Liquid Biopsy Based NGS in Newly Diagnosed NSCLC

NCT ID: NCT05853887

Last Updated: 2025-11-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

360 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-06-15

Study Completion Date

2026-01-31

Brief Summary

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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.

Detailed Description

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At the University of Pennsylvania Health System (UPHS), a behavioral economics (BE) informed "nudge" strategy was piloted to guide physicians' clinical practice to include concurrent use of plasma and tissue-based next generation sequencing (NGS) testing at the time of initial diagnosis for patients with newly diagnosed metastatic non-squamous (mNSq) non-small cell lung cancer (NSCLC). These findings have demonstrated that behavioral, electronic health record (EHR)-based nudges are feasible and can promote guideline concordant diagnostic testing at both community and academic sites.

The overarching goal of this current trial is to expand the application of the BE informed nudges, which includes a Best Practice Advisory (BPA) and Electronic Decision Support Tool (e-CDS) approach, which has been operationalized within Epic, the EHR used at UPHS, to six satellite hospitals. Our central hypothesis is that this approach will dramatically increase adoption of comprehensive molecular testing and enhance the delivery of molecularly informed 1L therapy in patients with newly diagnosed mNSq NSCLC.

Intervention: A multicomponent BE-informed EHR-based nudge designed to facilitate comprehensive molecular testing by embedding a default P-NGS order into the EHR at the time of the NPV. If ordered, test results are incorporated into provider workflows and conveyed through electronic clinical decision support (e-CDS) notifications. This support program will notify clinicians of targetable mutations, potential clinical trials, as well as absence of mutations detected on plasma testing as a means of improving the timely delivery of molecularly informed therapy.

Study Design

Objective 1: In a stepped wedge cluster randomized trial of newly diagnosed patients with mNSq NSCLC, evaluate the effectiveness of a multicomponent BE-informed EHR-based nudge intervention at increasing timely receipt of comprehensive molecular test results prior to 1L therapy by incorporating P-NGS into the standard clinical workup.

The design of this trial will include 3 clusters, representing 6 community hospitals. There will be an initial period in which no clusters are exposed to the intervention. Subsequently, at regular intervals (the "steps") one cluster (or a group of clusters) will be randomized to cross from the control to the intervention under evaluation. This process will continue until all clusters have crossed over to be exposed to the intervention. At the end of the study there will be a period when all clusters are exposed. Data collection will continue throughout the study, so that each cluster will contribute observations under both control and intervention observation periods. Two years of baseline data will be obtained from all study sites for comparison.

Objective 2: Assess the contextual mechanisms influencing the adoption, reach, and effectiveness of EHR-based nudge interventions, with a lens for health equity in molecular testing using mixed-methods.

Using rigorous approaches proven successful in our prior work, we will recruit patient and clinician participants from each site to complete semi-structured interviews and structured questionnaires. The goal of this objective is to understand contextual mechanisms (e.g., patient, clinician, clinic, structural factors) shaping adoption, reach, and effectiveness of each intervention and identify how response may differ by key characteristics. These data will be analyzed using convergent mixed methods analysis, which employs the simultaneous collection and analysis of both quantitative and qualitative data to gain a comprehensive understanding of the multi-level factors shaping trial outcomes.

Conditions

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Non Small Cell Lung Cancer Metastatic Newly Diagnosed NSCLC Non-Squamous Non-Small Cell Neoplasm of Lung

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

This study employs a stepped-wedge cluster randomized clinical trial design. Randomization will occur at the group (site) level. Sites will be turned on according to the stepped-wedge cluster randomized design but will run in parallel.
Primary Study Purpose

HEALTH_SERVICES_RESEARCH

Blinding Strategy

NONE

This intervention is directed towards physicians. Individuals will not be randomized.

Study Groups

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Penn Medicine New Jersey

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 Type OTHER

iNUDGE

Intervention Type BEHAVIORAL

Electronic health record nudge which prompts physicians to order plasma-based NGS testing for eligible patients with newly diagnosed lung cancer.

Penn Medicine Lancaster General Health

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 Type OTHER

iNUDGE

Intervention Type BEHAVIORAL

Electronic health record nudge which prompts physicians to order plasma-based NGS testing for eligible patients with newly diagnosed lung cancer.

Penn Presbyterian Medical Center

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 Type OTHER

iNUDGE

Intervention Type BEHAVIORAL

Electronic health record nudge which prompts physicians to order plasma-based NGS testing for eligible patients with newly diagnosed lung cancer.

Interventions

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iNUDGE

Electronic health record nudge which prompts physicians to order plasma-based NGS testing for eligible patients with newly diagnosed lung cancer.

Intervention Type BEHAVIORAL

Eligibility Criteria

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Inclusion Criteria

* Participants with a histological, or cytological diagnosis of metastatic non-squamous (mNSq) non-small cell lung cancer (NSCLC) who have not yet received systemic treatment for metastatic disease.
* 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

* Participants with incomplete staging information.
* Children, pregnant women, fetuses, neonates, or prisoners are not included in this research study.
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Eli Lilly and Company

INDUSTRY

Sponsor Role collaborator

Charu Aggarwal

OTHER

Sponsor Role lead

Responsible Party

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Charu Aggarwal

Leslye M. Heisler Associate Professor of Lung Cancer Excellence and Associate Director, Penn Center for Precision Medicine

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Charu Aggarwal, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Penn Medicine

Locations

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Penn Medicine Cherry Hill

Cherry Hill, New Jersey, United States

Site Status RECRUITING

Penn Medicine Princeton Health

Plainsboro, New Jersey, United States

Site Status RECRUITING

Penn Medicine Washington Township

Sewell, New Jersey, United States

Site Status RECRUITING

Penn Medicine Voorhees

Voorhees Township, New Jersey, United States

Site Status RECRUITING

Penn Medicine Lancaster General Health

Lancaster, Pennsylvania, United States

Site Status RECRUITING

Penn Presbyterian Medical Center

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Anthony Martella, MBMI

Role: CONTACT

267-809-7089

Facility Contacts

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Shayma Kazmi, MD

Role: primary

Ramy Sedhom, MD

Role: primary

Shayma Kazmi, MD

Role: primary

Shayma Kazmi, MD

Role: primary

Samuel J Kerr, MD

Role: primary

Christopher A D'Avella, MD

Role: primary

Christine Ciunci, MD

Role: backup

References

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Aggarwal C, Rolfo CD, Oxnard GR, Gray JE, Sholl LM, Gandara DR. Strategies for the successful implementation of plasma-based NSCLC genotyping in clinical practice. Nat Rev Clin Oncol. 2021 Jan;18(1):56-62. doi: 10.1038/s41571-020-0423-x. Epub 2020 Sep 11.

Reference Type BACKGROUND
PMID: 32918064 (View on PubMed)

Rolfo C, Mack P, Scagliotti GV, Aggarwal C, Arcila ME, Barlesi F, Bivona T, Diehn M, Dive C, Dziadziuszko R, Leighl N, Malapelle U, Mok T, Peled N, Raez LE, Sequist L, Sholl L, Swanton C, Abbosh C, Tan D, Wakelee H, Wistuba I, Bunn R, Freeman-Daily J, Wynes M, Belani C, Mitsudomi T, Gandara D. Liquid Biopsy for Advanced NSCLC: A Consensus Statement From the International Association for the Study of Lung Cancer. J Thorac Oncol. 2021 Oct;16(10):1647-1662. doi: 10.1016/j.jtho.2021.06.017. Epub 2021 Jul 8.

Reference Type BACKGROUND
PMID: 34246791 (View on PubMed)

Robert NJ, Espirito JL, Chen L, Nwokeji E, Karhade M, Evangelist M, Spira A, Neubauer M, Bullock S, Walberg J, Cheng SK, Coleman RL. Biomarker testing and tissue journey among patients with metastatic non-small cell lung cancer receiving first-line therapy in The US Oncology Network. Lung Cancer. 2022 Apr;166:197-204. doi: 10.1016/j.lungcan.2022.03.004. Epub 2022 Mar 10.

Reference Type BACKGROUND
PMID: 35313244 (View on PubMed)

Singal G, Miller PG, Agarwala V, Li G, Kaushik G, Backenroth D, Gossai A, Frampton GM, Torres AZ, Lehnert EM, Bourque D, O'Connell C, Bowser B, Caron T, Baydur E, Seidl-Rathkopf K, Ivanov I, Alpha-Cobb G, Guria A, He J, Frank S, Nunnally AC, Bailey M, Jaskiw A, Feuchtbaum D, Nussbaum N, Abernethy AP, Miller VA. Association of Patient Characteristics and Tumor Genomics With Clinical Outcomes Among Patients With Non-Small Cell Lung Cancer Using a Clinicogenomic Database. JAMA. 2019 Apr 9;321(14):1391-1399. doi: 10.1001/jama.2019.3241.

Reference Type BACKGROUND
PMID: 30964529 (View on PubMed)

Thompson JC, Yee SS, Troxel AB, Savitch SL, Fan R, Balli D, Lieberman DB, Morrissette JD, Evans TL, Bauml J, Aggarwal C, Kosteva JA, Alley E, Ciunci C, Cohen RB, Bagley S, Stonehouse-Lee S, Sherry VE, Gilbert E, Langer C, Vachani A, Carpenter EL. Detection of Therapeutically Targetable Driver and Resistance Mutations in Lung Cancer Patients by Next-Generation Sequencing of Cell-Free Circulating Tumor DNA. Clin Cancer Res. 2016 Dec 1;22(23):5772-5782. doi: 10.1158/1078-0432.CCR-16-1231. Epub 2016 Sep 6.

Reference Type BACKGROUND
PMID: 27601595 (View on PubMed)

Leighl NB, Page RD, Raymond VM, Daniel DB, Divers SG, Reckamp KL, Villalona-Calero MA, Dix D, Odegaard JI, Lanman RB, Papadimitrakopoulou VA. Clinical Utility of Comprehensive Cell-free DNA Analysis to Identify Genomic Biomarkers in Patients with Newly Diagnosed Metastatic Non-small Cell Lung Cancer. Clin Cancer Res. 2019 Aug 1;25(15):4691-4700. doi: 10.1158/1078-0432.CCR-19-0624. Epub 2019 Apr 15.

Reference Type BACKGROUND
PMID: 30988079 (View on PubMed)

Whitaker RG, Sperber N, Baumgartner M, Thiem A, Cragun D, Damschroder L, Miech EJ, Slade A, Birken S. Coincidence analysis: a new method for causal inference in implementation science. Implement Sci. 2020 Dec 11;15(1):108. doi: 10.1186/s13012-020-01070-3.

Reference Type BACKGROUND
PMID: 33308250 (View on PubMed)

Aggarwal C, Thompson JC, Black TA, Katz SI, Fan R, Yee SS, Chien AL, Evans TL, Bauml JM, Alley EW, Ciunci CA, Berman AT, Cohen RB, Lieberman DB, Majmundar KS, Savitch SL, Morrissette JJD, Hwang WT, Elenitoba-Johnson KSJ, Langer CJ, Carpenter EL. Clinical Implications of Plasma-Based Genotyping With the Delivery of Personalized Therapy in Metastatic Non-Small Cell Lung Cancer. JAMA Oncol. 2019 Feb 1;5(2):173-180. doi: 10.1001/jamaoncol.2018.4305.

Reference Type BACKGROUND
PMID: 30325992 (View on PubMed)

Shelton RC, Chambers DA, Glasgow RE. An Extension of RE-AIM to Enhance Sustainability: Addressing Dynamic Context and Promoting Health Equity Over Time. Front Public Health. 2020 May 12;8:134. doi: 10.3389/fpubh.2020.00134. eCollection 2020.

Reference Type BACKGROUND
PMID: 32478025 (View on PubMed)

Rendle KA, Abramson CM, Garrett SB, Halley MC, Dohan D. Beyond exploratory: a tailored framework for designing and assessing qualitative health research. BMJ Open. 2019 Aug 27;9(8):e030123. doi: 10.1136/bmjopen-2019-030123.

Reference Type BACKGROUND
PMID: 31462482 (View on PubMed)

Kane H, Lewis MA, Williams PA, Kahwati LC. Using qualitative comparative analysis to understand and quantify translation and implementation. Transl Behav Med. 2014 Jun;4(2):201-8. doi: 10.1007/s13142-014-0251-6.

Reference Type BACKGROUND
PMID: 24904704 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol: Revised iNUDGE Protocol 04.08.2025

View Document

Document Type: Study Protocol and Statistical Analysis Plan: Original Protocol 03.24.2023

View Document

Document Type: Statistical Analysis Plan: iNUDGE Statistical Analysis Plan 04.30.2025

View Document

Other Identifiers

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852795

Identifier Type: OTHER

Identifier Source: secondary_id

UPCC 27522

Identifier Type: -

Identifier Source: org_study_id

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