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.
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
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
10
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).
Pemetrexed, 30 mg, intrathecal injection, once per three weeks, 4 cycles in total
PD-1 inhibitor (Sintilimab, dose as recommended in the instruction manual), intravenous infusion, once per three weeks, 4 cycles in total
West China Hospital, Sichuan University
Chengdu, Sichuan, China
RECRUITINGClinical response rate
The RANO proposal for response criteria of leptomeningeal metastasis was used to assess the clinical response in this study.
Time frame: 48 months
Incidence of treatment-related adverse events
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.
Time frame: 48 months
Neurological progression-free survival (NPFS)
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.
Time frame: 48 months
Overall survival
Survival time was recorded since the date of patient enrollment. All patients were followed up until death or the end of the study.
Time frame: 48 months
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Pemetrexed at a dose of 500 mg/m\^2, intravenous infusion, once per three weeks, 4 cycles in total