Safety and Efficacy of Whole Brain LDRT+ICI+Intrathecal Chemotherapy in Refractory Meningeal Metastasis of Lung Cancer

May 4, 2026 updated by: You Lu, Sichuan University

Phase I Study of Whole Brain Low Dose Radiotherapy Combined With ICI and Intrathecal Chemotherapy for Treatment of Refractory Meningeal Metastasis of Lung Cancer

This phase I study aims to investigate the safety and efficacy of whole brain low dose radiotherapy (WB-LDRT) combined with ICI and intrathecal chemotherapy for treatment of refractory meningeal metastasis of lung cancer.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This exploratory phase I study will be conducted in West China Hospital, Sichuan University. Three cohorts of whole brain low dose radiotherapy (3 patients per cohort) will be enrolled to determine the safety and efficacy of whole brain low dose radiotherapy combined with ICI and intrathecal chemotherapy for treatment of refractory meningeal metastasis of lung cancer.

Subjects who fulfil all the inclusion criteria and none of the exclusion criteria will be enrolled and receive treatment with WB-LDRT at same dose (4 Gy/2f) with diffent cycles (decried as below), PD-1 inhibitor, pemetrexed chemotherapy, and intrathecal pemetrexed every 3 weeks (Q3w) for 4 cycles.

Patients will receive WB-LDRT at 3 cohorts with increasing dose fractions: 4 Gy/2f of one cycle in group 1; 4 Gy/2f of two cycles in group 2; 4 Gy/2f of four cycles in group 3.

Study Type

Interventional

Enrollment (Estimated)

10

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Sichuan
      • Chengdu, Sichuan, China, 610041
        • Recruiting
        • West China Hospital, Sichuan University
        • Contact:

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:

  1. ≥ 18 years old and ≤ 75 years old;
  2. Patients with a definite diagnosis of leptomeningeal metastasis by cerebrospinal fluid cytology, or patients with clinical diagnosis combined with tumor history, neuroimaging, clinical manifestations, cerebrospinal fluid examination, etc.;
  3. Patients with a clear history of lung carcinoma, including histopathological diagnosis or a combination of cytopathology and imaging, and failure of standard treatment;
  4. Efficacy of extracranial lesions SD;
  5. Patients with no contraindications to craniocranial radiotherapy were judged by radiotherapy doctors. Subjects who agree to receive immunotherapy, Lumbar puncture, intrathecal chemotherapy, and radiotherapy;
  6. Expected survival ≥3 months, PS score ≤3;
  7. Agree to provide cerebrospinal fluid, blood and tissue samples for biomarker testing;
  8. The main organs function normally, no serious blood, heart, lung, liver, kidney, bone marrow and other functional abnormalities and immune deficiency diseases;

  9. One week before enrollment, bone marrow and liver and kidney function met the following criteria:

    ① Hemoglobin ≥80 g/L, neutrophils ≥1.5×10^9/L and platelets ≥70×10^9/L;

    ② Renal function: Cr≤ULN (upper limit of normal) × 1.5, endogenous creatinine clearance (Ccr)≥55 ml/min; Liver function: total bilirubin ≤ULN × 1.5; ALT, AST≤ULN × 2.5; (In case of liver metastasis, total bilirubin should not be higher than 3 times the upper normal limit, and transaminase should not be higher than 5 times the upper normal limit);

  10. The fertile women agreed to use contraception during the study period and for 6 months after the study ended; Patients who tested negative for a serum or urine pregnancy test within 7 days prior to joining the study and were not breastfed; Men who agreed to use contraception during the study period and for 6 months after the study ended

Exclusion Criteria:

  1. Active autoimmune disease or history of autoimmune diseases;
  2. Congenital or acquired immunodeficiency;
  3. Uncontrolled cardiac clinical symptoms or diseases;
  4. Severe infection or severe comorbidities, such as bleeding peptic ulcer, ileus, heart failure, renal failure, or poorly controlled diabetes;
  5. History of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation;
  6. Other systemic malignancies within the last 5 years;
  7. Allergy to any test drug;
  8. Uncontrolled epilepsy, neurological failure, or severe treatment-related neurological impairment, uncontrollable psychosis, and other conditions deemed unsuitable for inclusion by the investigator;
  9. Pregnant and lactating women, subjects with reproductive capacity are unwilling to take effective contraceptive measures.

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: whole brain LDRT + ICI + intrathecal chemotherapy
The treatment regimen consisted of intrathecal chemotherapy (via lumbar puncture, pemetrexed 30 mg, once per three weeks, 4 cycles in total), PD-1 inhibitor (Sintilimab, via intravenous infusion, once per three weeks, 4 cycles in total)), pemetrexed chemotherapy (via intravenous infusion, once per three weeks, 4 cycles in total) and radiotherapy. Whole brain LDRT will be administered at 3 cohorts with increasing dose fractions: 4 Gy/2f of 2 fraction (administered a daily dose of 2 Gy for two days) in group 1; 4 Gy/2f of 4 fractions (administered a daily dose of 2 Gy for two days, once per three weeks, 2 cycles in total) in group 2; 4 Gy/2f of 8 fractions (administered a daily dose of 2 Gy for two days, once per three weeks, 4 cycles in total) in group 3.
Radiation: Whole Brain Low Dose Radiotherapy
Whole brain LDRT will be administered at 3 cohorts with increasing dose fractions: Group 1: 4 Gy/2f of one cycle; Group 2: 4 Gy/2f of two cycles (Q3w); Group 3: 4 Gy/2f of three cycles (Q3w). WB-LDRT will be administered in a 4 Gy of 2 fractions over two days, starting from Day 1 in the first cycle (a daily dose of 2 Gy, 4 Gy/2f for one cycle, once per three weeks, at minmum in one cycle and maximum in four cycles in total).
Other Names:
  • WB-LDRT
Drug: Pemetrexed
Pemetrexed, 30 mg, intrathecal injection, once per three weeks, 4 cycles in total
Other Names:
  • Intrathecal Chemotherapy
Drug: Sintilimab
PD-1 inhibitor (Sintilimab, dose as recommended in the instruction manual), intravenous infusion, once per three weeks, 4 cycles in total
Other Names:
  • PD-1 Inhibitor
Drug: Chemotherapy
Pemetrexed at a dose of 500 mg/m^2, intravenous infusion, once per three weeks, 4 cycles in total
Other Names:
  • One of the standard chemotherapy regimens

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical response rate
Time Frame: 48 months
The RANO proposal for response criteria of leptomeningeal metastasis was used to assess the clinical response in this study.
48 months
Incidence of treatment-related adverse events
Time Frame: 48 months
The incidence of treatment-related adverse events were measured for determing tolerability and safety. Adverse events (AEs) are evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE, version 5.0). Events of grade 3-5 are defined as moderate and severe adverse events.
48 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Neurological progression-free survival (NPFS)
Time Frame: 48 months
NPFS was defined as time from the start of treatment until neurological progression or death. The neurological progression was determined based on the RANO proposal evaluation criteria which have been established and published on Neuro Oncol.
48 months
Overall survival
Time Frame: 48 months
Survival time was recorded since the date of patient enrollment. All patients were followed up until death or the end of the study.
48 months

Collaborators and Investigators

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

Sponsor

Sichuan University

Investigators

  • Principal Investigator: You Lu, MD, West China Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 (Actual)

April 25, 2024

Primary Completion (Actual)

March 28, 2025

Study Completion (Estimated)

December 31, 2026

Study Registration Dates

First Submitted

May 19, 2024

First Submitted That Met QC Criteria

May 27, 2024

First Posted (Actual)

May 28, 2024

Study Record Updates

Last Update Posted (Actual)

May 8, 2026

Last Update Submitted That Met QC Criteria

May 4, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LM-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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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