Liquid Biopsy Based NGS in Newly Diagnosed NSCLC (iNUDGE)

February 15, 2024 updated by: Charu Aggarwal

iNUDGE: INtegration of liqUiD Biopsy Based Next Generation Gene sEquencing in Newly Diagnosed NSCLC - A Stepped Wedge Cluster Randomized Clinical 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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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 this BE informed nudge 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.

Molecular testing will be defined as i) comprehensive: EGFR, ALK, BRAF, ROS1, MET, RET, and NTRK testing, ii) incomplete: <6 genes tested, and iii) no testing performed. Clinically actionable mutations will be defined as an alteration in one of the seven genes on the comprehensive gene list with an FDA approved targeted therapy in the 1L setting, plus KRAS G12C, EGFR exon 20 insertion, and ErbB2 mutations. Molecularly informed first line therapy will be defined as one that is informed by results of NGS, obtained by plasma, tissue or both.

Intervention

An EHR-based nudge intervention that allows for default placement of a plasma based molecular genotyping order at time of the first new patient visit will be implemented. Subsequently, results detected on the default plasma NGS order will be conveyed to providers in the form of an electronic clinical decision support notification.

As part of the downstream EHR-based nudge intervention workflow, an electronic clinical decision support (e-CDS) system for alterations detected on plasma genotyping will be created and implemented into the EHR as a "Research (non-chargeable) Encounter" to alert the provider team caring for the patient. This support program will be created to notify clinicians of targetable mutations, 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 patients with newly diagnosed mNSq NSCLC, test the effectiveness of a behavioral economics (BE) informed EHR nudge intervention to increase timely receipt of comprehensive molecular test results before 1L therapy by integration of concurrent tissue and plasma molecular testing.

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: Evaluate contextual mechanisms contributing to the adoption, reach, and effectiveness of EHR nudge interventions with a lens for health equity.

Using rigorous approaches proven successful in our prior work, the investigators will recruit 10-15 patient and clinician participants from each site (estimated 40-60 participants total) to complete semi-structured interviews following the active trial period. 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 race and ethnicity, socioeconomic status, and other key social determinants of health. These data will be analyzed using qualitative comparative analysis, a mixed method approach well suited to identify mechanisms in pragmatic trials with smaller sample sizes.

Study Type

Interventional

Enrollment (Estimated)

360

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • New Jersey
      • Cherry Hill, New Jersey, United States, 08003
        • Recruiting
        • Penn Medicine Cherry Hill
        • Contact:
          • Shayma Kazmi, MD
        • Sub-Investigator:
          • Shayma Kazmi, MD
      • Plainsboro, New Jersey, United States, 08536
        • Recruiting
        • Penn Medicine Princeton Health
        • Contact:
          • Ramy Sedhom, MD
        • Sub-Investigator:
          • Ramy Sedhom, MD
      • Sewell, New Jersey, United States, 08080
        • Recruiting
        • Penn Medicine Washington Township
        • Contact:
          • Shayma Kazmi, MD
        • Sub-Investigator:
          • Shayma Kazmi, MD
      • Voorhees, New Jersey, United States, 08043
        • Recruiting
        • Penn Medicine Voorhees
        • Contact:
          • Shayma Kazmi, MD
    • Pennsylvania
      • Lancaster, Pennsylvania, United States, 17602
        • Recruiting
        • Penn Medicine Lancaster General Health
        • Contact:
          • Samuel J Kerr, MD
        • Sub-Investigator:
          • Samuel J Kerr, MD
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • Penn Presbyterian Medical Center
        • Contact:
          • Christopher A D'Avella, MD
        • Contact:
          • Christine Ciunci, MD
        • Sub-Investigator:
          • Christopher A D'Avella, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Health Services Research
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: 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.
Behavioral: iNUDGE
Electronic health record nudge which prompts physicians to order plasma-based NGS testing for eligible patients with newly diagnosed lung cancer.
Other: 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.
Behavioral: iNUDGE
Electronic health record nudge which prompts physicians to order plasma-based NGS testing for eligible patients with newly diagnosed lung cancer.
Other: 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.
Behavioral: iNUDGE
Electronic health record nudge which prompts physicians to order plasma-based NGS testing for eligible patients with newly diagnosed lung cancer.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Availability of comprehensive molecular test results prior to first line therapy for patients with newly diagnosed mNSq NSCLC
Time Frame: Measured up to 6 weeks from initial diagnosis
Were comprehensive molecular test results available prior to initiation of 1L therapy? (Yes/No)
Measured up to 6 weeks from initial diagnosis

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Successful EHR based nudge delivery
Time Frame: Measured up to 6 weeks from randomization
Amongst eligible patients, calculate the proportion of patients for whom the EHR nudge fired successfully (Yes/No). Applicable for the patients enrolled in the time periods following randomization.
Measured up to 6 weeks from randomization
Turnaround time of delivery of provider focused alerts
Time Frame: Measured up to 6 weeks from randomization
Reported as number of days, median. Applicable for the patients enrolled in the time periods following randomization.
Measured up to 6 weeks from randomization
Completion of comprehensive molecular testing & modality used
Time Frame: Measured up to 3 months from initial diagnosis
Relative and absolute change in completion of comprehensive testing by tissue and plasma, plasma alone, or tissue alone will be tabulated.
Measured up to 3 months from initial diagnosis
Reasons for failure to complete comprehensive molecular testing:
Time Frame: Measured up to 3 months from initial diagnosis
Summarize reasons for failure of completion of testing i. Tissue related (QNS) ii. Patient related factors (unable to biopsy, patient declined biopsy etc.) iii. Assay related factors (plasma assay does not detect mutations) iv. Other
Measured up to 3 months from initial diagnosis
Time to molecularly informed treatment initiation
Time Frame: Measured up to 6 weeks from initial diagnosis
i. Calculated as time to therapy from the date of diagnosis of Stage IV disease (date of biopsy) ii. Calculated as time to therapy from the date of first new patient visit with medical oncology
Measured up to 6 weeks from initial diagnosis
Type of therapy received
Time Frame: Measured up to 3 months from initial diagnosis
i. Targeted therapy ii. Chemo-immunotherapy iii. Immunotherapy iv. Clinical trial or n v. None
Measured up to 3 months from initial diagnosis
Overall survival
Time Frame: Measured up to 1 year from the time of randomization to death from any cause
i. Time from initial diagnosis to date of death or last follow up. ii. 1 year and 2-year overall survival rates will be calculated for the intervention group, and compared to baseline.
Measured up to 1 year from the time of randomization to death from any cause

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Charu Aggarwal

Collaborators

Loxo Oncology, Inc.

Investigators

  • Principal Investigator: Charu Aggarwal, MD, MPH, Penn Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 15, 2023

Primary Completion (Estimated)

June 1, 2025

Study Completion (Estimated)

December 1, 2025

Study Registration Dates

First Submitted

April 7, 2023

First Submitted That Met QC Criteria

May 9, 2023

First Posted (Actual)

May 11, 2023

Study Record Updates

Last Update Posted (Actual)

February 16, 2024

Last Update Submitted That Met QC Criteria

February 15, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UPCC 27522
  • 852795 (Other Identifier: University of Pennsylvania Institutional Review Board)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

A Clinical Study Report will be made available to the study sponsor.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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