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

  • STATUS
    Recruiting
  • End date
    Jul 4, 2024
  • participants needed
    100
  • sponsor
    The First Hospital of Jilin University
Updated on 4 July 2022

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.

Description

In this randomized, open-label, multicenter clinical trial, we aim to compare the efficacy and safety of intrathecal pemetrexed combined with concomitant involved-field radiation therapy and intrathecal pemetrexed alone for leptomeningeal metastasis patients from solid tumor. Patients were randomly divided into two arms willing to receive involved-field radiation therapy combined with concurrent intrathecal pemetrexed and intrathecal pemetrexed alone, respectively. In concomitant therapy group, participants received induction intrathecal pemetrexed first. Then concomitant intrathecal pemetrexed and involved-field radiation therapy were given. In intrathecal pemetrexed alone group, participants received induction intrathecal pemetrexed and consolidation intrathecal pemetrexed. Pemetrexed was administrated by intrathecal injection via intraventricular administration or lumbar puncture. Induction intrathecal pemetrexed was given twice per week for 2 weeks to all participants first. Then consolidation/concomitant intrathecal pemetrexed was given once per week for 4 weeks. Involved-field radiation therapy was administrated with a total dose of 40 Gy in 20 fractions for 4 weeks to the concomitant therapy group participants. Primary endpoints were clinical response and treatment-related adverse events. Secondary endpoints were overall survival and neurological progression-free survival.

Details
Condition Leptomeningeal Metastasis
Treatment Radiotherapy, Pemetrexed
Clinical Study IdentifierNCT05305885
SponsorThe First Hospital of Jilin University
Last Modified on4 July 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

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
Participants with histologically or cytologically confirmed disease from solid tumors
Normal liver and kidney function; WBC≥4000/mm3, Plt≥100000/mm3
No history of whole brain radiotherapy

Exclusion Criteria

Patients with primary tumor of hematological tumors or primary central germ cell tumors
Patients administrated with new molecular targeted therapy which is effective for leptomeningeal metastasis in 2 weeks
Patients with severe encephalopathy, grade 3 leukoencephalopathy, Glasgow Coma Scale less than 8 score
Patients with hydrocephalus or other factors suggestive of cerebrospinal fluid circulation obstruction
Patients with extensive and lethal systemic diseases with few treatment options
Patients with poor compliance, or for other reasons, the researchers considered unsuitable to participate in this clinical study
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