NCT05305885

An Open-label, Randomized, Multicenter Trial of Intrathecal-pemetrexed Combined With Concurrent Involved-field Radiotherapy and Intrathecal-pemetrexed Alone in Patients With Leptomeningeal Metastasis From Solid Tumors

Status unknown NA Last updated 29 September 2022

What this trial tests

NA trial testing Pemetrexed in Leptomeningeal Metastasis in 100 participants. Status unknown.

Timeline

19 August 2022

Primary endpoint
1 October 2023

1 July 2024

Quick facts

Lead sponsor	The First Hospital of Jilin University
Phase	NA
Status	Status unknown
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	100
Start date	19 August 2022
Primary completion	1 October 2023
Estimated completion	1 July 2024
Sites	1 location across China

Drugs / interventions tested

• Pemetrexed — full drug profile →
• Radiotherapy — full drug profile →

Conditions studied

• Leptomeningeal Metastasis — all drugs for Leptomeningeal Metastasis →

Sponsor

The First Hospital of Jilin University

Who can join

Adults 18 to 75, any sex, with Leptomeningeal Metastasis. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Clinical response rate
  Time frame: From date of randomization 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.
• Incidence of treatment-related adverse events
  Time frame: From date of randomization 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.

Sponsor's own description

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.

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

1. Leptomeningeal metastases from solid tumors: A Society for Neuro-Oncology and American Society of Clinical Oncology consensus review on clinical management and future directions.
   Wilcox JA, Chukwueke UN, Ahn MJ, Aizer AA, et al · · 2024 · cited 42× · PMID 38902944 · DOI 10.1093/neuonc/noae103
2. Radiation Therapy in the Management of Leptomeningeal Disease From Solid Tumors.
   Barbour AB, Kotecha R, Lazarev S, Palmer JD, et al · · 2024 · cited 14× · PMID 38405313 · DOI 10.1016/j.adro.2023.101377
3. Leptomeningeal Metastases in Melanoma Patients: An Update on and Future Perspectives for Diagnosis and Treatment.
   Steininger J, Gellrich FF, Engellandt K, Meinhardt M, et al · · 2023 · cited 11× · PMID 37511202 · DOI 10.3390/ijms241411443
4. Radiotherapy and Systemic Treatment for Leptomeningeal Disease.
   Frechette KM, Breen WG, Brown PD, Sener UT, et al · · 2024 · cited 5× · PMID 39200256 · DOI 10.3390/biomedicines12081792
5. Leptomeningeal disease in melanoma: An update on the developments in pathophysiology and clinical care.
   Smalley I, Boire A, Brastianos P, Kluger HM, et al · · 2024 · cited 5× · PMID 37622466 · DOI 10.1111/pcmr.13116
6. Radiotherapy for Leptomeningeal Carcinomatosis in Breast Cancer Patients: A Narrative Review.
   Pawłowska E, Romanowska A, Jassem J. · · 2022 · cited 5× · PMID 36010893 · DOI 10.3390/cancers14163899
7. Drug delivery in leptomeningeal disease: Navigating barriers and beyond.
   Arshad N, Biswas N, Gill J, Kesari S, et al · · 2024 · cited 4× · PMID 38995190 · DOI 10.1080/10717544.2024.2375521