- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06132698
Immune Checkpoint Inhibitors Intrathecal Injection in Patients With Leptomeningeal Metastases in NSCLC
November 14, 2023 updated by: Ting Liu, West China Hospital
Efficacy and Safety of Immune Checkpoint (PD-1) Inhibitor Combined With Pemetrexed Intrathecal Injection in Patients With Leptomeningeal Metastases in NSCLC
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.
Study Overview
Status
Not yet recruiting
Intervention / Treatment
Study Type
Interventional
Enrollment (Estimated)
17
Phase
- Phase 2
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Yes
Description
Inclusion Criteria:
- Aged 18-75 years old, male or female;
- Patients with pathologically diagnosed non-small cell lung cancer with cerebrospinal fluid and/or MRI diagnosis of leptomeningeal metastasis;
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2;
- Expected survival time of at least 4 weeks;
- Oncologist clarification of the potential necessity of receiving systemic therapy for metastatic tumors outside the CNS;
- 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;
- 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.
Laboratory test indicators meet the following criteria:
- 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;
- 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 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);
- Coagulation function: international normalized ratio of prothrombin time ≤ ULN × 1.5, and partial thromboplastin time within the normal value;
- 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;
- Those who have not participated in another drug clinical trial within 4 weeks prior to enrollment;
- Subjects who can understand the study situation and voluntarily sign the informed consent form;
- Patients are expected to be compliant and able to follow up on efficacy and adverse events according to protocol requirements.
Exclusion Criteria:
- Diagnosis of other malignant tumors (except carcinoma in situ, basal cell carcinoma, etc.) within the previous 5 years;
- History of allergy to pemetrexed and ICIs therapy;
- Any previous intrathecal injection therapy;
- Rule out differential diagnosis of LM:a. Aseptic meningitis b. Viral meningitis c. Bacterial meningitis;
- Participation in other clinical trials or observation periods;
- 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;
- 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);
- 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.
- Either disease resulting in permanent immunosuppression or requiring permanent immunosuppressive therapy;
- Presence of active infection or serious comorbidities;
- uncontrolled epilepsy, neurologic failure, or severe neurologic impairment related to treatment;
- Presence of hereditary or acquired bleeding and thrombotic tendencies;
- History of severe injury or surgery within 1 month prior to enrollment;
- 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);
- Inability to complete an enhanced MRI;
- 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;
- Individuals considered by the investigator to be unsuitable for enrollment;
- PD-L1 expression in tumor cells <1%.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Enrolled patients were treated with an immune checkpoint inhibitor combined with pemetrexed intrathe
|
Drug 1: Tislelizumab 50 mg; Drug 2: pemetrexed 20mg.
intrathecal injection therapy
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective response rate (LM ORR) for leptomeningeal metastases.
Time Frame: 12 months.
|
Defined as the response to treatment as assessed by the investigator based on the modified Response Assessment in Neuro-Oncology Leptomeningeal Metastases (RANO-LM) criteria, containing cases of complete response, partial response, and major response.
|
12 months.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Median Progression-Free Survival (CNS-PFS) in the Central Nervous System.
Time Frame: Time from the start of intrathecal therapy to radiologic, cytologic, or LM-related clinical progression, whichever outcome occurs first, assessed up to 12 months.
|
Progression-free survival will be measured as time to radiologic, cytologic, or LM-related clinical progression.
|
Time from the start of intrathecal therapy to radiologic, cytologic, or LM-related clinical progression, whichever outcome occurs first, assessed up to 12 months.
|
Progression-Free Survival (PFS).
Time Frame: Time from the first day of administration of study drug until the first efficacy assessment of disease progression (PD) or death from any cause, assessed up to 12 months.
|
Progression-free survival will be measured as time to either progression or death.
|
Time from the first day of administration of study drug until the first efficacy assessment of disease progression (PD) or death from any cause, assessed up to 12 months.
|
Overall survival (OS).
Time Frame: Time from the date of randomisation to the date of death from any cause, assessed up to 12 months.
|
Overall survival will be measured as time to death from any cause.
|
Time from the date of randomisation to the date of death from any cause, assessed up to 12 months.
|
Disease Control Rate (DCR).
Time Frame: 12 months.
|
The DCR was defined as the proportion of patients with the best efficacy (complete response or partial response or stable disease).
|
12 months.
|
Adverse events.
Time Frame: 12 months.
|
toxicity values caused by intrathecal injection treatment.
|
12 months.
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Estimated)
November 30, 2023
Primary Completion (Estimated)
November 30, 2024
Study Completion (Estimated)
November 30, 2025
Study Registration Dates
First Submitted
November 7, 2023
First Submitted That Met QC Criteria
November 14, 2023
First Posted (Actual)
November 15, 2023
Study Record Updates
Last Update Posted (Actual)
November 15, 2023
Last Update Submitted That Met QC Criteria
November 14, 2023
Last Verified
November 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Nervous System Diseases
- Neoplasms
- Neoplasms by Site
- Neoplastic Processes
- Central Nervous System Neoplasms
- Nervous System Neoplasms
- Meningeal Neoplasms
- Neoplasm Metastasis
- Meningeal Carcinomatosis
- Molecular Mechanisms of Pharmacological Action
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Folic Acid Antagonists
- Pemetrexed
- Tislelizumab
Other Study ID Numbers
- West China Hospital of SU
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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