Combining low dose brain radiotherapy with immunotherapy and intrathecal chemotherapy for lung cancer

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 study is testing a new treatment that combines low dose brain radiation, immune therapy, and chemotherapy to see if it helps people with tough lung cancer that has spread to the brain.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Sichuan University (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 1 site (Chengdu, Sichuan)
• Trial ID: NCT06431685 on ClinicalTrials.gov

What this trial studies

This phase I study investigates the safety and efficacy of whole brain low dose radiotherapy (WB-LDRT) combined with immune checkpoint inhibitors (ICI) and intrathecal chemotherapy in patients with refractory meningeal metastasis from lung cancer. The study will enroll three cohorts of patients, each receiving different cycles of WB-LDRT alongside pemetrexed chemotherapy and a PD-1 inhibitor. Participants will be monitored for safety and treatment response, with the goal of determining the optimal treatment regimen for this challenging condition.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with a confirmed diagnosis of leptomeningeal metastasis from lung cancer who have failed standard treatments.

Not a fit: Patients with contraindications to craniocranial radiotherapy or those with severe organ dysfunction may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a new treatment option for patients with refractory meningeal metastasis of lung cancer, potentially improving survival and quality of life.

How similar studies have performed: While this approach is exploratory, similar combinations of radiotherapy and immunotherapy have shown promise in other cancer types, suggesting potential for success.

Eligibility criteria

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.

Where this trial is running

Chengdu, Sichuan

• West China Hospital, Sichuan University — Chengdu, Sichuan, China (Recruiting)

Study contacts

• Principal investigator: You Lu, MD — West China Hospital
• Study coordinator: You Lu, MD

Conditions NSCLC; Low Dose Radiotherapy; PD-1 Inhibitor; Leptomeningeal Metastasis