A Prospective Study Investigating the Relationship Between Minimal Residual Disease Detection, Monitoring Frequency, and Prognosis in Non-small Cell Lung Cancer Patients Eligible for Curative Treatment. (MRDSEEKER)

Prospective Observational Study Using Personalized Minimal Residual Disease Assay (Signatera) to Evaluate the Kinetics and Detection Rate in Patients with Non-small Cell Lung Cancer

Adding immune checkpoint inhibitors or molecularly targeted drugs as adjuvant therapy to curative treatments-such as surgery or chemoradiotherapy-for stage I-III non-small cell lung cancer (NSCLC) has been established as a standard of care and has improved treatment outcomes. However, there is currently no adequate method to determine which patients should receive these adjuvant therapies. Identifying those with a good prognosis without adjuvant therapy could reduce the risk of adverse events, lessen the burden of clinic visits, and reduce healthcare costs.

Among various approaches, ctDNA-based MRD (minimal residual disease) analysis is highly anticipated and has already been introduced into clinical practice for hematologic malignancies. However, solid tumors' development as a companion diagnostic has been limited, and regulatory approval is mainly being considered based on performance evaluation data. In this study, we will conduct a performance evaluation of MRD analysis using Signatera™ in patients with stage I-III NSCLC while also collecting other prognostic factors based on clinicopathological information and survival data.

Study Overview

• Status: Not yet recruiting
• Conditions: NSCLC, Stage I, II, III

• Study Type: Observational
• Enrollment (Estimated): 350

Contacts and Locations

Study Locations

• Japan
  • Tokyo
    • Chuo-ku, Tokyo, Japan
      • National Cancer Center Hospital
      • Contact: Hidehito Horinouchi, MD, PhD; Phone Number: +813-3542-2511; Email: hhorinou@ncc.go.jp
      • Contact: Ken Masuda, MD; Phone Number: +813-3542-2511; Email: kenmasud@ncc.go.jp
      • Contact: Hidehito Horinouchi, MD, PhD
      • Contact: Ken Masuda, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

non-small cell lung cancer (NSCLC)

Description

Inclusion Criteria:

1. A histopathologically confirmed diagnosis of non-small cell lung cancer (NSCLC)

   The diagnosis (by cytology or biopsy) must be one of the following: "adenocarcinoma," "squamous cell carcinoma," "non-small cell carcinoma consistent with adenocarcinoma," "non-small cell carcinoma consistent with squamous cell carcinoma," or "non-small cell carcinoma not otherwise specified (NOS)." If the histological subtype differs between cytology and biopsy specimens, the subtype determined by the biopsy specimen shall be used.

   At the time of enrollment, diagnoses of "squamous cell carcinoma" or "non-small cell carcinoma consistent with squamous cell carcinoma" are classified as squamous cell carcinoma, whereas "adenocarcinoma," "non-small cell carcinoma consistent with adenocarcinoma," and "non-small cell carcinoma NOS" are classified as non-squamous cell carcinoma.

2. Meets one of the following criteria (1-3):

1. Stage IB-III (preoperative clinical stage) deemed resectable, with no planned neoadjuvant therapy.

2. Stage III disease deemed amenable to curative-intent chemoradiotherapy. 3. Stage II-III (preoperative clinical stage) deemed resectable, with planned neoadjuvant therapy.

3) Age ≥ 18 years at the time of enrollment. 4) The attending physician has determined that tissue and blood samples can be provided.

5) Written informed consent has been obtained from the patient.

Exclusion Criteria:

• Presence of active multiple primary malignancies (defined as synchronous multiple cancers/tumors or metachronous multiple cancers/tumors with a disease-free interval of 3 years or less). However, even if the disease-free interval is less than 3 years, a history of clinical stage I prostate cancer or a completely resected cancer with any of the pathological stages specified below is not considered "active multiple primary malignancies.

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Neoadjuvant therapy group; Resectable preoperative clinical stage II-III disease (with planned neoadjuvant therapy)
Adjuvant therapy group; Resectable preoperative clinical stage IB-III disease (with no planned neoadjuvant therapy)
Surgery-alone group; Resectable preoperative clinical stage IB-III disease (with no planned neoadjuvant therapy)
Chemoradiotherapy group; Unresectable clinical stage III disease

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
2-year PFS	Analyses are planned to be performed 4.5 years after the start of the study.

Collaborators and Investigators

• Sponsor: National Cancer Center, Japan
• Collaborators: Natera, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2025
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2029

Study Registration Dates

• First Submitted: February 25, 2025
• First Submitted That Met QC Criteria: February 25, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 25, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: NSCLC; lung cancer; minimal residual disease; MRD; Signatera™
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplastic Processes; Lung Neoplasms; Neoplasm, Residual
• Other Study ID Numbers: JCOG2111A

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes