Utility of Plasma Circulating Tumor DNA (ctDNA) in Asymptomatic Subjects for the Detection of Neoplastic Disease (H1000)
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|ClinicalTrials.gov Identifier: NCT02612350|
Recruitment Status : Completed
First Posted : November 23, 2015
Last Update Posted : April 6, 2018
|Condition or disease||Intervention/treatment|
|Mutation Neoplasms||Genetic: ctDNA Analysis for the Detection of Genetic Mutations|
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.
|Study Type :||Observational|
|Actual Enrollment :||1106 participants|
|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|
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.
- 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.
- 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.
- 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.
- 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
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 ClinicalTrials.gov identifier (NCT number): NCT02612350
|United States, California|
|San Diego, California, United States, 92121|
|Principal Investigator:||Glenn Braunstein, MD||Pathway Genomics|
|Study Director:||Anja Kammesheidt, PhD||Pathway Genomics|