Phase III, Multicenter, Randomized Controlled Clinical Study of Three-Dimensional Radiotherapy for Primary Tumors in Non-Oligometastatic Stage IV Non-Small Cell Lung Cancer

For patients with non-small cell lung cancer and more than five metastatic lesions (non-oligometastatic disease), does radical treatment of the primary lung lesion, in addition to pharmacotherapy, also provide benefits in terms of progression-free survival (PFS) and local control? Currently, there is limited clinical research on combining pharmacotherapy with radiotherapy for the primary lesion in non-oligometastatic patients. Therefore, this study aims to investigate whether radical radiotherapy targeting the primary lung lesion, in addition to pharmacotherapy, can improve local control and survival in non-oligometastatic patients, and whether the associated toxicities are acceptable.

Study Overview

• Status: Not yet recruiting
• Conditions: Non Small Cell Lung Cancer Metastatic; Radiotherapy
• Intervention / Treatment: Radiation: Three-Dimensional Radiotherapy for Primary lungTumors

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Bing Lu; Phone Number: +86 13809432527; Email: lbgymaaaa@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Pathologically or cytologically confirmed stage IV NSCLC [9th edition, 2024];
2. Non-oligometastatic disease (number of metastatic lesions > 5, regardless of the number of organs involved); patients with brain metastases must be conscious; the number of lung metastases must not affect lung function and allow for possible primary tumor radiotherapy;
3. Treatment-naïve (no prior antitumor therapy); or disease control after 1-3 months of monotherapy with TKI, ALK inhibitor/ROS inhibitor; or disease control after 4-6 cycles of chemotherapy combined with immunotherapy;
4. Age 18-80 years, ECOG 0-2 or KPS ≥70; no contraindications to radiotherapy, EGFR-TKI, ALK/ROS1 inhibitors, chemotherapy, or immunotherapy;
5. No major organ dysfunction, or laboratory test results must meet the following criteria: Hematology , cardiac function, liver function , and renal function within normal ranges according to respective laboratory standards. Pulmonary function : FEV1 >50%, mild to moderate impairment of lung function.
6. Signed informed consent before treatment (for radiotherapy, chemotherapy, immunotherapy, and targeted drug therapy);
7. Good patient compliance with the treatment and follow-up.

Exclusion Criteria:

1. Stage I-III NSCLC, oligometastasis (number of metastatic lesions ≤ 5), Stage IV NSCLC with malignant serous cavity effusion, or KPS ≤ 60;
2. Patients with extensive liver metastases or lung metastases that have severely impaired liver or lung function;
3. Patients with uncontrolled hypertension, diabetes, unstable angina, history of myocardial infarction, symptomatic congestive heart failure within the past 12 months, or uncontrolled arrhythmia; clinically diagnosed valvular heart disease; active bacterial, fungal, or viral infections; mental disorders; severe pulmonary dysfunction;
4. Pregnant or lactating patients;
5. Patients with a history of other active malignant tumors prior to enrollment, except for non-small cell lung cancer; excluding non-melanoma skin basal cell carcinoma, cervical carcinoma in situ, and cured early-stage prostate cancer;
6. Patients with allergic constitution or known/suspected allergy to any investigational drugs without alternative medications;
7. Patients with poor compliance; Patients deemed unsuitable for participation in this trial by the investigator.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Pharmacotherapy group; For patients positive for driver gene mutations, first-line targeted therapy with or without chemotherapy is recommended according to NCCN guidelines. For patients negative for driver gene mutations, first-line immunotherapy combined with chemotherapy is recommended according to NCCN guidelines.
Experimental: Radiotherapy group; For patients positive for driver gene mutations, first-line targeted therapy with or without chemotherapy is recommended according to NCCN guidelines. For patients negative for driver gene mutations, first-line immunotherapy combined with chemotherapy is recommended according to NCCN guidelines. Concurrent radiotherapy for the primary tumor in combination with drug therapy.	Radiation: Three-Dimensional Radiotherapy for Primary lungTumors; The experimental group received radical radiotherapy for the primary lung lesion in combination with first-line drug therapy recommended by the NCCN guidelines.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival, Local regional progressive-free survival, LRPFS	OS refers to the period the date of randomization in a clinical trial until the patient dies from any cause. Local progression-free survival time refers to the duration from randomization until the first occurrence of local progression at the primary tumor site or region, or death from any cause	From enrollment to the end of treatment at 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR,	ORR define the objective response rate according to RECIST version 1.1.	From enrollment to the end of treatment at 1year.
PFS	PFS, definehe length of time during and after treatment that a patient lives with the disease but it does not get worse. It is typically measured from the start of treatment until disease progression or death from any cause.	From enrollment to the end of treatment at 1 year
Toxicities	Toxicities: The primary assessment of radiotherapy-related toxicities is based on the CTC 5.0 criteria, focusing on treatment-related toxicities such as radiation pneumonitis, radiation esophagitis, bone marrow suppression, and hematologic toxicities affecting the liver and kidneys. And the time without cancer worsening or death	From enrollment to the end of treatment at 1 year

Collaborators and Investigators

• Sponsor: Guizhou Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): March 30, 2026
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2027

Study Registration Dates

• First Submitted: February 1, 2026
• First Submitted That Met QC Criteria: March 8, 2026
• First Posted (Actual): March 10, 2026

Study Record Updates

• Last Update Posted (Actual): March 10, 2026
• Last Update Submitted That Met QC Criteria: March 8, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: non-oligometastatic NSCLC; radical radiotherapy of the primary lung lesion; pharmacotherapy with radiotherapy for the primary lesion
• Other Study ID Numbers: FZ 2025-09-246

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