Intrathecal Pemetrexed for Leptomeningeal Metastasis From Lung Adenocarcinoma That Progressed After Osimertinib.

Phase 2

Not yet recruiting

• Conditions: Leptomeningeal Metastasis
• Interventions: Drug: Pemetrexed

• Registration Number: NCT06296745
• Lead Sponsor: Guangzhou Medical University

Brief Summary

Pemetrexed is one of the first-line chemotherapeutic agents for non-squamous non-small cell lung cancer (NSCLC). Since 2017, intrathecal pemetrexed has shown good efficacy for patients with leptomeningeal metastases from NSCLC. It has been recommended as the preferred drug for intrathecal chemotherapy by the Chinese Society of Clinical Oncology (CSCO) guidelines. Tyrosine kinase inhibitors (TKIs) play a promising role in treating non-small cell lung cancer patients with epidermal growth factor receptor (EGFR) mutations. An international multi-center clinical study published in 2019 confirmed that double dose of osimertinib showed significant improvement in leptomeningeal metastases from NSCLC with EGFR exon 19 deletion or exon 21 L858R/T790M mutation. It makes TKIs the mainstay of treatment for patients with EGFR-mutant NSCLC with leptomeningeal metastases. However, the choice of treatment after resistance to targeted therapy is a hot topic in clinical practice, with 78% of patients in the study above who responded to double-dose osimertinib still showing progression at the time of follow-up. The purpose of this study was to observe the safety and efficacy of intrathecal pemetrexed for leptomeningeal metastasis from lung adenocarcinoma that progressed after a double dose of a third-generation TKI such as osimertinib.

Detailed Description

This study is a single arm, open and phase II clinical trial. Consecutive patients with leptomeningeal metastases from lung adenocarcinoma that progressed after a double dose of a third-generation TKI such as osimertinib are enrolled in this study. Concomitant regimen consisted of intrathecal chemotherapy (via lumbar puncture, pemetrexed 15 mg, plus dexamethasone 5 mg, twice a week for 2 weeks as an induction phase, followed by once a week for 4 weeks as a consolidation phase. Thereafter, the maintenance phase is once a month). The RANO proposal for response criteria of leptomeningeal metastasis was used to assess the clinical response in this study.

Study Timeline

• Status Verified: 2024-02
• Study First Submitted: 2024-02-29
• Study First Submitted QC: 2024-03-05
• Last Update Submitted: 2024-03-05
• Study First Posted: 2024-03-06
• Last Update Posted: 2024-03-06
• Study Start: 2024-03-20
• Primary Completion: 2026-01-20
• Study Completion: 2026-03-20

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

1. Male or female aged between 18 and 75 years.
2. Histologically or cytologically confirmed diagnosis of NSCLC with single activating EGFR mutations (L858R or Exon19Del).
3. Confirmed diagnosis of leptomeningeal metastasis according to ESMO/ EANO guidelines.
4. Progression after previous double doses of third-generation TKIs such as Osimertinib.
5. Normal liver and kidney function; WBC≥4000/mm3, Plt≥100000/mm3.
6. No history of severe nervous system disease.
7. No severe dyscrasia.

Exclusion Criteria

1. Any evidence of nervous system failure, including severe encephalopathy, grade 3 or 4 leukoencephalopathy on imaging, and Glasgow Coma Score less than 11.
2. Any evidence of extensive and lethal progressive systemic diseases without effective treatment.
3. Patients with poor compliance or other reasons that were unsuitable for this study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Group	Pemetrexed	Intra-pemetrexed

Primary Outcome Measures

Name	Time	Method
Clinical response rate	From date of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months.	The response assessment in neuro-oncology criteria (RANO) proposal for response criteria of leptomeningeal metastasis was used to assess the clinical response in this study.
Neurological progression-free survival (NPFS)	From date of treatment until the date of first documented neurological progression or date of death from any cause, whichever came first, assessed up to 6 months.	NPFS was defined as time from the start of treatment until neurological progression or death. The neurological progression was determined based on the RANO proposal evaluation criteria which have been established and published on Neuro Oncol.

Secondary Outcome Measures

Name	Time	Method
Overall survival	From the enrollment of this study until date of death from any cause, whichever came first, or the last follow-up (at least 7 months).	Survival time was recorded since the date of patient enrollment. All patients were followed up until death or the end of the study.
Incidence of treatment-related adverse events	From date of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months.	The incidence of treatment-related adverse events were measured for determining tolerability and safety. Adverse events (AEs) are evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE, version 4.03). Events of grade 3-5 are defined as moderate and severe adverse events.