Intra-pemetrexed Alone or Combined With Concurrent Radiotherapy for Leptomeningeal Metastasis

• Status: Recruiting
• Trial end date: 2024-07-01
• Target enrollment: 0
• Participant gender: All

Summary

Intrathecal chemotherapy is one of the mainstay treatment options for leptomeningeal metastases. Owing to the limited number of agents available for intrathecal chemotherapy, it is crucial to find a novel agent with efficacy and safety. In our phase 1 study, intrathecal pemetrexed showed controllable toxicities and potential promising efficacy for refractory leptomeningeal metastases from non-small-cell lung cancer patients. In our further study, intrathecal pemetrexed combined with involved-field radiation therapy was administered as the first-line intrathecal chemotherapy for leptomeningeal metastases from solid tumors. In this study, intrathecal pemetrexed combined with involved-field radiation therapy showed feasibility and controllable adverse events. It has been proved that pemetrexed as a novel intrathecal drug exhibited promising antitumor effects in cerebrospinal fluid. Moreover, the concomitant therapeutic modality is an optimal treatment option for leptomeningeal metastases from solid tumors.

Central nervous system radiotherapy is a part of the specific treatment of leptomeningeal metastases. Radiotherapy has been proved to improve neurologic function and control of parenchymal brain metastases in leptomeningeal metastases treatment. Additionally, radiotherapy is revealed to improve the efficacy and attenuate toxicity of intrathecal chemotherapy as a result of normal cerebrospinal fluid reestablishing. However, it is still controversial whether radiotherapy can improve the overall survival. We conduct this study to further demonstrate the efficacy and safety of intrathecal pemetrexed administration for patients with leptomeningeal metastases from solid tumors by multicenter study. Furthermore, the study of effective treatment modality is of great significance. The safety and antitumor activity of intrathecal pemetrexed combined with involved-field radiation therapy and intrathecal pemetrexed alone were also compared to confirm an optimized therapeutic regimen.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: The First Hospital of Jilin University
• Collaborators: Guangdong 999 Brain Hospital; Second Affiliated Hospital of Guangzhou Medical University; The Affiliated Hospital of Guangdong Medical College; The Second Hospital of Hebei Medical University
• Treatments: Pemetrexed

Criteria

Inclusion Criteria:

1. Patients with a confirmed or probable diagnosis of leptomeningeal metastasis according to European Association of Neuro-Oncology-European Society for Medical Oncology (EANO-ESMO) guidelines；Patients who have been definitely diagnosed as leptomeningeal metastasis according to cerebrospinal fluid cytology, or patients who got the clinical diagnosis by combining with neuroimaging, history of cancer, clinical manifestation, cerebrospinal fluid examination, etc.

2. Participants with histologically or cytologically confirmed disease from solid tumors;

3. Normal liver and kidney function; WBC≥4000/mm3, Plt≥100000/mm3.

Exclusion Criteria:

1. Patients with primary tumor of hematological tumors or primary central germ cell tumors;

2. Patients who had received whole brain radiotherapy in the past 3 months;

3. Patients with effective new molecular targeted therapy in 2 weeks;

4. Patients with severe encephalopathy, grade 3 leukoencephalopathy, Glasgow Coma Scale less than 8 score;

5. Patients with extensive and lethal systemic diseases with few treatment options;

6. Patients with poor compliance, or for other reasons, the researchers considered unsuitable to participate in this clinical study.