Cancer DNA Screening Pilot Study (CANDACE)

NCT02808884 | Completed DMC

• 1 other identifier: H16-00519
• Study Type: interventional
• Target: 1,514
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators have developed an assay that can sensitively and specifically detect DNA mutations circulating in human plasma that may be indicators of the presence of a solid tumor. This study is a pilot study to measure positive and negative predictive values of this assay as an indicator of the presence of a tumor in normal subjects

Conditions

Circulating Tumor Cells

Outcome Measures

Primary Outcomes (1)

• Measuring the positive and negative predictive value of a circulating tumor DNA blood test in detecting the presence of cancer or pre-cancerous lesions

  Within a year of all blood sample collections, the following will be determined: * Number of False Positive Tests - The number of participants with a confirmed positive blood test who participated in a diagnostic evaluation during which no cancer was found. * Number of True Positive Tests - The number of participants with a confirmed blood test who participated in a diagnostic evaluation during which a cancer was found.

  1-2 years

Secondary Outcomes (5)

• The enrollment rates for this study

  1-2 years

• The number of repeated versus sporadic positive test results within a year of the last blood draw.

  1-2 years

• The rate of participation in the medical imaging component of the study once a positive test result has been confirmed.

  1-2 years

• The number of medical imaging scans required per thousand individuals enrolled in the study.

  1-2 years

• The number of participants with abnormal medical imaging scans and of those cohorts, what fraction is cancer found.

  1-2 years

Study Arms (3)

Circulating tumor DNA assay- First test - Negative result

EXPERIMENTAL

Once the data is analyzed, participants with a negative result will be sent an email thanking them for their participation and informing them of the negative result.

Genetic: Circulating tumor DNA assay

Circulating tumor DNA assay - Second test- Negative result

EXPERIMENTAL

Participants whose sample provided a positive result after first test, will be contacted immediately by telephone by an oncologist co-investigator and concurrently sent a letter by mail informing them of the result and asking them to return for a second blood draw. We expect that this communication will happen with about a month of the original blood draw. The letter will include contact information for the study team and the oncologist co-investigators, in case the participant has any questions or concerns at this stage. A requisition form will be sent with the letter. Two 10mL tubes of blood will be drawn at the blood collection visit, to allow repeat testing and confirmation that the mutation is present consistently. Once the data is analyzed, participants with a negative result will be sent an email thanking them for their participation and informing them of the negative result.

Genetic: Circulating tumor DNA assay

Circulating tumor DNA assay - Second test- Positive result

EXPERIMENTAL

Participants with positive results after first test will be contacted by an oncologist and sent a letter informing them of the result. They will be ask to return for a second blood draw. The letter will include contact info of the study team and the oncologist co-investigators. A requisition form will be sent with the letter. Two 10mL tubes of blood will be drawn to allow repeat testing and confirmation that the mutation is consistently present. Participants whom additional blood sample yields a positive result for the same cancer mutations seen in the first blood draw, will be contacted by an oncologist to explain the results and next steps. This should happen within about a week of the second blood draw. Pending oncological evaluation of the participant and study results, a PET-CT scan with FDG agent, and possibly other tests will be requested. Unless exams suggest otherwise, the default follow-up will be a full body PET-CT.

Genetic: Circulating tumor DNA assay

Interventions

Circulating tumor DNA assay GENETIC

Blood samples will be separated into plasma and cellular fraction including erythrocytes and buffy coat.The plasma fraction will be placed in a separate tube and frozen for subsequent analysis. Frozen plasma samples, de-identified, will be delivered to Pathway Genomics where DNA content will be analyzed with a circulating tumor DNA assay employing the UBC/Boreal Genomics enrichment technology. All of the participants' plasma will be sent to Pathway, where it will be used up in the assay. Circulating tumor DNA assay results (raw sequencing data) from Pathway Genomics will be returned to UBC and analyzed for the presence of cancer mutations. Any samples showing activating mutations above the assay's technical Limit of Detection (LOD) will be called positive. One exception will be made for TP53 mutations that are known to exist in some normal individuals at low levels. For these mutations, a level of 0.1% will be set, above which the sample will be called positive.

Circulating tumor DNA assay - Second test- Negative result; Circulating tumor DNA assay - Second test- Positive result; Circulating tumor DNA assay- First test - Negative result

Eligibility Criteria

• Age: 55 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have never been diagnosed with cancer (except for non-melanoma skin cancer)
• Must be able to read and understand a consent form in English
• Be willing to consent to the required blood draws, medical exam and PET-CT scans
• Be willing to consent to any medical data related to this test, the imaging scans, and related follow up, being shared with the study investigators for the following year
• Be in good health and able to donate three tubes of blood
• Must have email
• Must be able to have blood work in the greater Vancouver area

You may not qualify if:

• Immunocompromised individuals
• Contra-indications to MRI or PET-CT
• Individuals with bleeding disorders

Sponsors & Collaborators

• British Columbia Cancer Agency: lead
• University of British Columbia: collaborator
• University of Utah: collaborator
• Pathway Genomics: collaborator
• Boreal Genomics: collaborator

Study Sites (1)

BC Cancer Agency- Vancouver Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Related Publications (7)

• Forbes SA, Bindal N, Bamford S, Cole C, Kok CY, Beare D, Jia M, Shepherd R, Leung K, Menzies A, Teague JW, Campbell PJ, Stratton MR, Futreal PA. COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer. Nucleic Acids Res. 2011 Jan;39(Database issue):D945-50. doi: 10.1093/nar/gkq929. Epub 2010 Oct 15.

  PMID: 20952405 BACKGROUND

• Cancer Genome Atlas Research Network; Weinstein JN, Collisson EA, Mills GB, Shaw KR, Ozenberger BA, Ellrott K, Shmulevich I, Sander C, Stuart JM. The Cancer Genome Atlas Pan-Cancer analysis project. Nat Genet. 2013 Oct;45(10):1113-20. doi: 10.1038/ng.2764.

  PMID: 24071849 BACKGROUND

• Punnoose EA, Atwal S, Liu W, Raja R, Fine BM, Hughes BG, Hicks RJ, Hampton GM, Amler LC, Pirzkall A, Lackner MR. Evaluation of circulating tumor cells and circulating tumor DNA in non-small cell lung cancer: association with clinical endpoints in a phase II clinical trial of pertuzumab and erlotinib. Clin Cancer Res. 2012 Apr 15;18(8):2391-401. doi: 10.1158/1078-0432.CCR-11-3148. Epub 2012 Apr 5.

  PMID: 22492982 BACKGROUND

• Spindler KL, Pallisgaard N, Vogelius I, Jakobsen A. Quantitative cell-free DNA, KRAS, and BRAF mutations in plasma from patients with metastatic colorectal cancer during treatment with cetuximab and irinotecan. Clin Cancer Res. 2012 Feb 15;18(4):1177-85. doi: 10.1158/1078-0432.CCR-11-0564. Epub 2012 Jan 6.

  PMID: 22228631 BACKGROUND

• Misale S, Yaeger R, Hobor S, Scala E, Janakiraman M, Liska D, Valtorta E, Schiavo R, Buscarino M, Siravegna G, Bencardino K, Cercek A, Chen CT, Veronese S, Zanon C, Sartore-Bianchi A, Gambacorta M, Gallicchio M, Vakiani E, Boscaro V, Medico E, Weiser M, Siena S, Di Nicolantonio F, Solit D, Bardelli A. Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer. Nature. 2012 Jun 28;486(7404):532-6. doi: 10.1038/nature11156.

  PMID: 22722830 BACKGROUND

• Kidess E, Heirich K, Wiggin M, Vysotskaia V, Visser BC, Marziali A, Wiedenmann B, Norton JA, Lee M, Jeffrey SS, Poultsides GA. Mutation profiling of tumor DNA from plasma and tumor tissue of colorectal cancer patients with a novel, high-sensitivity multiplexed mutation detection platform. Oncotarget. 2015 Feb 10;6(4):2549-61. doi: 10.18632/oncotarget.3041.

  PMID: 25575824 BACKGROUND

• 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.

  PMID: 24553385 BACKGROUND

MeSH Terms

Conditions

Neoplastic Cells, Circulating

Condition Hierarchy (Ancestors)

Neoplasm Metastasis; Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Alan M Nichol, MD

  British Columbia Cancer Agency

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Blood test screening for all who wish to participant. Additional screening test for those who test positive twice.

Study Record Dates

• First Submitted: June 7, 2016
• First Posted: June 22, 2016
• Study Start: September 19, 2016
• Primary Completion: June 10, 2019
• Study Completion: June 10, 2019
• Last Updated: August 24, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)