Intrathecal Pemetrexed for SCLC Patients With Refractory Brain Metastases or Leptomeninges Metastatic

Phase 2

Not yet recruiting

• Conditions: Small-cell Lung Cancer
• Interventions: Drug: Intrathecal Pemetrexed

• Registration Number: NCT06497543
• Lead Sponsor: Hunan Province Tumor Hospital

Brief Summary

This study aimed to evaluate the efficacy and safety of intrathecal pemetrexed for SCLC patients with refractory brain metastases or leptomeningeal metastasis.

Detailed Description

This is a prospective interventional clinical study to evaluate the efficacy and safety of intrathecal pemetrexed for SCLC patients with refractory brain metastases or leptomeningeal metastasis. Approximately 80 small cell lung cancer patients with refractory brain and/or leptomeningeal metastasis were enrolled and treated with intrathecal pemetrexed, there were 40 cases in cohort 1 with refractory brain metastasis and 40 cases in cohort 2 with leptomeningeal metastasis.Cerebrospinal fluid samples will be collected before and after pemetrexed resistance to analyze molecular mechanisms. The study is expected to commence recruitment in mainland China in about September 2024. It is expected that the trial will end in April 2026.

Study Timeline

• Status Verified: 2024-07
• Study First Submitted: 2024-07-05
• Study First Submitted QC: 2024-07-05
• Study First Posted: 2024-07-11
• Last Update Submitted: 2024-07-31
• Study Start: 2024-08-01
• Last Update Posted: 2024-08-02
• Primary Completion: 2025-10-31
• Study Completion: 2026-04-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

• 1. Understand the requirements and contents of the clinical trial, and provide a signed and dated informed consent form.
• 2. Age ≥ 18 years.
• 3. Histopathology is confirmed small cell lung cancer .
• 4.Leptomeningeal metastasis (LM) is defined by the presence of typical clinical symptoms, positive cerebrospinal fluid (CSF) cytology, detection of cell-free DNA (cfDNA) in CSF by next-generation sequencing (NGS), or imaging findings consistent with typical meningeal metastases.
• 5.Patients with brain progression after whole-brain radiotherapy.
• 6. Predicted survival ≥ 12 weeks. .
• 7. ECOG 0-2.
• 8. Adequate bone marrow hematopoiesis and organ function.

Exclusion Criteria

• 1. Previously received intrathecal pemetrexed therapy for locally advanced or metastatic disease.
• 2. Subjects who have received any of the following treatments must be excluded:
• Have received radiation within 14 days prior to the first dose or have not recovered from radiation-related toxicity. Chest and extra-brain palliative radiotherapy, stereotactic radiosurgery, and stereotactic body radiotherapy may be performed 7 days prior to the first dose.
• 3. Presence of spinal cord compression or meningeal metastasis.
• 4. History of other malignant tumors within 2 years.
• 5. Adverse events (except alopecia of any degree) of CTCAE > grade 1 due to prior treatment (e.g., adjuvant chemotherapy, radiotherapy, etc.) prior to the first dose.
• 6. History of stroke or intracranial hemorrhage within 6 months prior to the first dose.
• 7. The presence of any severe or poorly controlled systemic disease, including poorly controlled hypertension and active bleeding in the judgment of the investigator.
• 8. Subjects with persistent or active infection, including but not limited to hepatitis B (HBV), hepatitis C (HCV), human immunodeficiency virus (HIV) and COVID-19 infection.
• 9. Heart-related diseases or abnormalities
• 10. Past history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis requiring steroid therapy or interstitial lung disease with active clinical symptoms, immune pneumonia caused by immunotherapy.
• 11. Refractory nausea and vomiting, chronic gastrointestinal disease, difficulty swallowing drugs, or inability to adequately absorb sunvozertinib or anlotinib due to previous bowel resection.
• 12. Live vaccine was given 2 weeks before the first medication.
• 13. Women who are breastfeeding or pregnant.
• 14. Hypersensitivity to the test drug and the ingredients.
• 15. Other conditions assessed by the investigator to be unsuitable for participation in the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cohort 2	Intrathecal Pemetrexed	Small Cell Lung Cancer patient with Leptomeningeal Metastasis
Cohort 1	Intrathecal Pemetrexed	Small Cell Lung Cancer patient with Refractory Brain Metastases

Primary Outcome Measures

Name	Time	Method
Overall Survival	Time from first subject dose to study completion, or up to last follow up	OS was defined as the duration from the start of intrathecal pemetrexed to patient death

Secondary Outcome Measures

Name	Time	Method
Adverse events (AEs)	Time from first subject dose to study completion, or up to 36 month	Number of participants with adverse events (AEs) according to CTCAE 5.0
Intracranial progression-free survival (I-PFS)	Time from first subject dose to study completion, or up to 36 month	Intracranial progression-free survival was defined as the duration from the start of intrathecal pemetrexed to the worsening of neurological symptoms, radiological confirmation of brain progression, or patient death
Intracranial Objective Response Rate (I-ORR)	Time from first subject dose to study completion, or up to 36 month	To assess Intracranial overall response rate according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by investigator, define as the proportion of subjects who have a complete response (CR) or a partial response (PR)
clinical remission rate	Time from first subject dose to study completion, or up to 36 month	Clinical Response Rate was defined as the ratio of the patient whose neurological symptoms and KPS improved according to the criteria of clinical response

Trial Locations

Locations (1)

Yongchang Zhang; 🇨🇳 Changsha, Hunan, China