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

The Efficacy and Safety of Intrathecal Pemetrexed for SCLC Patients With Refractory Brain Metastases or Leptomeningeal Metastasis: A Phase II Study

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

Study Overview

• Status: Not yet recruiting
• Conditions: Small-cell Lung Cancer
• Intervention / Treatment: Drug: Intrathecal Pemetrexed

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 Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yongchang Zhang, MD; Phone Number: +8613873123436; Email: zhangyongchang@csu.edu.cn
• Study Contact Backup: Name: Liang Zeng, MD; Phone Number: 15974139200

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410013
      • Yongchang Zhang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 2; Small Cell Lung Cancer patient with Leptomeningeal Metastasis	Drug: Intrathecal Pemetrexed; Intrathecal pemetrexed(50mg) twice a week for 1 week (day 1 and day 5) as induction treatment, then once monthly until progressive disease.; Other Names: Pemetrexed
Experimental: Cohort 1; Small Cell Lung Cancer patient with Refractory Brain Metastases	Drug: Intrathecal Pemetrexed; Intrathecal pemetrexed(50mg) twice a week for 1 week (day 1 and day 5) as induction treatment, then once monthly until progressive disease.; Other Names: Pemetrexed

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intracranial progression-free survival (I-PFS)	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	Time from first subject dose to study completion, or up to 36 month
Intracranial Objective Response Rate (I-ORR)	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)	Time from first subject dose to study completion, or up to 36 month
clinical remission rate	Clinical Response Rate was defined as the ratio of the patient whose neurological symptoms and KPS improved according to the criteria of clinical response	Time from first subject dose to study completion, or up to 36 month
Adverse events (AEs)	Number of participants with adverse events (AEs) according to CTCAE 5.0	Time from first subject dose to study completion, or up to 36 month

Collaborators and Investigators

• Sponsor: Hunan Province Tumor Hospital
• Collaborators: Second People's Hospital of Hunan

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2024
• Primary Completion (Estimated): October 31, 2025
• Study Completion (Estimated): April 30, 2026

Study Registration Dates

• First Submitted: July 5, 2024
• First Submitted That Met QC Criteria: July 5, 2024
• First Posted (Actual): July 11, 2024

Study Record Updates

• Last Update Posted (Actual): September 19, 2024
• Last Update Submitted That Met QC Criteria: September 17, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Brain Neoplasms; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Folic Acid Antagonists; Pemetrexed
• Other Study ID Numbers: 20240705

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No