NCT05289908

Intrathecal Pemetrexed for Leptomeningeal Metastasis

Phase I/II Clinical Trial of Intrathecal Pemetrexed as First Line Intrathecal Chemotherapy in Patients With Leptomeningeal Metastasis

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 34 (actual)
• Sponsor: The First Hospital of Jilin University · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

Intrathecal chemotherapy is one of the most important treatment modalities for leptomeningeal metastasis of solid tumors. In the previous study(Intrathecal Pemetrexed for Recurrent Leptomeningeal Metastasis From Non-small Cell Lung Cancer: A Prospective Pilot Clinical Trial. ClinicalTrials.gov identification number: NCT03101579), pemetrexed presented feasibility of intrathecal administration. Pemetrexed at 10 mg dose level on the schedule of 1-2 times per week was recommended as an intrathecal administration agent for patients with refractory leptomeningeal metastases from non-small-cell lung cancer in the previous study. Moreover, the maximum-tolerated dose and recommended dose of intrathecal pemetrexed in the previous study was obtained without vitamin supplementation. Vitamin supplementation has been shown to reduce pemetrexed-induced myelosuppression. In this study, the regimen of intrathecal pemetrexed with folic acid and vitamin B12 supplementation may provide higher safety. Therefore, the purpose of this study is to investigate the maximally tolerated dose and evaluate the safety and effectiveness of intrathecal pemetrexed with vitamin supplementation as the first-line intrathecal chemotherapy in patients with leptomeningeal metastases from malignant solid tumors.

Detailed description

This is a phase I/II clinical trial. The objective of the study is patients with leptomeningeal metastases from solid tumors. Pemetrexed (Alimta, Eli Lilly and Company) is administrated by intrathecal injection, plus dexamethasone 5 mg, twice per week for 2 weeks, followed by once per week for 4 weeks. In phase I study, the initial dose of intrathecal pemetrexed is 15 mg, escalated to 20 mg, and then 25 mg.... A minimum of three patients and a maximum of six are enrolled in each cohort. A dose-limiting toxicity is defined as grade 3 neurological toxicities (e.g., chemical meningitis) or other grade 4 toxicity. If none of the three patients experiences any dose-limiting toxicity, the subsequent three patients are enrolled at the next higher dosage level. If one of three patients experiences a dose-limiting toxicity, up to three more patients are enrolled at the same level. The maximum-tolerated dose is defined as the dose where 0/3 or 1/6 patients experiences a dose-limiting toxicity with at least two patients encountering dose-limiting toxicity at the higher dose. If more than two patients experience a dose-limiting toxicity, that level is considered too toxic. The maximum-tolerated dose is exceeded and an additional three patients should be treated at the next lower dose level. Folic acid 200-400 μg is administered orally once daily, prior to the first intrathecal pemetrexed, until 21 days after the last intrathecal pemetrexed. A single dose of vitamin B12 1000 μg is administered by intramuscular injection before the first intrathecal pemetrexed, once per 3 weeks. In phase II study, the maximum-tolerated dose determined in phase I study is chosen.

Conditions

• Leptomeningeal Metastases

Interventions

Type	Name	Description
DRUG	Pemetrexed (1)	Pemetrexed (Alimta, Eli Lilly and Company) is administrated by intrathecal injection, plus dexamethasone, twice per week for 2 weeks, followed by once per week for 4 weeks. The initial dose of intrathecal pemetrexed is 15 mg, escalated to 20 mg, and then 25 mg....
DRUG	Pemetrexed (2)	The maximum-tolerated dose determined in phase I study is chosen as the treatment dose in phase II study.
DRUG	Folic Acid	Folic acid 200-400 μg is administered orally once daily, prior to the first intrathecal pemetrexed, until 21 days after the last intrathecal pemetrexed.
DRUG	Vitamin B12	A single dose of vitamin B12 1000 μg is administered by intramuscular injection before the first intrathecal pemetrexed, once per 3 weeks.
DRUG	Dexamethasone	Dexamethasone, 5 mg, intrathecal injection via lumbar puncture, simultaneously with pemetrexed, twice per week for 2 weeks, followed by once per week for 2-4 weeks.

Timeline

• Start date: 2022-02-21
• Primary completion: 2023-03-20
• Completion: 2024-03-31
• First posted: 2022-03-22
• Last updated: 2025-05-04

Locations

1 site across 1 country: China