Clinical trial NCT05853887: Liquid Biopsy Based NGS in Newly Diagnosed NSCLC
Official title: iNUDGE: INtegration of liqUiD Biopsy Based Next Generation Gene sEquencing in Newly Diagnosed NSCLC - A Stepped Wedge Cluster Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Non Small Cell Lung Cancer Metastatic
Newly Diagnosed NSCLC
Non-Squamous Non-Small Cell Neoplasm of Lung
Keywords: Next Generation Sequencing
Liquid biopsy
Newly diagnosed
Molecular testing
Plasma based next generation sequencing
Electronic health record
Nudge intervention
Targeted therapy
Behavioral economics
Lead sponsor: Abramson Cancer Center at Penn Medicine
Sponsor class: OTHER
Collaborators: name: Loxo Oncology, Inc.
First posted: 2023-05-11
Enrollment: 360
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 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 purpose: HEALTH_SERVICES_RESEARCH

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Availability of comprehensive molecular test results prior to first line therapy for patients with newly diagnosed mNSq NSCLC
timeFrame: Measured up to 6 weeks from initial diagnosis
Secondary outcomes:
measure: Successful EHR based nudge delivery
timeFrame: Measured up to 6 weeks from randomization
measure: Turnaround time of delivery of provider focused alerts
timeFrame: Measured up to 6 weeks from randomization
measure: Completion of comprehensive molecular testing & modality used
timeFrame: Measured up to 3 months from initial diagnosis
measure: Reasons for failure to complete comprehensive molecular testing:
timeFrame: Measured up to 3 months from initial diagnosis
measure: Time to molecularly informed treatment initiation
timeFrame: Measured up to 6 weeks from initial diagnosis
measure: Type of therapy received
timeFrame: Measured up to 3 months from initial diagnosis
measure: Overall survival
timeFrame: Measured up to 1 year from the time of randomization to death from any cause
Other outcomes:
Locations:
city: Cherry Hill
country: United States
facility: Penn Medicine Cherry Hill
state: New Jersey
city: Plainsboro
country: United States
facility: Penn Medicine Princeton Health
state: New Jersey
city: Sewell
country: United States
facility: Penn Medicine Washington Township
state: New Jersey
city: Voorhees
country: United States
facility: Penn Medicine Voorhees
state: New Jersey
city: Lancaster
country: United States
facility: Penn Medicine Lancaster General Health
state: Pennsylvania
city: Philadelphia
country: United States
facility: Penn Presbyterian Medical Center
state: Pennsylvania
Study officials:
affiliation: Penn Medicine
name: Charu Aggarwal, MD, MPH
role: PRINCIPAL_INVESTIGATOR
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