PROGRESS: Precision Oncology Using Genomic Reflexive Evaluations for Study Selection and Survival

Overview

This is a hybrid decentralized, single-arm, interventional study designed to evaluate the impact of precision medicine navigation and reflexive expert review of next-generation sequencing (NGS) for patients with stage IV solid tumor malignancies (breast, lung, colorectal, and bladder cancers). The purpose of this study is to investigate whether intervention from a centralized precision oncology navigator and expert review of NGS results by the precision oncology pharmacist will increase ordering of Level 1/2 genome informed therapy (GIT) compared to an estimated historical rate of 15%. Secondary endpoints will assess the impact of a centralized precision oncology navigator and expert review of NGS results on enrollment in biomarker-directed clinical trials and overall survival at 2 years after return of NGS results. The study will take approximately 12 months for enrolment and 2 years of follow-up after the date of NGS results.

Detailed description

Despite data supporting a survival benefit in many cancers, rates of NGS testing and subsequent GIT are reported to be low in real-world data sets. Rates of multigene panel-based testing and targeted therapy use are reported to be higher at NCI-designated cancer centers compared to other practice types, even when they are associated with a "hub" site. Molecular tumor boards have demonstrated improvements in overall survival in lung cancer, but these models rely on consults being placed by treating physicians and/or significant institutional resources. Many studies evaluating interventions to increase the use of genome informed therapy (GIT) focus on a single cancer type, thereby hindering the ability to operationalize supportive interventions broadly across all cancer types. Given the collective body of data supporting meaningful clinical improvements when patients have access to GIT, we want to study if interventions that make NGS test ordering and interpretation easier for clinicians will increase the rate of orders for GIT. The use of a centralized precision oncology navigator to facilitate completion of NGS testing, expert clinical review from a clinical pharmacist, and documented clinical decision support embedded in the electronic health record represents a unique and more easily scalable model than full molecular tumor board reviews.

Interventions

• Other Expert Review
  Expert reflexive review of next-generation sequencing (NGS) results will be visible in electronic health records (EPIC) for provider review at the University of North Carolina Health System. Expert review will include recommendations for Genome-informed therapy (GIT), identification of available clinical trials, recommendations for additional testing, and/or referrals for genetic counseling.
• Other Blood or tissue samples collection.
  Blood or tissue samples will be collected for next-generation sequencing (NGS) per standard of care.
• Other The Precision Oncology Navigation
  The precision oncology navigator will coordinate the collection of blood and /or tissue for next-generation sequencing (NGS), as well as order the NGS if not already ordered. Precision oncology navigator will also assist in NGS financial aid applications, if applicable.

Primary outcome measures

• The rate of genome informed therapy (GIT) orders [Time frame: 2 years]

Secondary outcome measures (9)

• Overall survival (OS) [Time frame: 2 years]
• The rate of genome informed therapy (GIT) orders by site [Time frame: 2 years]
• The rates of consent to UNC Health biomarker-selective clinical trials [Time frame: 2 years]
• The reasons for non-consent [Time frame: 2 years]
• Overall Survival in subjects who are eligible for Level 1/2 genome-informed therapy (GIT) [Time frame: 2 years]
• The rates of referrals for full Molecular Tumor Board [Time frame: 2 years]
• The combined rate of orders for Level 1/2 GIT and consent to biomarker-directed clinical trials [Time frame: 2 years]
• The time between the date of NGS results and the Level 1/2 GIT order date [Time frame: 2 years]
• Reasons for lack of Level 1/2 GIT orders in eligible subjects [Time frame: 2 years]

Eligibility criteria

In order to participate in this study a subject must meet all of the eligibility criteria outlined below.

Inclusion criteria

• Written informed consent was obtained to participate in the study and HIPAA authorization for release of personal health information.
• Subjects are willing and able to comply with study procedures based on the judgment of the investigator.
• Age ≥ 18 years at the time of consent.
• ECOG or Karnofsky Performance Status of 0-2.
• Documented Stage IV solid tumor malignancy: NSCLC, CRC, Breast or Bladder Cancer
• The treating provider deems Next Generation Sequencing (NGS) testing appropriate and plans to consider results in either first- or second-line therapy in the metastatic setting
• A genomic tumor test has not been ordered or has been ordered but not resulted.

Exclusion criteria

• Subjects with an active concurrent malignancy.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Lineberger Comprehensive Cancer Center, University of North Carolina — Chapel Hill

Identifiers

NCT: NCT06896162 · LCCC2437-DCT

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗