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

NCT ID: NCT06431685

Last Updated: 2024-05-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

10 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-04-25

Study Completion Date

2026-12-31

Brief Summary

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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

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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.

Conditions

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NSCLC Low Dose Radiotherapy PD-1 Inhibitor Leptomeningeal Metastasis

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Whole Brain Low Dose Radiotherapy

Intervention Type RADIATION

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

Intervention Type DRUG

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

Sintilimab

Intervention Type DRUG

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

Chemotherapy

Intervention Type DRUG

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

Interventions

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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).

Intervention Type RADIATION

Pemetrexed

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

Intervention Type DRUG

Sintilimab

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

Intervention Type DRUG

Chemotherapy

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

Intervention Type DRUG

Other Intervention Names

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WB-LDRT Intrathecal Chemotherapy PD-1 Inhibitor One of the standard chemotherapy regimens

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sichuan University

OTHER

Sponsor Role lead

Responsible Party

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You Lu

Chair of Department of Thoracic Cancer

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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You Lu, MD

Role: PRINCIPAL_INVESTIGATOR

West China Hospital

Locations

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West China Hospital, Sichuan University

Chengdu, Sichuan, China

Site Status RECRUITING

Countries

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China

Central Contacts

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You Lu, MD

Role: CONTACT

18980601763 ext. +86

Lisha Xiang, MD

Role: CONTACT

13320943069 ext. +86

Facility Contacts

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Lisha Xiang, MD

Role: primary

13320943069 ext. +86

References

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Cao M, Chen W. Epidemiology of lung cancer in China. Thorac Cancer. 2019 Jan;10(1):3-7. doi: 10.1111/1759-7714.12916. Epub 2018 Nov 28.

Reference Type BACKGROUND
PMID: 30485694 (View on PubMed)

Clarke JL, Perez HR, Jacks LM, Panageas KS, Deangelis LM. Leptomeningeal metastases in the MRI era. Neurology. 2010 May 4;74(18):1449-54. doi: 10.1212/WNL.0b013e3181dc1a69.

Reference Type BACKGROUND
PMID: 20439847 (View on PubMed)

Remon J, Le Rhun E, Besse B. Leptomeningeal carcinomatosis in non-small cell lung cancer patients: A continuing challenge in the personalized treatment era. Cancer Treat Rev. 2017 Feb;53:128-137. doi: 10.1016/j.ctrv.2016.12.006. Epub 2016 Dec 30.

Reference Type BACKGROUND
PMID: 28110254 (View on PubMed)

Gleissner B, Chamberlain MC. Neoplastic meningitis. Lancet Neurol. 2006 May;5(5):443-52. doi: 10.1016/S1474-4422(06)70443-4.

Reference Type BACKGROUND
PMID: 16632315 (View on PubMed)

Cheng H, Perez-Soler R. Leptomeningeal metastases in non-small-cell lung cancer. Lancet Oncol. 2018 Jan;19(1):e43-e55. doi: 10.1016/S1470-2045(17)30689-7.

Reference Type BACKGROUND
PMID: 29304362 (View on PubMed)

Le Rhun E, Weller M, van den Bent M, Brandsma D, Furtner J, Ruda R, Schadendorf D, Seoane J, Tonn JC, Wesseling P, Wick W, Minniti G, Peters S, Curigliano G, Preusser M; EANO Guidelines Committee and ESMO Guidelines Committee. Electronic address: [email protected]. Leptomeningeal metastasis from solid tumours: EANO-ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. ESMO Open. 2023 Oct;8(5):101624. doi: 10.1016/j.esmoop.2023.101624. Epub 2023 Sep 19.

Reference Type BACKGROUND
PMID: 37863528 (View on PubMed)

Chamberlain M, Junck L, Brandsma D, Soffietti R, Ruda R, Raizer J, Boogerd W, Taillibert S, Groves MD, Le Rhun E, Walker J, van den Bent M, Wen PY, Jaeckle KA. Leptomeningeal metastases: a RANO proposal for response criteria. Neuro Oncol. 2017 Apr 1;19(4):484-492. doi: 10.1093/neuonc/now183.

Reference Type BACKGROUND
PMID: 28039364 (View on PubMed)

Yin K, Li YS, Zheng MM, Jiang BY, Li WF, Yang JJ, Tu HY, Zhou Q, Zhong WZ, Yang XN, Chen HJ, Yan HH, Li LL, Wu YL, Zhang XC. A molecular graded prognostic assessment (molGPA) model specific for estimating survival in lung cancer patients with leptomeningeal metastases. Lung Cancer. 2019 May;131:134-138. doi: 10.1016/j.lungcan.2019.03.015. Epub 2019 Mar 18.

Reference Type BACKGROUND
PMID: 31027690 (View on PubMed)

Wang Y, Yang X, Li NJ, Xue JX. Leptomeningeal metastases in non-small cell lung cancer: Diagnosis and treatment. Lung Cancer. 2022 Dec;174:1-13. doi: 10.1016/j.lungcan.2022.09.013. Epub 2022 Oct 1.

Reference Type BACKGROUND
PMID: 36206679 (View on PubMed)

Thai K, Prat A. CNS therapeutics: Immune cells break the barriers. Sci Transl Med. 2023 Nov 8;15(721):eadh1150. doi: 10.1126/scitranslmed.adh1150. Epub 2023 Nov 8.

Reference Type BACKGROUND
PMID: 37939159 (View on PubMed)

Other Identifiers

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LM-001

Identifier Type: -

Identifier Source: org_study_id

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