RecruitingPhase 1NCT06431685

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


Sponsor

Sichuan University

Enrollment

10 participants

Start Date

Apr 25, 2024

Study Type

INTERVENTIONAL

Conditions

Summary

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.


Eligibility

Min Age: 18 YearsMax Age: 75 Years

Inclusion Criteria12

  • ≥ 18 years old and ≤ 75 years old;
  • 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.;
  • Patients with a clear history of lung carcinoma, including histopathological diagnosis or a combination of cytopathology and imaging, and failure of standard treatment;
  • Efficacy of extracranial lesions SD;
  • Patients with no contraindications to craniocranial radiotherapy were judged by radiotherapy doctors. Subjects who agree to receive immunotherapy, Lumbar puncture, intrathecal chemotherapy, and radiotherapy;
  • Expected survival ≥3 months, PS score ≤3;
  • Agree to provide cerebrospinal fluid, blood and tissue samples for biomarker testing;
  • The main organs function normally, no serious blood, heart, lung, liver, kidney, bone marrow and other functional abnormalities and immune deficiency diseases;
  • 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);
  • 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 Criteria9

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

Interventions

RADIATIONWhole 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).

DRUGPemetrexed

Pemetrexed, 30 mg, intrathecal injection, once per three weeks, 4 cycles in total

DRUGSintilimab

PD-1 inhibitor (Sintilimab, dose as recommended in the instruction manual), intravenous infusion, once per three weeks, 4 cycles in total

DRUGChemotherapy

Pemetrexed at a dose of 500 mg/m\^2, intravenous infusion, once per three weeks, 4 cycles in total


Locations(1)

West China Hospital, Sichuan University

Chengdu, Sichuan, China

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NCT06431685


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