Liquid Biopsy for Lung Cancer

Overseen By Dan Raz, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: City of Hope Medical Center

Disqualifiers: Lung cancer symptoms, Recent cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 4 weeks

108 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to assess the practicality of using a liquid biopsy—a blood test that detects tiny bits of DNA from lung cancer cells—to screen individuals at high risk for lung cancer. If a liquid biopsy indicates cancer, individuals might be more inclined to undergo a low-dose CT scan to confirm the results. This approach could help detect lung cancer earlier, making it easier to treat. The trial seeks participants who have smoked heavily, quit within the last 15 years, and are willing to provide a blood sample and potentially undergo a CT scan. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could enhance early lung cancer detection.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.

What prior data suggests that this liquid biopsy is safe for lung cancer screening?

Research has shown that cell-free DNA liquid biopsies are generally safe for patients. In one study, the Galleri test, a type of liquid biopsy, accurately detected lung cancer, identifying it in most cases with a sensitivity of 78.4% and a specificity of 99.5%.

A liquid biopsy involves taking a blood sample to look for DNA from cancer cells. This method is easy on patients because it only requires a simple blood draw, unlike traditional biopsies that may need tissue samples from the body. Studies have not reported any major side effects, making it a low-risk option for patients.

Overall, cell-free DNA liquid biopsy is considered safe and does not involve significant adverse events. It is already used in some cases to check for cancer changes in people who cannot have a regular biopsy. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the liquid biopsy for lung cancer because it offers a non-invasive method to detect cancer using a simple blood test. Unlike traditional methods like tissue biopsies or low-dose CT scans (LDCT), which can be invasive or expose patients to radiation, liquid biopsies analyze cell-free DNA in the blood to identify cancer markers. This method can potentially detect cancer earlier and with less discomfort for patients. Additionally, liquid biopsies may provide quicker results and be repeated easily to monitor cancer progression or response to treatment.

What evidence suggests that this trial's methods could be effective for lung cancer screening?

Research has shown that liquid biopsies, which test for tiny amounts of cancer DNA in the blood, hold promise for detecting lung cancer. In this trial, participants in Cohort A will undergo a liquid biopsy, with the option for a low-dose CT scan (LDCT) if results are positive. Conversely, participants in Cohort B will undergo an LDCT, with the option for a liquid biopsy on the same day. A clinical study found that the Galleri test, a type of liquid biopsy, correctly identified lung cancer 78.4% of the time and non-cancer 99.5% of the time. Sensitivity measures how often the test detects cancer when present, while specificity measures how often it correctly identifies the absence of cancer. High specificity means few false alarms, making it a reliable tool. Unlike traditional biopsies, liquid biopsies are non-invasive and can detect genetic changes in cancers, aiding early diagnosis. Overall, this method could help catch lung cancer earlier, possibly leading to better outcomes. ^{1 2 3 6 7}

Who Is on the Research Team?

Dan Raz

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for English-speaking individuals aged 50-80 who are at high risk for lung cancer due to a smoking history of 20 or more pack-years and, if they've quit, it was within the last 15 years. They must consent to screening with liquid biopsy or CT scan and have insurance covering LDCT at specified centers. Excluded are those with any recent cancer diagnosis (except non-melanoma skin cancer) or symptoms of lung cancer.

Inclusion Criteria

Documented written informed consent of the participant.

Received referral for counseling for lung cancer screening and would qualify for LDCT.

Health Insurance that will pay for a LDCT for lung cancer screening at either City of Hope Duarte, Newport Beach (Newport Diagnostic Imaging), or Lancaster (Renaissance Imaging/Antelope Valley Outpatient Imaging Center).

Exclusion Criteria

Any cancer diagnosis within past 5 years, excluding non-melanoma skin cancer.

Chest CT scan or chest positron emission tomography (PET)/CT within 12 months.

You have signs of lung cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo either a liquid biopsy or low dose CT scan, with optional crossover based on results

4 weeks

1 visit (in-person or at home)

Follow-up

Participants are monitored for follow-through on screening and sociodemographic data collection

6 months

1 visit (in-person or virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Cell-Free DNA Liquid Biopsy
• Low Dose Computed Tomography of the Chest

Trial Overview

The study is testing the practicality of using cell-free DNA liquid biopsies for early detection of lung cancer in high-risk patients compared to low dose CT scans. It aims to see if positive results from liquid biopsies encourage patients to follow up with CT scans, potentially increasing early detection rates.

How Is the Trial Designed?

Group I: Cohort B (LDCT, optional liquid biopsy) Experimental Treatment 3 Interventions

Participants undergo low dose CT with optional liquid biopsy on the same day as LDCT.

Group II: Cohort A (liquid biopsy, optional LDCT) Experimental Treatment 3 Interventions

Participants undergo collection of blood sample (liquid biopsy), with option to undergo LDCT if liquid biopsy results are positive.

Cell-Free DNA Liquid Biopsy is already approved in United States, European Union for the following indications:

Approved in United States as Liquid Biopsy for:

• Non-small cell lung cancer screening in high-risk patients

Approved in European Union as Liquid Biopsy for:

• Non-small cell lung cancer screening in high-risk patients

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Circulating cell-free DNA (cfDNA) testing is a promising minimally invasive method for managing metastatic non-small-cell lung cancer (NSCLC), offering insights into tumor heterogeneity and allowing for repeated assessments over time.

cfDNA testing can be used for various applications, including early diagnosis, monitoring treatment response, and identifying predictive markers, highlighting its potential to enhance patient management in NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of circulating free DNA in the management of NSCLC. Esposito Abate, R., Pasquale, R., Fenizia, F., et al.[2019]

Cell-free DNA (cfDNA) analysis, or liquid biopsy, is a non-invasive method for diagnosing various cancers, making it a promising alternative to traditional invasive diagnostic techniques.

This review highlights the potential of cfDNA as a prognostic biomarker in cancers such as hepatocellular carcinoma, lung cancer, breast cancer, and hematologic malignancies, emphasizing its role in improving cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Investigation into Cell-Free DNA in Different Common Cancers. Nafar, S., Hosseini, K., Shokrgozar, N., et al.[2023]

Liquid biopsy, particularly through the analysis of cell-free DNA (cfDNA), is becoming a crucial tool in lung cancer diagnosis, allowing for real-time tumor characterization and detection of important genetic mutations.

cfDNA has already been integrated into clinical practice for identifying EGFR mutations in lung cancer, and advancements in technology are expanding its use for early detection and monitoring of minimal residual disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liquid biopsy tracking of lung tumor evolutions over time. Russo, A., De Miguel Perez, D., Gunasekaran, M., et al.[2020]

In a study of 10 treatment-naïve patients with metastatic non-small cell lung cancer (NSCLC), early analysis of cell-free DNA (cfDNA) provided quicker results compared to traditional tumor biopsy, with a median reporting time of 9 days for cfDNA versus 20 days for tumor biopsy.

Both cfDNA and tumor biopsy identified actionable biomarkers in four patients, demonstrating that cfDNA analysis can effectively complement tumor biopsy in guiding treatment decisions for NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Blood-based Liquid Biopsy in Patients with Treatment-naïve Metastatic Adenocarcinoma of the Lung: A Case Series. Peled, M., Bar, J., Avni, L., et al.[2022]

In a study of 35 patients with advanced lung adenocarcinoma treated with afatinib, the objective response rate was 77.1% and the median progression-free survival (PFS) was 13.8 months, indicating that afatinib is an effective treatment for this patient group.

Monitoring circulating cell-free DNA (cfDNA) using digital polymerase chain reaction (dPCR) can predict treatment efficacy, as patients with undetectable EGFR mutant alleles in cfDNA at 4 weeks had a longer median PFS (14.3 months) compared to those with detectable alleles (10.0 months).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monitoring of somatic mutations in circulating cell-free DNA by digital PCR and next-generation sequencing during afatinib treatment in patients with lung adenocarcinoma positive for EGFR activating mutations. Iwama, E., Sakai, K., Azuma, K., et al.[2022]

In a study of 143 patients with advanced non-small-cell lung cancer (NSCLC), circulating cell-free DNA (cfDNA) testing identified actionable mutations in 20% of samples at diagnosis, allowing for targeted therapy initiation in 10% of cases where tissue biopsies were not feasible.

cfDNA testing demonstrated a sensitivity of 67% and specificity of 89%, showing it can effectively guide treatment decisions and avoid invasive procedures, with a high response rate of 88% among patients who started targeted therapy based solely on cfDNA results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Non-Small-Cell Lung Cancer Based on Circulating Cell-Free DNA and Impact of Variation Allele Frequency. Bustamante Alvarez, JG., Janse, S., Owen, DH., et al.[2022]

Liquid biopsies, particularly through the analysis of cell-free DNA (cfDNA), provide a minimally invasive and sensitive method for managing lung cancer, which is crucial given its high mortality rate.

There is an urgent need for collaboration across various sectors to overcome challenges and accelerate the clinical implementation of liquid biopsies in lung cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Possible application of circulating free tumor DNA in non-small cell lung cancer patients. Karachaliou, N., Sosa, AE., Molina, MA., et al.[2020]

Next-generation sequencing (NGS) of circulating free DNA (cfDNA) from plasma samples in 107 patients with metastatic lung cancer showed that cfDNA can effectively detect clinically relevant mutations, with 26 out of 50 identified mutations found in cfDNA.

The sensitivity of cfDNA testing was 58% and specificity was 87%, indicating that while it is a promising tool for mutation screening, it may not detect all mutations present in tumor DNA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noninvasive diagnosis of actionable mutations by deep sequencing of circulating free DNA in lung cancer from never-smokers: a proof-of-concept study from BioCAST/IFCT-1002. Couraud, S., Vaca-Paniagua, F., Villar, S., et al.[2018]

Liquid biopsies, which analyze cell-free DNA from blood, offer a noninvasive way to monitor and treat pediatric cancers, providing insights at diagnosis and during treatment without the need for anesthesia or invasive procedures.

Despite challenges like limited blood volume and low mutation rates in childhood cancers, advancements in multiomic approaches and bioinformatics are enhancing the effectiveness and applicability of liquid biopsies in pediatric oncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liquid biopsies in pediatric oncology: opportunities and obstacles. Sundby, RT., Pan, A., Shern, JF.[2023]

Citations

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ctDNA is useful for detecting genetic aberrations in patients with metastatic solid tumors who cannot undergo biopsy, and it can also be used as ...

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12189613/

Clinical Utility of ctDNA Analysis in Lung Cancer—A Review

The high specificity of liquid biopsy, indicating low rates of false positive results, makes it a reliable tool for confirming mutations in NSCLC patients.

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These results provide preliminary evidence that liquid biopsies may improve VTE risk stratification in addition to clinical parameters.

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guidelines.carelonmedicalbenefitsmanagement.com

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Cell-free DNA Testing (Liquid Biopsy) for the Management of ...

Liquid (ctDNA) based testing is considered medically necessary for individuals with invasive malignancy for whom the liquid biopsy test is a companion ...