Machine Learning Approaches to Personalized Therapy for Advanced Non-small Cell Lung Cancer With Real-World Data

April 28, 2026 updated by: University of Utah
This research will leverage machine learning (ML) and causal inference techniques applied to real-world data (RWD) to generate evidence that personalizes treatment strategies for patients with advanced non-small cell lung cancer (aNSCLC). Rather than influencing regulatory decisions or clinical guidelines, the goal of this trial is to refine treatment selection among existing therapeutic options, ensuring that care is tailored to individual patient characteristics. Additionally, by generating real-world evidence, these findings will inform the design and implementation of future clinical trials. Importantly, the methodological advancements will establish a pipeline that extends beyond aNSCLC, facilitating the identification of optimal dynamic treatment regimes (DTRs) for other complex diseases.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Detailed Description

The proposed research will enhance patient-centered outcomes research (PCOR) and comparative effectiveness research (CER) methodologies by addressing two key challenges: (1) appropriate handling of missing EHR data and (2) rigorous causal inference techniques for sequential treatment strategies. By focusing on treatment strategies tailored to individual patients and incorporating patient-reported outcomes (PROs), this study is fundamentally patient-centered. Furthermore, the research is guided by practicing physicians, a patient advocate, and a former patient caregiver, ensuring that it remains aligned with the needs and priorities of those directly affected by aNSCLC.

This study will develop novel reinforcement learning algorithms by integrating multiply robust matching-based approaches. This study will tailor each component of DTR to optimize treatment sequences for aNSCLC patients, leveraging two large-scale, high-quality nationwide real-world electronic health record (EHR) databases: the Flatiron aNSCLC database and the CancerLinQ lung cancer database. These databases provide comprehensive clinicodemographic and longitudinal patient data.

Additionally, incorporating PRO data from two National Cancer Institute (NCI)-designated Comprehensive Cancer Centers -Huntsman Cancer Institute (HCI) and Moffitt Cancer Center (MCC) - will enable this trial to capture the patient perspective when personalizing aNSCLC care recommendations. Key outcomes will include overall survival, quality-adjusted life years (QALYs), time to second progression or death (PFS2), and time to worsening of selected PROs, all framed as time-to-event outcomes.

These methodological innovations will establish a reproducible pipeline for translating real-world evidence from large-scale EHR data into personalized DTR recommendations for aNSCLC patients and other complex disease populations.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
144400

Contacts and Locations

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

Study Locations

  • United States
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Recruiting
        • Huntsman Cancer Institute at the University of Utah
        • Contact:
        • Principal Investigator:
          • Jincheng Shen, Ph.D.

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

The primary research focus is on non-small cell lung cancer (NSCLC), which accounts for 85% of all lung cancer cases and remains a leading cause of cancer mortality in the United States. This study will use de-identified EHR data from two large nationwide databases - Flatiron and CancerLinQ - as well as de-identified data from Huntsman Cancer Institute (HCI) and Moffitt Cancer Center (MCC) to gain insights into personalized aNSCLC care.

Description

Inclusion Criteria

Subjects must meet all of the following eligibility criteria:

  • Diagnosed with advanced NSCLC between January 1, 2011, and June 30, 2024.
  • Follow-up available until December 31, 2024, with a minimum potential follow-up period of at least six months.

Exclusion Criteria

Subjects meeting any of the following criteria at baseline will be excluded:

  • Fewer than one day of follow-up post-initiation of first-line (1L) therapy.
  • Presence of a targetable mutation, including ALK, BRAF, EGFR, KRAS, or ROS1.
  • PD-L1 expression <50% at baseline (restricted to patients with PD-L1 ≥50%).
  • First-line treatment limited to immunotherapy or chemoimmunotherapy (excluding other treatment regimens).
  • Patients receiving second-line (2L) treatment, including those enrolled in a clinical 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

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Flatiron database
The current study will utilize data from national EHR databases (Flatiron and CancerLinQ) and existing cohort data (HCI and MCC). Only de-identified data will be used, and no patients will be contacted during the study.
CancerLinQ database
The current study will utilize data from national EHR databases (Flatiron and CancerLinQ) and existing cohort data (HCI and MCC). Only de-identified data will be used, and no patients will be contacted during the study.
Huntsman Cancer Institute (HCI) Cohort
The current study will utilize data from national EHR databases (Flatiron and CancerLinQ) and existing cohort data (HCI and MCC). Only de-identified data will be used, and no patients will be contacted during the study.
Moffitt Cancer Center (MCC) Cohort
The current study will utilize data from national EHR databases (Flatiron and CancerLinQ) and existing cohort data (HCI and MCC). Only de-identified data will be used, and no patients will be contacted during the study.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: From the initiation of first-line therapy to death or the last follow-up, whichever occurs first, up to 10 years.

Mortality is the primary concern in aNSCLC care. This study will track survival from the initiation of first-line therapy to death or the last follow-up, whichever occurs first.

OS will be censored at the last recorded date in the electronic health records.
From the initiation of first-line therapy to death or the last follow-up, whichever occurs first, up to 10 years.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Quality-Adjusted Life Years (QALYs)
Time Frame: From the initiation of first-line therapy to death or the last follow-up, whichever occurs first, up to 2 years.
Assessed within two years after treatment initiation.
From the initiation of first-line therapy to death or the last follow-up, whichever occurs first, up to 2 years.
Time to second progression or death (PFS2)
Time Frame: From the initiation of first-line therapy to second disease progression, death, or the last follow-up, whichever occurs first, up to 10 years.
Time from treatment initiation to second disease progression or death, whichever occurs first.
From the initiation of first-line therapy to second disease progression, death, or the last follow-up, whichever occurs first, up to 10 years.
National Cancer Institute (NCI) Patient-Reported Outcomes Measurement Information System-Cancer (PROMIS-Ca)
Time Frame: From the initiation of first-line therapy to worsening or the last follow-up, whichever occurs first, up to 10 years.

PROs were collected using the NCI PROMIS-Ca Bank at the Huntsman Cancer Institute. Six PROMIS-Ca scales were utilized: the 17-item Fatigue scale (Fatigue-17), the 7-item PROMIS Fatigue scale (Fatigue-7), the 10-item Pain Interference scale (PainInt-10), the 10-item Physical Function scale (PhysFunc-10), the 9-item Anxiety scale (Anxiety-9), and the 10-item Depression scale (Depression-10).

Each item was rated on a 5-point ordinal scale, with all PROMIS-Ca scales scored so that higher scores indicate greater levels of the respective concept (e.g., a higher Fatigue-7 score reflects greater fatigue, while a higher PhysFunc-10 score denotes better physical functioning).

Raw scores were calculated as the prorated sum of item responses when at least 50% of the items on a scale were completed. T-scores were derived using a reference population with a mean of 50 and a standard deviation of 10. This outcome measure will report each T-score (range: 0-100).
From the initiation of first-line therapy to worsening or the last follow-up, whichever occurs first, up to 10 years.
Edmonton Symptom Assessment System (ESAS) Outcomes
Time Frame: From the initiation of first-line therapy to worsening or the last follow-up, whichever occurs first, up to 10 years.

The Edmonton Symptom Assessment System (ESAS) was used to evaluate 9 common symptoms: pain, tiredness, drowsiness, nausea, lack of appetite, shortness of breath, depression, anxiety, and overall well-being. Symptoms were rated on an 11-point scale ranging from 0 (no symptom burden) to 10 (worst symptom burden). Moffitt employs a modified version of the ESAS that includes two additional symptoms: constipation and sleep disturbance.

ESAS will be analyzed using a time-to-worsening framework, with a worsening benchmark of ≥2 points for ESAS-both representing approximately twice the minimally important difference.
From the initiation of first-line therapy to worsening or the last follow-up, whichever occurs first, up to 10 years.

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Utah

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Patient-Centered Outcomes Research Institute

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 31, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 31, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 28, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 10, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 18, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 4, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 28, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • HCI183476
  • ME-2023C2-33957 (Other Grant/Funding Number: Patient-Centered Outcomes Research Institute)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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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