Impact of Radiotherapy-Immunotherapy Timing in NSCLC Brain Metastases

NCT07638709 | Not Yet Recruiting DMC

• 2 other identifiers: 2026051108ZXQ2026B05
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this observational study is to learn about the effects of the timing of radiation therapy and immunotherapy in adults with non-small cell lung cancer (NSCLC) that has spread to the brain. The main questions it aims to answer are:

1. 1.Does the timing of the two treatments change how long the brain tumor stays stable and how long participants live?
2. 2.What medical problems do participants have when receiving these treatments at different times?
3. 3.How does the timing of treatments affect the body's immune system?
4. 4.Allow researchers to collect information about their treatment, health, and medical imaging during regular checkups.
5. 5.Give a small blood sample during their routine blood draws.
6. 6.Have standard magnetic resonance imaging (MRI) scans of their brain.

Conditions

Non Small Cell Lung; Brain Metastasases

Outcome Measures

Primary Outcomes (1)

• Intracranial Progression-Free Survival (iPFS)

  Defined as the time from study enrollment (or completion of baseline assessment) to the first documented intracranial disease progression according to the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria via blinded independent central review, or death from any cause.

  Up to approximately 2 years (Assessed every 2-3 months in the first year, and every 3-6 months thereafter until disease progression or death).

Secondary Outcomes (7)

• Intracranial Objective Response Rate (iORR)

  Up to approximately 2 years.

• Overall Survival (OS)

  Up to approximately 2 years.

• Duration of Response (DOR)

  Up to approximately 2 years.

• Best Overall Response (BOR)

  Up to approximately 2 years.

• Intracranial Disease Control Rate (iDCR)

  At 24 weeks

Other Outcomes (4)

• Parasagittal Dura (PSD) Volume

  Baseline and follow-up MRI assessments up to approximately 2 years.

• Meningeal Lymphatic Drainage Rate

  Baseline and follow-up MRI assessments up to approximately 2 years.

• Meningeal Lymphatic Vessel Diameter

  Baseline and follow-up MRI assessments up to approximately 2 years.

Study Arms (1)

Non-small cell lung cancer brain metastases

This cohort comprises adult patients (aged 18 years and older) with histologically or cytologically confirmed (NSCLC who have brain metastases confirmed by contrast-enhanced head MRI. Participants in this cohort are scheduled to receive standard-of-care radiotherapy combined with PD-1/PD-L1 immune checkpoint inhibitors based on real-world clinical treatment plans. Eligible participants must have an ECOG performance status of 0 to 2, an expected survival of at least 3 months, and be either driver-gene negative or have experienced disease progression following prior targeted therapies. The cohort strictly excludes patients who have a history of WBRT, SRS for brain metastases, or brain surgery. Additionally, individuals with contraindications to MRI (or intolerance to gadolinium contrast agents), active autoimmune diseases requiring systemic treatment or long-term high-dose immunosuppressants, and pregnant or lactating women are excluded.

Radiation: Brain radiotherapy

Interventions

Brain radiotherapy RADIATION

Participants in this observational study receive standard-of-care radiotherapy for brain metastases combined with PD-1/PD-L1 immune checkpoint inhibitors. The specific radiotherapy parameters (e.g., technique, target volume, and dose) and immunotherapy details (e.g., specific drug type, dosage, and administration schedule) are entirely determined by the treating physicians or multidisciplinary team (MDT) based on current clinical guidelines and real-world practice. This study does not assign, alter, or proactively intervene in any treatment plans. What distinguishes the exposure in this study is the specific tracking and categorization of the real-world timing interval and administration sequence between radiotherapy and immunotherapy (e.g., synchronous vs. asynchronous, radiation-first vs. immunotherapy-first), aiming to evaluate how these naturally occurring temporal variations impact clinical outcomes and immune status.

Non-small cell lung cancer brain metastases

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population comprises adult patients (aged 18 years and older) histologically or cytologically diagnosed with non-small cell lung cancer (NSCLC) accompanied by brain metastases, confirmed via contrast-enhanced head MRI. These patients are seeking treatment at Xiangya Hospital and are scheduled to receive a combination of radiotherapy and PD-1/PD-L1 immune checkpoint inhibitors according to their routine, real-world clinical care plans. The cohort specifically represents a real-world NSCLC population with relatively good performance status (ECOG 0-2), intact local brain anatomy (no prior history of whole-brain radiotherapy, stereotactic radiosurgery, or brain surgery), and who are negative for actionable driver mutations or have experienced disease progression following prior targeted therapies.

You may qualify if:

• Age ≥ 18 years; no gender restriction;
• Histologically or cytologically confirmed NSCLC, with brain metastases confirmed by contrast-enhanced cranial MRI;
• Scheduled to receive radiotherapy combined with a PD-1/PD-L1 inhibitor, in accordance with real-world clinical treatment plans;
• Negative for driver gene mutations, or positive for mutations but with documented failure of prior targeted therapy;
• ECOG Performance Status score of 0-2, with an estimated life expectancy of ≥ 3 months;
• Voluntarily signs the informed consent form and agrees to cooperate with blood/imaging data collection and follow-up procedures.

You may not qualify if:

• History of whole-brain radiotherapy, stereotactic radiotherapy for brain metastases, or brain surgery;
• Presence of contraindications to MRI or inability to tolerate gadolinium-based contrast agents (e.g., severe hepatic or renal insufficiency);
• Presence of active autoimmune disease requiring systemic treatment, or requirement for long-term use of high-dose immunosuppressive agents;
• Pregnant or lactating women;
• Other circumstances deemed by the investigator to involve severe complications or render the patient unsuitable for enrollment.

Sponsors & Collaborators

• Xiangya Hospital of Central South University: lead

Study Sites (1)

Xiangya Hospital of Central South University

Changsha, Hunan, China

Location

Central Study Contacts

Rongrong Zhou, MD, PHD

CONTACT

+8613875898127; zhourr@csu.edu.cn

Weihua Liao, MD, PHD

CONTACT

+8613973126486; ouwenliao@163.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 2 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Department of Oncology

Study Record Dates

• First Submitted: June 4, 2026
• First Posted: June 10, 2026
• Study Start: June 5, 2026
• Primary Completion (Estimated): May 31, 2029
• Study Completion (Estimated): June 1, 2030
• Last Updated: June 10, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)