Immune Checkpoint Inhibitors Intrathecal Injection in Patients With Leptomeningeal Metastases in NSCLC

Study Purpose

This is a prospective, single-arm, open clinical study, which was designed to evaluate the efficacy and safety of an immune checkpoint inhibitor combined with pemetrexed intrathecal injection in the treatment of patients with NSCLC associated with leptomeningeal metastases.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

Yes
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years - 75 Years
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

1. Aged 18-75 years old, male or female; 2. Patients with pathologically diagnosed non-small cell lung cancer with cerebrospinal fluid and/or MRI diagnosis of leptomeningeal metastasis; 3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2; 4. Expected survival time of at least 4 weeks; 5. Oncologist clarification of the potential necessity of receiving systemic therapy for metastatic tumors outside the CNS; 6. Previous radiation therapy, including whole brain radiation, stereotactic radiosurgery, or stereotactic body radiation therapy (SBRT), which must be completed at least 7 days prior to the start of treatment; 7. Patients who have received approved targeted therapies (EGFR inhibitors, ALK inhibitors, or other targeted therapeutic agents), and other systemic therapies will be allowed to remain on concurrent therapy; concurrent intrathecal therapy with other agents will not be allowed. 8. Laboratory test indicators meet the following criteria: 1. Bone marrow function: hemoglobin (Hb) ≥80g/L; white blood cell count (WBC) ≥lower limit of normal; absolute neutrophil count (ANC) ≥1.5×10^9 /L; platelet count ≥70×109 /L; 2. Renal function: Cr ≤ ULN (upper limit of normal) × 1.5, endogenous creatinine clearance (Ccr) ≥ 55 ml/min; 3. Liver function: total bilirubin ≤ ULN × 1.5; ALT and AST ≤ ULN × 2.5; (if there is liver metastasis, total bilirubin is not higher than 3 times the upper limit of normal, and transaminases are not higher than 5 times the upper limit of normal); 4. Coagulation function: international normalized ratio of prothrombin time ≤ ULN × 1.5, and partial thromboplastin time within the normal value; 9. Females of child-bearing potential agree to use contraception during the study period and for 6 months after the completion of the study; patients who have had a negative serum or urine pregnancy test within seven days prior to enrollment in the study and who are not breastfeeding; and males agreeing to use contraception during the study period and for 6 months after the completion of the study; 10. Those who have not participated in another drug clinical trial within 4 weeks prior to enrollment; 11. Subjects who can understand the study situation and voluntarily sign the informed consent form; 12. Patients are expected to be compliant and able to follow up on efficacy and adverse events according to protocol requirements.

Exclusion Criteria:

1. Diagnosis of other malignant tumors (except carcinoma in situ, basal cell carcinoma, etc.) within the previous 5 years; 2. History of allergy to pemetrexed and ICIs therapy; 3. Any previous intrathecal injection therapy; 4. Rule out differential diagnosis of LM:a. Aseptic meningitis b. Viral meningitis c. Bacterial meningitis; 5. Participation in other clinical trials or observation periods; 6. Clinical conditions that would interfere with the evaluation or interpretation of safety or findings, or impede the understanding of informed consent and compliance with protocol requirements; 7. Presence of any treatment-related toxicity from prior systemic antitumor therapy other than alopecia that does not meet CTCAE grade 1 (based on CTCAE 5.0); 8. Presence of any active autoimmune disease or history of autoimmune disease; immunodeficiency, active tuberculosis, hepatitis B ( hepatitis B virus titer HBV-DNA <500 IU/ml after treatment and if liver function is normal will be allowed), or positive test for hepatitis C virus. 9. Either disease resulting in permanent immunosuppression or requiring permanent immunosuppressive therapy; 10. Presence of active infection or serious comorbidities; 11. uncontrolled epilepsy, neurologic failure, or severe neurologic impairment related to treatment; 12. Presence of hereditary or acquired bleeding and thrombotic tendencies; 13. History of severe injury or surgery within 1 month prior to enrollment; 14. Treatment with a live or attenuated vaccine used for the prevention of infectious diseases within 30 days prior to the first administration (injectable seasonal influenza vaccine is permitted); 15. Inability to complete an enhanced MRI; 16. Treatment with immunosuppressive drugs or corticosteroids (> 10 mg prednisone or equivalent per day) within 14 days prior to enrollment; patients are allowed to receive steroid therapy to control CNS-related symptoms, but the dose must ≤ 5 mg per day of dexamethasone (or equivalent); in the absence of an active autoimmune disease, inhaled or topical steroids and adrenal gland replacement dosing are acceptable; alternative therapies (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) are permitted; patients with experimental medications that require premedication with corticosteroids are not restricted; 17. Individuals considered by the investigator to be unsuitable for enrollment.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT06132698
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

West China Hospital
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

N/A
Principal Investigator Affiliation N/A
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Not yet recruiting
Countries
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

NSCLC Associated With Leptomeningeal Metastases
Arms & Interventions

Arms

Experimental: Enrolled patients were treated with an immune checkpoint inhibitor combined with pemetrexed intrathe

Interventions

Drug: - Tislelizumab, pemetrexed

Drug 1: Tislelizumab 50 mg; Drug 2: pemetrexed 20mg. intrathecal injection therapy

Contact Information

This trial has no sites locations listed at this time. If you are interested in learning more, you can contact the trial's primary contact:

For additional contact information, you can also visit the trial on clinicaltrials.gov.

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