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

Trial Summary

What is the purpose of this trial?

This clinical trial investigates how practical and doable (feasibility) cell-free deoxyribonucleic acid (DNA) liquid biopsy is in screening high-risk patients for lung cancer. Currently, a low dose computed tomography (CT) scan is used to screen for lung cancer, however, due to various factors, few high-risk patients are screened. Liquid biopsy utilizes technology that can detect small amounts of DNA shed by cancer cells and may be able to spot lung cancer at an earlier stage. If a positive result comes back from the liquid biopsy, a patient may be more willing to get a low dose CT (LDCT) scan, possibly confirming the biopsy's findings and thus leading to more 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 data supports the effectiveness of the treatment Cell-Free DNA Liquid Biopsy for lung cancer?

Research shows that cell-free DNA (cfDNA) testing is a promising tool for managing non-small-cell lung cancer (NSCLC). It offers a minimally invasive way to detect mutations, monitor treatment response, and assess tumor changes over time, which can help guide therapy decisions and avoid more invasive procedures. ^{1 2 3 4 5}

Is liquid biopsy safe for humans?

Liquid biopsy, which includes cell-free DNA (cfDNA) testing, is considered safe because it is minimally invasive, involving only a blood test rather than a traditional tissue biopsy. ^{2 3 4 6 7}

How is the Cell-Free DNA Liquid Biopsy treatment different from other lung cancer treatments?

The Cell-Free DNA Liquid Biopsy is unique because it is a minimally invasive blood test that analyzes cell-free DNA (cfDNA) to provide real-time information about the tumor's genetic makeup, allowing for early diagnosis, monitoring of treatment response, and detection of mutations without needing a traditional tissue biopsy. ^{2 3 4 8 9}

Research Team

Dan Raz

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Treatment of Non-Small-Cell Lung Cancer Based on Circulating Cell-Free DNA and Impact of Variation Allele Frequency. [2022]

2. England pubmed.ncbi.nlm.nih.gov

The role of circulating free DNA in the management of NSCLC. [2019]

3. China pubmed.ncbi.nlm.nih.gov

Possible application of circulating free tumor DNA in non-small cell lung cancer patients. [2020]

4. United States 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. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Liquid biopsies in pediatric oncology: opportunities and obstacles. [2023]

6. England 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. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

An Investigation into Cell-Free DNA in Different Common Cancers. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Liquid biopsy tracking of lung tumor evolutions over time. [2020]

9. Israel pubmed.ncbi.nlm.nih.gov

Early Blood-based Liquid Biopsy in Patients with Treatment-naïve Metastatic Adenocarcinoma of the Lung: A Case Series. [2022]