Trial Title:
Safety and Efficacy of Whole Brain LDRT+ICI+Intrathecal Chemotherapy in Refractory Meningeal Metastasis of Lung Cancer
NCT ID:
NCT06431685
Condition:
NSCLC
Low Dose Radiotherapy
PD-1 Inhibitor
Leptomeningeal Metastasis
Conditions: Official terms:
Neoplasm Metastasis
Pemetrexed
Immune Checkpoint Inhibitors
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Radiation
Intervention name:
Whole Brain Low Dose Radiotherapy
Description:
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).
Arm group label:
whole brain LDRT + ICI + intrathecal chemotherapy
Other name:
WB-LDRT
Intervention type:
Drug
Intervention name:
Pemetrexed
Description:
Pemetrexed, 30 mg, intrathecal injection, once per three weeks, 4 cycles in total
Arm group label:
whole brain LDRT + ICI + intrathecal chemotherapy
Other name:
Intrathecal Chemotherapy
Intervention type:
Drug
Intervention name:
Sintilimab
Description:
PD-1 inhibitor (Sintilimab, dose as recommended in the instruction manual), intravenous
infusion, once per three weeks, 4 cycles in total
Arm group label:
whole brain LDRT + ICI + intrathecal chemotherapy
Other name:
PD-1 Inhibitor
Intervention type:
Drug
Intervention name:
Chemotherapy
Description:
Pemetrexed at a dose of 500 mg/m^2, intravenous infusion, once per three weeks, 4 cycles
in total
Arm group label:
whole brain LDRT + ICI + intrathecal chemotherapy
Other name:
One of the standard chemotherapy regimens
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.
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.
Criteria for 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
West China Hospital, Sichuan University
Address:
City:
Chengdu
Zip:
610041
Country:
China
Status:
Recruiting
Contact:
Last name:
Lisha Xiang, MD
Phone:
13320943069
Phone ext:
+86
Email:
lishaxiang@foxmail.com
Start date:
April 25, 2024
Completion date:
December 2026
Lead sponsor:
Agency:
Sichuan University
Agency class:
Other
Source:
Sichuan University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06431685
