Consolidative Stereotactic Radiotherapy for Oligo-Residual Advanced EGFR-Mutant NSCLC After First-Line Third-Generation EGFR-TKI Plus Chemotherapy

September 10, 2026 updated by: Zhengfei Zhu, Fudan University

Consolidative Stereotactic Radiotherapy for Oligo-Residual Advanced EGFR-Mutant Non-Small Cell Lung Cancer After First-Line Treatment With Third-Generation EGFR Tyrosine Kinase Inhibitor Plus Chemotherapy: A National Multicenter, Randomized Controlled Clinical Trial

This national multicenter, randomized controlled clinical trial evaluates the safety and efficacy of consolidative stereotactic radiotherapy in patients with advanced EGFR-mutant non-small cell lung cancer who have oligo-residual disease after four cycles of first-line treatment with third-generation EGFR-TKI plus platinum-based pemetrexed chemotherapy. Eligible participants will be randomized 1:1 to continue third-generation EGFR-TKI plus pemetrexed maintenance therapy alone or to receive stereotactic radiotherapy to all oligo-residual lesions in addition to the same maintenance therapy. The primary endpoint is progression-free survival.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

374

Phase

  • Phase 2

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Histologically confirmed non-small cell lung cancer.
  • Clinical stage IV disease according to the AJCC 9th edition.
  • Sensitizing EGFR mutation: EGFR exon 19 deletion or EGFR L858R.
  • Age 18-75 years.
  • Karnofsky Performance Status score ≥70.
  • Complete whole-body imaging assessment before initiation of first-line third-generation EGFR-TKI plus chemotherapy, with at least one evaluable lesion according to RECIST version 1.1.
  • No disease progression after completion of four cycles of first-line third-generation EGFR-TKI plus chemotherapy and no unresolved grade ≥3 nonhematologic toxicity.
  • Oligo-residual disease after four treatment cycles, with all residual lesions considered suitable for stereotactic radiotherapy by the investigator.
  • Written informed consent.

Exclusion Criteria:

  • Double primary or multiple primary malignancies, except early skin cancer or cervical carcinoma in situ treated with curative intent and without recurrence or progression for at least five years.
  • Pregnancy or breastfeeding, or considered unsuitable by the investigator for PET/CT or brain MRI examination.
  • History of uncontrolled epilepsy, central nervous system disease, or psychiatric disorder that, in the investigator's judgment, may interfere with informed consent or participant compliance.
  • Residual lesions considered unsuitable for consolidative stereotactic radiotherapy after first-line third-generation EGFR-TKI plus chemotherapy.

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: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Radiotherapy plus TKI Group
Consolidative stereotactic radiotherapy plus continued third-generation EGFR-TKI and pemetrexed maintenance therapy.
Drug: Third-generation EGFR tyrosine kinase inhibitor
administered during induction and maintenance; the specific third-generation EGFR-TKI is not uniformly restricted in the protocol.
Drug: Platinum plus pemetrexed chemotherapy
cisplatin or carboplatin plus pemetrexed for four 3-week cycles during induction.
Drug: Pemetrexed maintenance therapy
administered with the third-generation EGFR-TKI until disease progression or unacceptable toxicity.
Radiation: Consolidative stereotactic radiotherapy
SRS/SRT/SBRT delivered to all eligible intracranial and/or extracranial oligo-residual lesions, completed as a single course or in staged courses within one month.
Active Comparator: TKI alone Group
Continued third-generation EGFR-TKI and pemetrexed maintenance therapy alone.
Drug: Third-generation EGFR tyrosine kinase inhibitor
administered during induction and maintenance; the specific third-generation EGFR-TKI is not uniformly restricted in the protocol.
Drug: Platinum plus pemetrexed chemotherapy
cisplatin or carboplatin plus pemetrexed for four 3-week cycles during induction.
Drug: Pemetrexed maintenance therapy
administered with the third-generation EGFR-TKI until disease progression or unacceptable toxicity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-Free Survival (PFS)
Time Frame: 4 years
The time from randomization to disease progression or death of the patient. Patients who have not yet progressed at the time of analysis will be censored at the date of their last contact.
4 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: 4 years
4 years
Intracranial Progression-Free Survival (iPFS)
Time Frame: 4 years
4 years
Health-Related Quality of Life (HRQoL)
Time Frame: 4 years
health-related quality of life assessed using the QLQ-C30 and QLQ-LC13 questionnaires
4 years
Incidence of Treatment-Related Toxicities
Time Frame: 4 years
proportion of evaluable participants experiencing treatment-related toxicities, graded according to CTCAE version
4 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
peripheral blood specimens
Time Frame: 4 years
This study requires that peripheral blood specimens be collected as much as possible at the time points specified in the study, and that they be stored and processed in accordance with standard procedures, in order to explore the clinical value of liquid biopsy for oligo-residual disease prediction, early warning of drug resistance, and prognostic assessment.
4 years

Collaborators and Investigators

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

Sponsor

Fudan University

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 (Estimated)

October 1, 2026

Primary Completion (Estimated)

September 1, 2030

Study Completion (Estimated)

September 1, 2030

Study Registration Dates

First Submitted

August 7, 2026

First Submitted That Met QC Criteria

September 10, 2026

First Posted (Actual)

September 16, 2026

Study Record Updates

Last Update Posted (Actual)

September 16, 2026

Last Update Submitted That Met QC Criteria

September 10, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LUNG-SORT2

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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