Impact of Radiotherapy-Immunotherapy Timing in NSCLC Brain Metastases

ConditionsNon Small Cell Lung Brain Metastasases

Trial statusNot yet recruiting

Trial phaseNot listed

Trial typeObservational

Biological sexAll

Age18+

SponsorXiangya Hospital of Central South University

About this trial

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. Does the timing of the two treatments change how long the brain tumor stays stable and how long participants live? 2. What medical problems do participants have when receiving these treatments at different times? 3. How does the timing of treatments affect the body's immune system?

Researchers will compare participants who receive radiation and immunotherapy 30 days or less apart to those who receive them more than 30 days apart to see if the timing affects the treatment's success and safety.

Participants already receiving radiation and immunotherapy as part of their regular medical care will:

1. Allow researchers to collect information about their treatment, health, and medical imaging during regular checkups. 2. Give a small blood sample during their routine blood draws. 3. Have standard magnetic resonance imaging (MRI) scans of their brain.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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;

Disqualifiers

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;

Trial 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.

Trial design

Design model

Cohort

Time perspective

Prospective

Treatments tested in this trial

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.

Treatment groups

150 Participants

are divided into 1 treatment group

Group A: Non-small cell lung cancer brain metastases1 intervention

Trial outcomes

Primary outcomes

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.

Time frame

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

Intracranial Objective Response Rate (iORR)

The proportion of patients achieving an intracranial Complete Response (CR) or Partial Response (PR) per RANO-BM criteria. Responses must be confirmed by consecutive imaging assessments at least 4 weeks apart.

Time frame

Up to approximately 2 years.

Overall Survival (OS)

Defined as the time from study enrollment to death from any cause.

Time frame

Up to approximately 2 years.

Duration of Response (DOR)

For patients achieving confirmed CR or PR, defined as the time from the first documented objective response to the first documented disease progression or death from any cause.

Time frame

Up to approximately 2 years.

Best Overall Response (BOR)

The best disease response recorded from the start of the study treatment until disease progression or recurrence.

Time frame

Up to approximately 2 years.

Other outcomes

Parasagittal Dura (PSD) Volume

Quantitative measurement of the parasagittal dura (PSD) volume derived from contrast-enhanced 7.0T MRI. PSD volume will be calculated using standardized image segmentation and volumetric analysis procedures and reported in cubic millimeters (mm³).

Time frame

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

Meningeal Lymphatic Drainage Rate

Quantitative assessment of meningeal lymphatic drainage efficiency measured using contrast-enhanced 7.0T MRI. Drainage rate will be calculated according to predefined imaging analysis protocols and expressed as a percentage or kinetic parameter reflecting lymphatic drainage function.

Time frame

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

Meningeal Lymphatic Vessel Diameter

Mean diameter of visualized meningeal lymphatic vessels measured on contrast-enhanced 7.0T MRI using standardized image analysis methods and reported in millimeters (mm).

Time frame

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

Deep Cervical Lymph Node (dCLN) Inflow Rate

Quantitative assessment of contrast agent inflow into deep cervical lymph nodes measured using contrast-enhanced 7.0T MRI. The inflow rate will be used as an indicator of meningeal lymphatic drainage function.

Time frame

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

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Xiangya Hospital of Central South University

Lead sponsor

Source ClinicalTrials.gov

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