of Neoplastic Disease (H1000)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02612350
Recruitment Status : Completed
First Posted : November 23, 2015
Last Update Posted : April 6, 2018
Information provided by (Responsible Party):
Pathway Genomics

Brief Summary:
Pathway Genomics Corporation (Pathway Genomics), a San Diego, California company, is involved in the development and validation of new molecular diagnostic assays for the analysis of circulating tumor deoxyribonucleic acid (DNA) (ctDNA) found in the plasma-derived DNA (cell-free DNA or cfDNA) in order to identify specific variants (mutations) in cancer driver genes. The purpose of testing for mutations in ctDNA is to detect and monitor cancer. All cells shed DNA into the bloodstream. Finding cancer-associated mutations in the cfDNA may lead to early detection of cancer in an otherwise apparently healthy (i.e. asymptomatic) individual or may allow the healthcare provider to more effectively monitor and treat a known cancer patient. The analysis is performed using a polymerase chain reaction (PCR)-based methodology where oligonucleotides are designed to target specific mutations in designated genes of interest followed by next generation deep sequencing of the amplified targets. Evaluation of the performance of these assays for screening for cancer in asymptomatic subjects is essential for the clinical validation of the use of these assays. The specific aim of this protocol is to obtain relevant human blood samples from individual subjects at higher than average risk for the development of cancer due to age, heredity, or environmental or toxic exposures for use in the statistical analysis of this method as an adjunct screening test for the potential presence of cancer.

Condition or disease Intervention/treatment
Mutation Neoplasms Genetic: ctDNA Analysis for the Detection of Genetic Mutations

Detailed Description:

The objectives of this study are to obtain human blood samples from asymptomatic subjects who have never been diagnosed with cancer, but who may be at increased risk for cancer due to heredity, exposures, age, or family history to assess the validity of screening healthy but at risk patients for cancer via analysis of ctDNA.

Specifically, the blood specimens will be collected from individuals who have responded to a self-administered health questionnaire that screens for higher risk of contracting cancer. Each participant will be asked to provide a 30 ml blood sample to be drawn by a primary care provider (PCP) or licensed phlebotomist. The specimens collected during the study may also be used in the research and development of new or modified molecular genetics assays. The results of these studies will be used to further the understanding of the use of ctDNA for the detection and monitoring of cancer in humans.

The blood samples are collected in blood collection tubes (BCT) called Cell-Free DNA BCT® manufactured by Streck and intended for collection, stabilization and transportation of cell-free plasma DNA. This device also stabilizes and preserves cellular genomic DNA present in nucleated blood cells and circulating epithelial cells (tumor cells) found in whole blood. This product has not been cleared by the U.S. Food and Drug Administration for In Vitro Diagnostic use and is labeled by Streck for research use only. Under the Clinical Laboratory Improvement Amendments (CLIA) regulations, laboratories are authorized to validate and use, as part of a laboratory-developed test (LDT), devices that have not been cleared or approved by the FDA. Pathway Genomics validated the CancerInterceptTM Detect molecular analysis system with the Streck tubes, in accordance with CLIA.

Once the specimen has been collected and sent to Pathway by the physician or the phlebotomist who collects the samples, all other processing and testing are conducted by Pathway laboratory personnel. The analysis begins with the separation of the plasma from the rest of the blood sample. cfDNA will then be isolated from each sample. The quantity of cfDNA is measured and then the sample is amplified via PCR for next generation sequencing. The results of the sequencing will then be analyzed for the presence of one or more of the 96 mutations analyzed in this assay. The data are then reviewed and a report will be generated.

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Study Type : Observational
Actual Enrollment : 1106 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Utility of Plasma Circulating Tumor DNA (ctDNA) in Asymptomatic Subjects for the Detection of Neoplastic Disease
Study Start Date : November 2015
Actual Primary Completion Date : August 2017
Actual Study Completion Date : August 2017

Resource links provided by the National Library of Medicine

Group/Cohort Intervention/treatment
Increased Risk for Cancer Development
The group is to include at least 1000 individuals who are at high risk for the development of cancer. Risk is assessed through the completion of a clinical history questionnaire. Examples of such subjects include those with known hereditary cancer syndrome pathogenic variants without a diagnosis of cancer, with significant family history of breast, ovarian, colon, or lung cancer or melanoma, or another strong history of cancer but no prior molecular diagnosis, heavy smokers or those exposed to carcinogens and mutagens. The individuals who meet criteria for inclusion will undergo cell-free DNA isolation and circulating-tumor DNA (ctDNA) analysis for the detection of genetic mutations associated with the possible development of a malignancy.
Genetic: ctDNA Analysis for the Detection of Genetic Mutations
Cell-free DNA (cfDNA) is isolated from a blood plasma sample and tested for the presence of 96 specific well-described mutations in 9 cancer driver genes. The presence of more than 2 copies of a mutation may indicate the presence of a malignancy. Follow up with the subject's physician would be needed for an examination and any additional testing that the physician wants to perform to further assess for the development of cancer.

Primary Outcome Measures :
  1. Number of subjects found with one or more of 96 ctDNA mutations [ Time Frame: 1 year ]
    A cohort of 1000 or more individuals who are at high risk for the development of cancer will be tested for the presence of 96 well-described mutations in 9 cancer driver genes via ctDNA analysis. The number of individuals with one or more of the 96 assayed mutations will be assessed.

  2. Number of copies of mutant alleles found in the positive subjects [ Time Frame: 1 year ]
    Among the cohort of subjects enrolled in the study in whom one or more of the 96 ctDNA mutations are detected, the number of copies per analyzed plasma sample will be calculated.

  3. Percentage of ctDNA found within the total amount of circulating free DNA (cfDNA) [ Time Frame: 1 year ]
    Within the samples found to contain one or more ctDNA mutation, the percentage of ctDNA within the total amount of cfDNA will be calculated.

Secondary Outcome Measures :
  1. Number of subjects with one or more of 96 ctDNA mutations who develop cancer [ Time Frame: 1 to 5 years ]
    The 1000 or more individuals in the study will be followed for 1 to 5 years to assess for the development of a malignancy. Special attention will be paid to the cohort who have initial assays indicating the presence of ctDNA. The subjects may be retested over time to show changing levels of ctDNA. Their own physicians will guide any follow up studies such as imaging or other laboratory testing. The test is designed as a means of case finding for cancer among individuals with high risk for development of cancer.

Biospecimen Retention:   Samples With DNA
Whole blood will be obtained, the plasma sample separated for the isolation of cell-free DNA, and the sample that may be stored will be excess plasma as well as potentially DNA from the buffy coat.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Individuals who are at increased risk for the development of cancer due to age over 50 years, a strong family history of cancer, known carrier of a pathogenic variant in a gene indicating an increased risk of cancer, for example a hereditary cancer syndrome, or due to exposure to environmental toxins, carcinogens, or mutagens, including tobacco. The individuals have to have the legal authority to provide consent, and therefore be 18 years of age or older.

Inclusion Criteria:

  • strong family history of cancer
  • known carrier of a pathogenic variant in a gene indicating an increased risk of cancer, for example, in the BRCA1 or TP53 genes.
  • exposure to environmental toxins, carcinogens, or mutagens, including but not limited to tobacco, radiation, asbestos, long-time industrial chemical exposure
  • age equal to or over 50 years

Exclusion Criteria:

  • prior diagnosis of cancer except basal cell carcinoma
  • no risk factors that place the individual at high risk
  • age under 18 years
  • individuals unwilling to sign the IRB-approved consent form

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02612350

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United States, California
Pathway Genomics
San Diego, California, United States, 92121
Sponsors and Collaborators
Pathway Genomics
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Principal Investigator: Glenn Braunstein, MD Pathway Genomics
Study Director: Anja Kammesheidt, PhD Pathway Genomics
Additional Information:
Bettegowda C, Sausen M, Leary RJ, Kinde I, Wang Y, Agrawal N, Bartlett BR, Wang H, Luber B, Alani RM, Antonarakis ES, Azad NS, Bardelli A, Brem H, Cameron JL, Lee CC, Fecher LA, Gallia GL, Gibbs P, Le D, Giuntoli RL, Goggins M, Hogarty MD, Holdhoff M, Hong SM, Jiao Y, Juhl HH, Kim JJ, Siravegna G, Laheru DA, Lauricella C, Lim M, Lipson EJ, Marie SK, Netto GJ, Oliner KS, Olivi A, Olsson L, Riggins GJ, Sartore-Bianchi A, Schmidt K, Shih lM, Oba-Shinjo SM, Siena S, Theodorescu D, Tie J, Harkins TT, Veronese S, Wang TL, Weingart JD, Wolfgang CL, Wood LD, Xing D, Hruban RH, Wu J, Allen PJ, Schmidt CM, Choti MA, Velculescu VE, Kinzler KW, Vogelstein B, Papadopoulos N, Diaz LA Jr. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med. 2014 Feb 19;6(224):224ra24. doi: 10.1126/scitranslmed.3007094.

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Responsible Party: Pathway Genomics Identifier: NCT02612350    
Other Study ID Numbers: Pathway Gennomics 004
First Posted: November 23, 2015    Key Record Dates
Last Update Posted: April 6, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Pathway Genomics:
high risk for developing cancer
Relative Risk
Early Detection of Cancer
Cancer Screening Tests
Cancer Screening
Additional relevant MeSH terms:
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