Liquid Biopsy NGS Prompt for Lung Cancer

(iNUDGE Trial)

Recruiting at 5 trial locations

Overseen By Meagan Hume, MPH

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: Charu Aggarwal

Disqualifiers: Incomplete staging, Children, Pregnant, others

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

Compensation: Varies

Number of Visits: Unknown

360 Participants Needed

Trial Summary

What is the purpose of this trial?

This study expands the application of an electronic health record (EHR) "nudge" used to prompt physicians' clinical practice to order molecular testing at the time of initial diagnosis for patients with specific types of advanced lung cancer. The primary goal is to have these test results available prior to starting treatment so that physicians can make molecularly-informed treatment decisions. The second goal is to better understand factors that contribute to whether or not the EHR-nudge implementation is successful.

Will I have to stop taking my current medications?

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 iNUDGE for lung cancer?

The research highlights that using liquid biopsy with next-generation sequencing (NGS) can help identify important genetic changes in lung cancer, which can guide treatment decisions. This method is especially useful when traditional tissue samples are hard to obtain, suggesting that iNUDGE, if it uses similar technology, could be effective in managing lung cancer. ^{1 2 3 4 5}

Is liquid biopsy NGS safe for humans?

The research does not specifically address safety concerns for liquid biopsy NGS in humans, but it is generally used as a non-invasive alternative to traditional tissue biopsies, which suggests it is considered safe for use in clinical settings. ^{1 2 3 6 7}

How is the Liquid Biopsy NGS treatment different from other treatments for lung cancer?

The Liquid Biopsy NGS treatment is unique because it uses a blood test to analyze cancer DNA, making it less invasive than traditional tissue biopsies. This method can provide a comprehensive view of the cancer's genetic makeup, helping to identify specific targets for treatment and monitor changes over time. ^{1 2 3 5 8}

Research Team

Charu Aggarwal, MD, MPH

Principal Investigator

Penn Medicine

Eligibility Criteria

This trial is for adults with a specific lung cancer type called metastatic non-squamous NSCLC, who haven't started treatment. They must be diagnosed at certain Penn Medicine locations. Pregnant women, children, and prisoners are excluded.

Inclusion Criteria

I have a type of lung cancer called non-squamous NSCLC and haven't been treated for it since it spread.

Participants must be seen at Lancaster General Health (LGH), Penn Presbyterian Medical Center (PPMC), Penn Medicine Cherry Hill (PMCH), Penn Medicine Princeton Health (PMPH), Penn Medicine Voorhees (PMV) or Penn Medicine Washington Township (PMWT) for mNSq NSCLC.

Exclusion Criteria

Children, pregnant women, fetuses, neonates, or prisoners are not included in this research study.

Participants with incomplete staging information.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Intervention

Implementation of EHR-based nudge intervention for molecular testing at initial diagnosis

6 weeks

Regular intervals for cluster randomization

Follow-up

Participants are monitored for the effectiveness of the EHR nudge intervention and molecularly informed treatment initiation

3 months

Evaluation

Semi-structured interviews to evaluate contextual mechanisms and health equity factors

Post-trial period

Treatment Details

Interventions

• iNUDGE

Trial Overview The study tests an 'EHR-nudge' prompting doctors to order molecular testing when diagnosing advanced lung cancer. The aim is to use test results for informed treatment decisions and understand the nudge's effectiveness.

Participant Groups

Group I: Penn Presbyterian Medical Center Experimental Treatment 1 Intervention

All sites with be randomized to implement the nudge at different points in time. Prospective data with be compared with each site's respective baseline numbers over a two-year period.

Group II: Penn Medicine New Jersey Experimental Treatment 1 Intervention

All sites with be randomized to implement the nudge at different points in time. Prospective data with be compared with each site's respective baseline numbers over a two-year period.

Group III: Penn Medicine Lancaster General Health Experimental Treatment 1 Intervention

All sites with be randomized to implement the nudge at different points in time. Prospective data with be compared with each site's respective baseline numbers over a two-year period.

Who Is Running the Clinical Trial?

Charu Aggarwal

Lead Sponsor

Trials

1

Recruited

360+

Loxo Oncology, Inc.

Industry Sponsor

Trials

72

Recruited

11,600+

Jacob Van Naarden

Loxo Oncology, Inc.

Chief Executive Officer since 2019

A.B. in Molecular Biology from Princeton University

Dr. Jennifer Low

Loxo Oncology, Inc.

Chief Medical Officer since 2014

MD and PhD from Georgetown University; Undergraduate degree from California Institute of Technology

Findings from Research

Targeted next generation sequencing (NGS) of liquid biopsies in advanced non-small cell lung cancer (NSCLC) showed a positive percent agreement (PPA) for detecting mutations, with the highest rate of 67.8% for EGFR, indicating that while liquid biopsies can identify some mutations, they may not fully replace tissue biopsies.

Liquid biopsies can be a useful tool for therapeutic decision-making in NSCLC, but they currently do not detect all clinically relevant mutations as effectively as tissue biopsies, highlighting the need for further research to establish their role in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of liquid-based to tissue-based biopsy analysis by targeted next generation sequencing in advanced non-small cell lung cancer: a comprehensive systematic review. Esagian, SM., Grigoriadou, GΙ., Nikas, IP., et al.[2021]

Liquid biopsy has transformed cancer management by effectively identifying actionable cancer markers, especially when traditional tissue biopsies are not possible.

Next generation sequencing applied to liquid biopsy enhances tumor genotyping and monitoring, making it a powerful tool for early detection and understanding resistance mechanisms in lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The evolving role of liquid biopsy in lung cancer. Malapelle, U., Pisapia, P., Pepe, F., et al.[2022]

Next-generation sequencing (NGS) from plasma samples in treatment-naïve patients with non-squamous cell lung carcinoma (NSCC) is feasible and shows good correlation with tissue-based testing, indicating its potential utility in clinical practice.

However, in this study of 24 patients, the impact of liquid biopsy on therapy selection was limited, and it could not replace traditional tissue testing for guiding treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective evaluation of NGS-based liquid biopsy in untreated late stage non-squamous lung carcinoma in a single institution. Heeke, S., Hofman, V., Ilié, M., et al.[2021]

In a study of 24 advanced non-small cell lung cancer (NSCLC) patients, liquid biopsies revealed potential resistance mechanisms in 57% of those progressing on targeted therapies, highlighting the importance of genetic analysis in treatment planning.

The most common resistance mechanisms identified were mutations in ALK and EGFR, found in 38% of patients, indicating that monitoring these genetic changes can inform oncologists about the effectiveness of ongoing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective analysis of liquid biopsies of advanced non-small cell lung cancer patients after progression to targeted therapies using GeneReader NGS platform. Mayo de Las Casas, C., Garzón-Ibañez, M., Jordana-Ariza, N., et al.[2022]

Next-generation sequencing (NGS) combined with liquid biopsy represents a significant advancement in the precision medicine approach for non-small cell lung cancer (NSCLC), allowing for comprehensive genomic profiling in a minimally invasive way.

This method not only helps identify actionable genomic alterations but also enables dynamic monitoring of tumor evolution and treatment responses, highlighting its potential for improving diagnosis and treatment strategies in NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The emerging roles of NGS-based liquid biopsy in non-small cell lung cancer. Zhang, YC., Zhou, Q., Wu, YL.[2023]

Liquid biopsies, which analyze circulating tumor DNA (ctDNA), provide a non-invasive way to gather comprehensive tumor information, making them a promising tool for monitoring lung cancer and identifying genetic alterations.

These blood-based tests can detect genetic changes before they are visible through traditional imaging, allowing for earlier intervention and personalized treatment adjustments based on the tumor's genetic profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liquid biopsies in lung cancer-time to implement research technologies in routine care? Köhn, L., Johansson, M., Grankvist, K., et al.[2020]

The SiRe next-generation sequencing (NGS) panel effectively identified somatic mutations in lung cancer tissue samples, with only 8.7% of specimens failing to produce usable data, demonstrating its reliability in clinical settings.

In a small group of 11 patients treated based on SiRe results, 82% showed a partial response to treatment, with a median progression-free survival of 340 days, indicating promising efficacy for guiding therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Performance analysis of SiRe next-generation sequencing panel in diagnostic setting: focus on NSCLC routine samples. Pepe, F., De Luca, C., Smeraglio, R., et al.[2018]

The study identified hypermethylation of the CFTR gene in the plasma of non-small-cell lung carcinoma (NSCLC) patients, indicating it could serve as a potential blood-based biomarker for diagnosing NSCLC.

The CFTR promoter showed a sensitivity of 52% and a specificity of 90% in distinguishing NSCLC patients from those without malignancy, suggesting it has promising diagnostic potential that warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Liquid biopsy in human non-small-cell lung cancer : Blood-based analysis of ctDNA methylation]. Schulz, H., Tator, M., Spillner, J., et al.[2020]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Comparison of liquid-based to tissue-based biopsy analysis by targeted next generation sequencing in advanced non-small cell lung cancer: a comprehensive systematic review. [2021]

2. Ireland pubmed.ncbi.nlm.nih.gov

The evolving role of liquid biopsy in lung cancer. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Prospective evaluation of NGS-based liquid biopsy in untreated late stage non-squamous lung carcinoma in a single institution. [2021]

4. China pubmed.ncbi.nlm.nih.gov

Prospective analysis of liquid biopsies of advanced non-small cell lung cancer patients after progression to targeted therapies using GeneReader NGS platform. [2022]

5. England pubmed.ncbi.nlm.nih.gov

The emerging roles of NGS-based liquid biopsy in non-small cell lung cancer. [2023]

6. China pubmed.ncbi.nlm.nih.gov

Liquid biopsies in lung cancer-time to implement research technologies in routine care? [2020]

7. England pubmed.ncbi.nlm.nih.gov

Performance analysis of SiRe next-generation sequencing panel in diagnostic setting: focus on NSCLC routine samples. [2018]

8. Germany pubmed.ncbi.nlm.nih.gov

[Liquid biopsy in human non-small-cell lung cancer : Blood-based analysis of ctDNA methylation]. [2020]