SPARC - Screening for Lung Cancer With Platelets Via an AI-enabled RNA-based Classifier

Overview

The purpose of this study is to test whether combining a unique analytical approach with changes in platelet RNA expression accurately diagnoses lung cancer. Using retrospective platelet transcriptomic data from 522 patients with non-small cell lung cancer (NSCLC, the most common type of lung cancer), an approach that appears to accurately classify lung cancer has been developed. The study will build upon these retrospective analyses to prospectively recruit patients with newly diagnosed lung cancer, obtain platelet RNA samples from whole blood, and perform validation analyses. This research will also test whether this approach accurately distinguishes benign from malignant lung nodules.

Interventions

• Diagnostic test Platelet RNA-based assay
  Up to 20mL (the maximum blood volume collected) of whole blood will be collected by peripheral venipuncture by a site phlebotomist into sterile, 4mL EDTA-containing venipuncture tubes. The minimum whole blood collected will be 4mL.

Primary outcome measures

• Sensitivity [Time frame: up to one day after study enrollment]
• Specificity [Time frame: up to one day after study enrollment]
• Positive predictive value (PPV) [Time frame: up to one day after study enrollment]
• Negative Predictive Value (NPV) [Time frame: up to one day after study enrollment]

Secondary outcome measures (3)

• Performance Across Lung Cancer Stage [Time frame: up to one day after study enrollment]
• Performance Across Lung Cancer Histologic Subtypes [Time frame: up to one day after study enrollment]
• Validation Completion [Time frame: up to one day after study enrollment]

Eligibility criteria

Study Population 1: Treatment-Naïve Patients with a Lung Nodule or Lung Cancer

Inclusion criteria

• Aged 21 years or older
• Meeting at least one of the following two criteria:
• Diagnosed with any stage or type of lung cancer
• Having at least one lung nodule identified on imaging (e.g., low dose computed tomography \[LDCT\] or other diagnostic chest imaging) that was completed within 180 days prior to enrollment, and where there is planned or recommended biopsy, surgical resection, radiation therapy, systemic therapy, or other invasive diagnostic or therapeutic procedure to further evaluate the nodule(s) in the next six months based on the clinical judgment of the patient's provider(s)

Exclusion criteria

• Other diagnosis of, or treatment for, any cancer within the last 6 months except for non-melanoma skin cancer, carcinoma in situ of the cervix, or low-grade prostate cancer (defined as Gleason score ≤ 6) treated locally
• A history of lung cancer or metastatic cancer to the lungs from an extrathoracic primary site with definitive treatment (surgical, medical, or radiotherapy) within the past 2 years
• Currently receiving any systemic therapy (chemotherapy, immunotherapy, and/or targeted therapy) or radiation therapy for lung cancer
• Already undergone surgical resection of the lung cancer in part or in whole
• Have undergone invasive diagnostic or therapeutic procedures (e.g., biopsy, surgery) related to the lung nodule within the past 3 months
• Unable to provide blood sample

Study Population 2: Control Subjects

Inclusion criteria

• Aged 21 years or older

Exclusion criteria

• Any active malignancy or diagnosis of cancer within the last 6 months except for non-melanoma skin cancer, carcinoma in situ of the cervix, or low-grade prostate cancer (defined as Gleason score ≤ 6) treated locally
• Treatment for any cancer within the last 6 months except for non-melanoma skin cancer, carcinoma in situ of the cervix, or low-grade prostate cancer (defined as Gleason score ≤ 6) treated locally
• Hospitalization or surgery (other than minor surgery such as mole removal) within the last 8 weeks
• Renal failure (defined as eGFR < 60 mL/min/1.73m² or on dialysis)
• Liver failure (defined as having hepatic encephalopathy of any degree, OR moderately severe coagulopathy defined as INR ≥ 1.5, OR known cirrhosis, OR ALT of ≥ 10X ULN, OR total bilirubin of ≥ 3.0 mg/dL, OR diagnosis of liver failure)
• Decompensated or end-stage heart failure (defined as ACC/AHA Stage C or Stage D heart failure)
• Venous thrombosis, myocardial infarction, or stroke within the last 8 weeks
• Currently pregnant or have been pregnant within the last 12 weeks
• Any blood product transfusion within the last 8 weeks
• Personal history of lung cancer at any time
• Unable to provide blood sample

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Observational model

Case-control

Study locations

United States · 2 centers

• University of Utah — Salt Lake City
• Veterans Affairs SLC Health Care System (VAMC) — Salt Lake City

Publications

• National Lung Screening Trial Research Team; Aberle DR, Adams AM, Berg CD, Black WC, Clapp JD, Fagerstrom RM, Gareen IF, Gatsonis C, Marcus PM, Sicks JD. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011 Aug 4;365(5):395-409. doi: 10.1056/NEJMoa1102873. Epub 2011 Jun 29. PMID 21714641
• Kurzrock R, Chaudhuri AA, Feller-Kopman D, Florez N, Gorden J, Wistuba II. Healthcare disparities, screening, and molecular testing in the changing landscape of non-small cell lung cancer in the United States: a review. Cancer Metastasis Rev. 2024 Dec;43(4):1217-1231. doi: 10.1007/s10555-024-10187-6. Epub 2024 May 16. PMID 38750337
• Henderson LM, Benefield T, Bosemani T, Long JM, Rivera MP. Impact of the COVID-19 Pandemic on Volumes and Disparities in Lung Cancer Screening. Chest. 2021 Jul;160(1):379-382. doi: 10.1016/j.chest.2020.12.033. Epub 2021 Jan 5. No abstract available. PMID 33417898
• Kalinke L, Thakrar R, Janes SM. The promises and challenges of early non-small cell lung cancer detection: patient perceptions, low-dose CT screening, bronchoscopy and biomarkers. Mol Oncol. 2021 Oct;15(10):2544-2564. doi: 10.1002/1878-0261.12864. Epub 2020 Dec 14. PMID 33252175
• Bach PB, Jett JR, Pastorino U, Tockman MS, Swensen SJ, Begg CB. Computed tomography screening and lung cancer outcomes. JAMA. 2007 Mar 7;297(9):953-61. doi: 10.1001/jama.297.9.953. PMID 17341709
• Croswell JM, Baker SG, Marcus PM, Clapp JD, Kramer BS. Cumulative incidence of false-positive test results in lung cancer screening: a randomized trial. Ann Intern Med. 2010 Apr 20;152(8):505-12, W176-80. doi: 10.7326/0003-4819-152-8-201004200-00007. PMID 20404381
• Brenner DJ. Radiation risks potentially associated with low-dose CT screening of adult smokers for lung cancer. Radiology. 2004 May;231(2):440-5. doi: 10.1148/radiol.2312030880. PMID 15128988
• Best MG, Vancura A, Wurdinger T. Platelet RNA as a circulating biomarker trove for cancer diagnostics. J Thromb Haemost. 2017 Jul;15(7):1295-1306. doi: 10.1111/jth.13720. PMID 28671345

Identifiers

NCT: NCT07460440 · 193163 · LC240423

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗