Intrathecal Pemetrexed for Leptomeningeal Metastasis in EGFR-Mutant NSCLC
Launched by TAIPEI VETERANS GENERAL HOSPITAL, TAIWAN · Mar 27, 2023
Trial Information
Current as of July 01, 2025
Not yet recruiting
Keywords
ClinConnect Summary
This clinical trial is studying a new treatment option for patients with advanced non-small cell lung cancer (NSCLC) who have developed leptomeningeal metastasis (LM), a condition where cancer spreads to the membranes surrounding the brain and spinal cord. The trial will focus on using a chemotherapy drug called pemetrexed, delivered directly into the space around the spinal cord (a method known as intrathecal administration). This approach aims to improve treatment outcomes for patients who have experienced disease progression after using a common targeted therapy called osimertinib.
To be eligible for this trial, participants must be at least 20 years old and have a confirmed diagnosis of non-squamous NSCLC with specific genetic mutations. They should have shown disease progression in the brain after taking osimertinib, but their cancer outside the brain should remain stable. Participants will also need to have normal organ function and be able to understand and provide informed consent. Throughout the trial, patients can expect to receive regular monitoring to assess the treatment's safety and effectiveness. It's important to note that this study is not yet recruiting, so interested individuals should keep an eye on updates regarding participation.
Gender
ALL
Eligibility criteria
- • Inclusion criteria
- • At least 20 years of age.
- • Patients with metastatic non-squamous NSCLC harboring known EGFR activating mutation and with a diagnosis of probable or confirmed LM by the European Association of Neuro-Oncology-European Society for Medical Oncology (EANO-ESMO) guideline. \[5\] EGFR activating mutations include exon19 deletion, T790M, L858R, G719X, L861Q, or S768I.
- • Intracranial disease progression after osimertinib use, proved by contrast-enhanced MRI
- • Stable extra-cranial disease status, judged by investigators.
- • Eastern Cooperative Oncology Group (ECOG) performance status 0-3 and a minimum life expectancy of 12 weeks
- * Normal bone marrow and organ function as defined below:
- • Marrow: Hemoglobin ≥9gm/dL, ANC ≥1500/mm3 platelets ≥100,000/mm3
- • Hepatic: Serum total bilirubin ≤1.5 x upper limit of normal (ULN), ALT (SGPT) and AST (SGOT) ≤3 x ULN.
- • Renal: Creatinine clearance (Ccr) ≥45 mL/min.
- • For female patients of childbearing potential, agreement (by patient and/or partner) to use a highly effective form(s) of contraception that results in a low failure rate (\< 1% per year) when used consistently and correctly, and to continue its use for 5 months after the last dose of IP. Such methods include: combined (estrogen and progestogen containing) hormonal contraception, progestogen-only hormonal contraception associated with inhibition of ovulation together with another additional barrier method always containing a spermicide, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomized partner (on the understanding that this is the only one partner during the whole study duration), and sexual abstinence.
- • Ability to understand and willingness to sign an IRB approved written informed consent document.
- • Willing to provide CSF and plasma samples for ctDNA analysis.
- • Exclusion criteria
- • Uncontrolled extra-CNS disease which needs other systemic treatment than EGFR-TKI.
- • Uncontrolled tumor-related pain
- • Uncontrolled or symptomatic hypercalcemia (\> 1.5 mmol/L ionized calcium or Ca \> 12 mg/dL or corrected serum calcium \> ULN). Patients who are receiving denosumab prior to study enrollment must be willing and eligible to receive a bisphosphonate instead while in the study.
- • Malignancies other than NSCLC within 5 years prior to study enrollment, with the exception of those with a negligible risk of metastasis or death (e.g., expected 5-year OS \> 90%) treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous-cell skin cancer, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ treated surgically with curative intent)
- • On chronic systemic steroid therapy more than 20 mg prednisolone per day (or equivalent) or on any other form of immunosuppressive medication
- • Has received a live-virus vaccination within 30 days of planned treatment start
- • Systemic cytotoxic chemotherapy or major surgery within 2 weeks of the first dose of study medication
- • Active infection requiring therapy
- • History of Human Immunodeficiency Virus (HIV) infection.
- • Hepatitis B carrier: Patients with HBV infection were required to be receiving effective antiviral therapy and have a viral load less than 100 IU/mL at screening
- • Active Hepatitis C
- • Has received intrathecal chemotherapy within 2 weeks before the start of IP
- • Has received whole-brain radiotherapy (WBRT) within 2 weeks before the start of IP
- • Uncontrolled epilepsy
- • History of allergic reaction to intravenous pemetrexed.
- • Severe coagulation abnormality (INR \> 2).
- • Severe symptomatic hydrocephalus that requires other treatment modalities other than IP
- • Bulky intra-cranial lesion that requires other treatment modalities other than IP
About Taipei Veterans General Hospital, Taiwan
Taipei Veterans General Hospital, located in Taiwan, is a renowned medical institution dedicated to providing comprehensive healthcare and advancing medical research. As a prominent clinical trial sponsor, the hospital is committed to exploring innovative therapies and improving patient outcomes through rigorous scientific studies. With a multidisciplinary team of experienced researchers and clinicians, Taipei Veterans General Hospital prioritizes ethical standards and patient safety while contributing to the global medical community's knowledge base. Its state-of-the-art facilities and collaborative environment foster groundbreaking research that aims to address pressing healthcare challenges.
Contacts
Jennifer Cobb
Immunology at National Institute of Allergy and Infectious Diseases (NIAID)
Locations
Patients applied
Timeline
First submit
Trial launched
Trial updated
Estimated completion
Not reported
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