Efficacy and Resistance Mechanisms of IP in NSCLC With Leptomeningeal Metastases (EPIC)

To Investigate the Efficacy and Resistance Mechanisms of Intrathecal Pemetrexed in Advanced Non-small Cell Lung Cancer (NSCLC) Patients Harboring Oncogenic Mutations With Leptomeningeal Metastases

This is a prospective interventional study clinical study to investigate the efficacy and resistance mechanisms of intrathecal pemetrexed in patients with driver gene mutations advanced NSCLC with leptomeningeal metastases.

Study Overview

• Status: Recruiting
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Intrathecal pemetrexed

Detailed Description

This is a prospective interventional clinical study aimed at investigating the efficacy and resistance mechanisms of intrathecal pemetrexed in advanced NSCLC patients with EGFR, ALK, and ROS1 mutations presenting leptomeningeal metastases. Approximately 30 advanced NSCLC patients with EGFR, ALK, and ROS1 mutations, who have developed leptomeningeal metastases following TKI resistance, will receive intrathecal pemetrexed. Cerebrospinal fluid samples will be collected before and after pemetrexed resistance to analyze molecular mechanisms and differences. Second-generation gene detection will be performed to identify potential resistance mechanisms to pemetrexed. The study is expected to commence recruitment in mainland China around April 2024, with an anticipated completion date in April 2025.

• Study Type: Interventional
• Enrollment (Estimated): 220
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Liang Zeng; Phone Number: 15974139200; Email: 530490930@qq.com
• Study Contact Backup: Name: Zhang Yongchang, professor; Phone Number: 13873123436; Email: zhanglei1152@126.com

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410013
      • Recruiting
      • Hunan Cancer Hospital
      • Contact: Yongchang Zhang, MD; Phone Number: +86 731 89762323; Email: zhangyongchang@csu.edu.cn
      • Principal Investigator: Yongchang Zhang, MD
      • Contact: Email: zhangyongchang@csu.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age ≥ 18 years.
2. Histopathology or cytology confirmed metastatic non-small cell lung cancer with leptomeningeal metastasis after TKI resistant.
3. EGFR mutant, ALK fusion, ROS1 fusion, and other oncogenic alterations including RET fusion, BRAF mutation, NTRK fusion, KRAS mutation was confirmed by an accredited local laboratory.
4. Adequate bone marrow hematopoiesis and organ function
5. Agree to receive intrathecal pemetrexed
6. ECOG 0 - 2.
7. Predicted survival ≥ 12 weeks.

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: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intrathecal pemetrexed	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
Intracranial progression-free survival (I-PFS)	Intracranial progression-free survival was defined as the duration from the start of IP 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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
System progression-free survival (s-PFS)	System progression-free survival was defined as the duration from the start of IP 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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival Time	Overall Survival Time was defined as the duration from the start of IP to patient death	Time from first subject dose to study completion, or up to 36 month

Collaborators and Investigators

• Sponsor: Hunan Province Tumor Hospital
• Collaborators: Hunan Cancer Hospital
• Investigators: Principal Investigator: YONGCHANG ZHANG, Hunan Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): April 30, 2027

Study Registration Dates

• First Submitted: April 23, 2024
• First Submitted That Met QC Criteria: May 28, 2024
• First Posted (Actual): June 4, 2024

Study Record Updates

• Last Update Posted (Actual): June 4, 2024
• Last Update Submitted That Met QC Criteria: May 28, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Folic Acid Antagonists; Pemetrexed
• Other Study ID Numbers: 20240442

Drug and device information, study documents

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