Clinical trial NCT04825834: DNA Evaluation of Fragments for Early Interception - Lung Cancer Training Study (DELFI-L101 Study)
Official title: DNA Evaluation of Fragments for Early Interception - Lung Cancer Training Study (DELFI-L101 Study)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Lung Cancer
Head and Neck Cancer
Esophageal Cancer
Bladder Cancer
Kidney Cancer
Stomach Cancer
Colorectal Cancer
Pancreas Cancer
Liver Cancer
Skin Cancer
Lead sponsor: Delfi Diagnostics Inc.
Sponsor class: INDUSTRY
First posted: 2021-04-01
Enrollment: 2660
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Individuals ≥ 50 years of age who are eligible for lung cancer screening from medical, surgical, sub- specialty clinics, lung cancer screening, lung nodule, thoracic surgery, and chest clinic practices.

Brief summary: The primary objective of this study, DELFI-L101, is to train and test classifiers for lung cancer detection using the DELFI assay and other biomarker and clinical features.

Detailed description: Subjects will be enrolled into the DELFI-L101 study after informed consent and eligibility is confirmed. At enrollment, subjects will have blood specimens collected (\~40 mL) and 12 months post-enrollment their medical records will be reviewed.

Eligibility criteria: Inclusion Criteria:

All Participants:

1. Ability to understand and provide written informed consent
2. Age ≥ 50 years
3. Current or Former Smoker
4. ≥ 20 pack-years (pack years = number of packs per day X number of years smoked)

   Inclusion Group 1: High Risk Patients that meet criteria 5 and 6 below:
5. Prior thoracic imaging with computed tomography (CT) within 12 months of enrollment (CT imaging for lung cancer screening for participants meeting inclusion criteria 6a and 6b; or CT imaging for lung cancer screening or diagnostic CT for participants meeting inclusion criteria 6c)

   OR Planned thoracic imaging (CT) as part of standard of care within 6 weeks of enrollment (CT imaging for lung cancer screening for participants meeting inclusion criteria 6a and 6b; or CT imaging for lung cancer screening or diagnostic CT for participants meeting inclusion criteria 6c)

   AND
6. Meet one of the criteria below:

   1. No suspected or confirmed lung cancer diagnosis OR
   2. Suspected of lung cancer OR
   3. Confirmed, untreated lung cancer

   Inclusion Group 2: High Risk Patients that meet the following criteria:
7. Pathologic confirmed, invasive non-lung cancer diagnosis, originating from the esophagus (upper), colon or rectum, pancreas, stomach (including lower esophagus), head and neck, skin (excluding cutaneous basal cell and squamous cell carcinoma) kidney, or liver, with no prior systemic therapy, definitive therapy, radiation, or surgical resection.

OR Clinically confirmed invasive non-lung cancer diagnosis originating from the pancreas, kidney, or liver, based on imaging and clinical judgment with planned treatment and no prior systemic therapy, definitive therapy, radiation, or surgical resection.

OR Clinically (based on imaging and clinical judgment) or pathologically confirmed non-invasive or invasive bladder cancer with planned treatment and no prior systemic therapy, definitive therapy, radiation or surgical resection.

Exclusion Criteria:

All Participants:

1. Prior systemic therapy, definitive therapy, radiation, or surgical resection for cancer within one year prior to enrollment (with the exception of organ biopsies or surgery for non-melanoma skin cancer)
2. Any history of hematologic malignancies or myelodysplasia
3. Any history of organ tissue transplantation
4. Any history of blood product transfusion
5. Current pregnancy
6. Any condition that in the opinion of the Investigator should preclude the participant's participation in the study
7. Prior systemic therapy, definitive therapy, radiation, or surgical resection for the enrollment cancer diagnosis (with the exception of organ biopsies or surgery for non-melanoma skin cancer are not exclusionary)
8. Enrollment in any DELFI sponsored study

Primary outcomes:
measure: Accuracy of lung cancer detection measured by sensitivity, specificity, and the AUC of the ROC.
timeFrame: Approximately 12 months
Secondary outcomes:
measure: Accuracy (sensitivity and specificity) in clinical subgroups of interest
timeFrame: Approximately 12 months
measure: Prevalence-based measures, including positive predictive value (PPV), negative predictive value (NPV), and number needed to screen (NNS)
timeFrame: Approximately 12 months
measure: Accuracy of tumor of origin (confusion matrix of predicted versus actual cancer type)
timeFrame: Approximately 12 months
measure: Adverse events (AEs) associated with the blood specimen collection
timeFrame: Point in time of blood specimen collection (1day) at enrollment
measure: Expected distribution of the DELFI score in the intended use population and clinical subgroups of interest
timeFrame: Approximately 12 months
measure: Association of genomic features with clinical subgroups of interest
timeFrame: Approximately 12 months
measure: Analytical performance (e.g. repeatability/reproducibility)
timeFrame: Approximately 12 months
measure: Accuracy of multi-cancer detection measured by sensitivity, specificity, and the AUC of the ROC and tissue of origin (TOO) accuracy
timeFrame: Approximately 12 months
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
Study officials:
affiliation: The Cleveland Clinic
name: Peter Mazzone, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Memorial Sloan Kettering Cancer Center
name: Luke RG Pike, MD, DPhil
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mazzone PJ, Bach PB, Carey J, Schonewolf CA, Bognar K, Ahluwalia MS, Cruz-Correa M, Gierada D, Kotagiri S, Lloyd K, Maldonado F, Ortendahl JD, Sequist LV, Silvestri GA, Tanner N, Thompson JC, Vachani A, Wong KK, Zaidi AH, Catallini J, Gershman A, Lumbard K, Millberg LK, Nawrocki J, Portwood C, Rangnekar A, Sheridan CC, Trivedi N, Wu T, Zong Y, Cotton L, Ryan A, Cisar C, Leal A, Dracopoli N, Scharpf RB, Velculescu VE, Pike LRG. Clinical Validation of a Cell-Free DNA Fragmentome Assay for Augmentation of Lung Cancer Early Detection. Cancer Discov. 2024 Nov 1;14(11):2224-2242. doi: 10.1158/2159-8290.CD-24-0519.