Intrathecal Pemetrexed Combined With High-dose Furmonertinib and Beva for EGFR-m NSCLC With Leptomeningeal Metastases

NCT06537297 | Not Yet Recruiting Phase 2

• 1 other identifier: 20240801
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This study aimed to evaluate the efficacy and safety of intrathecal pemetrexed with high-dose Furmonertinib plus bevacizumab for EGFR-mutant non-small cell lung cancer patients with leptomeningeal metastases after resistance to third-generation EGFR-TKIs.

Conditions

Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• LM-overall survival

  LM-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 Outcomes (3)

• Extracranial progression-free survival

  Time from first dose to the progression of extracranial disease or patient death or last follow up

• Clinical response rate

  Time from first dose to the improvement of neurological symptoms and KPS score

• Adverse events (AEs)

  From first dose until 28 days after the last dose, up to 24 month

Study Arms (1)

Intrathecal Pemetrexed with double Furmonertinib plus bevacizumab

EXPERIMENTAL

Drug: Intrathecal Pemetrexed and high-dose Furmonertinib plus bevacizumab

Interventions

Intrathecal Pemetrexed and high-dose Furmonertinib plus bevacizumab DRUG

* Intrathecal pemetrexed(50mg) twice a week for 1 week (day 1 and day 5) as induction treatment, then once monthly; * Furmonertinib(160mg QD); * bevacizumab(5mg/kg，once monthly) until progressive disease.

Also known as: intrathecal pemetrexed, high-dose furmonertinib, bevacizumab

Intrathecal Pemetrexed with double Furmonertinib plus bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Understand the requirements and contents of the clinical trial, and provide a signed and dated informed consent form.
• \. Age ≥ 18 years.
• \. Histopathology confirmed Non-small cell lung cancer.
• \. confirmed or probable leptomeningeal metastases according to EANO-ESMO guidelines or known leptomeningeal metastases progression after third generation of EGFR-TKIs failure.
• 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.
• ECOG 0 - 2.
• \. Predicted survival ≥ 12 weeks.
• \. Adequate bone marrow hematopoiesis and organ function.

You may not qualify if:

• \. Previously received intrathecal pemetrexed therapy for locally advanced or metastatic disease.
• \. 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.
• \. Presence of spinal cord compression.
• \. History of other malignant tumors within 2 years.
• \. Adverse events (except alopecia of any degree) of CTCAE \> grade 4 due to prior treatment (e.g., adjuvant chemotherapy, radiotherapy, etc.) prior to the first dose.
• \. History of stroke or intracranial hemorrhage within 6 months prior to the first dose.
• \. The presence of any severe or poorly controlled systemic disease, including poorly controlled hypertension and active bleeding in the judgment of the investigator.
• \. 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.
• \. Heart-related diseases or abnormalities
• \. 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.
• \. Refractory nausea and vomiting, chronic gastrointestinal disease, difficulty swallowing drugs, or inability to adequately absorb Furmonertinib due to previous bowel resection.
• \. Live vaccine was given 2 weeks before the first medication.
• \. Women who are breastfeeding or pregnant.
• \. Hypersensitivity to the test drug and the ingredients.
• \. Other conditions assessed by the investigator to be unsuitable for participation in the study.

Sponsors & Collaborators

• Hunan Province Tumor Hospital: lead

Study Sites (1)

Hunan Cancer Hospital

Changsha, Hunan, 410013, China

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

aflutinib; Bevacizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Yongchang Zhang, MD

CONTACT

+8613873123436; zhangyongchang@csu.edu.cn

Liang zeng, MD

CONTACT

15974139200

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Medical Oncology, Director of Early Clinical Trial Center

Study Record Dates

• First Submitted: July 31, 2024
• First Posted: August 5, 2024
• Study Start: September 30, 2024
• Primary Completion: August 31, 2025
• Study Completion: April 30, 2026
• Last Updated: September 20, 2024

Record last verified: 2024-09

Locations

CN (1)