SRT for Residual Oligometastases of NSCLC After 3rd Generation EGFR-TKIs

An Open-label, Single-Arm, Phase 2 Trial of Stereotactic Radiotherapy for Patients With Residual Oligometastases of NSCLC After 3rd Generation EGFR-TKIs

This study is an open-label, single-arm phase 2 trial to evaluate the efficacy and safety of stereotactic radiotherapy (SRT) for patients with oligo-residual NSCLC after 3rd generation EGFR-TKIs.

Study Overview

• Status: Completed
• Conditions: NSCLC Stage IV; EGFR Activating Mutation
• Intervention / Treatment: Drug: 3rd generation EGFR-TKI; Radiation: Consolidative SRT

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • Fudan University Shanghai Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• The patient has a diagnosis of pathologically confirmed NSCLC by tumor biopsy and/or fine-needle aspiration.
• The patient has a diagnosis of American Joint Committee on Cancer (AJCC) 8th Edition stage IV NSCLC.
• The patient receives 3rd generation EGFR-TKI in the first line setting.
• The patient is ≥18 years of age and ≤75 years of age at the time of screening.
• The patient's Karnofsky performance score (KPS) is ≥70 at study entry.
• The patient has adequate baseline tumor assessment before initiation of 3rd generation EGFR-TKI.
• The patient has at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.
• The patient presents with a residual "oligometastatic" state after 3rd generation EGFR-TKI therapy that would be amenable to consolidative SRT in the opinion of the investigator.
• The patient has signed informed consent.
• EGFR Exon19 deletion or Exon21 L858R mutation

Exclusion Criteria:

• History of another malignancy or concurrent malignancy. Patients with cervical carcinoma in situ or adequately treated basal cell carcinoma who have been disease free for > 5 years are eligible.
• The patient is pregnant (confirmed by serum b-HCG if applicable) or is breastfeeding.
• Patients with uncontrolled epilepsy, mental disorders, drug abuse, or social condition that may affect compliance or ability to sign a written informed consent in the opinion of the investigator.
• Patients with residual metastatic disease after 3rd generation EGFR-TKI therapy that is deemed not amenable to consolidative SRT.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 3rd generation EGFR-TKI+ SRT; Patients were treated with the intent to ablate all residual disease with consolidative SRT. EGFR-TKI treatment was continued during and after consolidative SRT until disease progression or intolerable toxicity.

Drug: 3rd generation EGFR-TKI; Osimertinib will be administered orally at the dose of 80 mg once daily.; Other Names: Osimertinib; Radiation: Consolidative SRT; Patients who possess oligoresidual disease after 3rd generation EGFR-TKI therapy will be treated with the intent to ablate all residual disease with consolidative SRT. The choice of dose-fractionation regimen is at the discretion of the treating radiation oncologist. TKI will be continued during and after consolidative SRT until disease progression or intolerable toxicity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	PFS was measured from the date of enrollment to the date of disease progression as defined by Response Evaluation Criteria in Solid Tumor (RECIST) Version 1.1 or death due to any cause, whichever occurred first. For patients whose disease did not progress, PFS was evaluated by censoring patients at their most recent imaging.	Two years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Adverse Events	Treatment-related adverse events were assessed and graded according to CTCAE v. 5.0.	Two years
Overall Survival	OS was defined as the time from the date of enrollment until death by any cause. Participants still alive at the time of data analysis were censored at the date of last follow-up.	Two years

Collaborators and Investigators

• Sponsor: Fudan University
• Investigators: Principal Investigator: Zhengfei Zhu, MD, Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Actual): March 31, 2023
• Study Completion (Actual): July 20, 2023

Study Registration Dates

• First Submitted: February 19, 2021
• First Submitted That Met QC Criteria: February 19, 2021
• First Posted (Actual): February 21, 2021

Study Record Updates

• Last Update Posted (Actual): August 19, 2024
• Last Update Submitted That Met QC Criteria: August 16, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Tyrosine Kinase Inhibitors; Osimertinib
• Other Study ID Numbers: 2020-NSCLCSBRT-1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No