NCT03101579

Intrathecal Pemetrexed for Recurrent Leptomeningeal Metastases From Non-small Cell Lung Cancer

Intrathecal Pemetrexed for Recurrent Leptomeningeal Metastasis From Non-small Cell Lung Cancer: A Prospective Pilot Clinical Trial

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 13 (actual)
• Sponsor: The First Hospital of Jilin University · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

It has been proved that intrathecal chemotherapy is the main treatment strategy for leptomeningeal metastases. At present, the commonly used drugs for intrathecal chemotherapy include methotrexate, cytarabine, and liposomal cytarabine. In recent decades, no new effective drugs have been discovered for intrathecal chemotherapy. The recurrence of leptomeningeal metastases is inevitable even after aggressive treatment. There is no effective treatment for recurrent leptomeningeal metastases after comprehensive treatment which includes intrathecal methotrexate and/or cytarabine, central nervous system radiation therapy, systemic chemotherapy as well as tyrosine-kinase inhibitor drugs. The quality of life is extremely poor, and the patients always die in short time. Pemetrexed is a newer multitargeted antifolate which has shown activity in various tumors. It has higher effectiveness and safety, which has been used as the first-line treatment of non-small cell lung cancer. In animal studies, pemetrexed was demonstrated to suppress tumor growth completely in mice with two types of transplanted human colon xenografts resistant to methotrexate. Therefore, the purpose of the study is to evaluate the safety and feasibility of intrathecal pemetrexed in patients with recurrent leptomeningeal metastases from non-small cell lung cancer.

Detailed description

This is a single arm clinical trial. The objective of the study is patients with recurrent or progressive leptomeningeal metastases from non-small cell lung cancer after leptomeningeal metastases-related treatment. The regimen of pemetrexed (Alimta, Eli Lilly and Company) is 10/15/20 mg, plus dexamethasone 5 mg, twice per week for 2 weeks, followed by once per week for 2-4 weeks. Pemetrexed and dexamethasone are administrated by intrathecal injection via lumbar puncture. Folic acid and vitamin B12 are administered to reduce the frequency of myelosuppression. 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. To detect the pharmacokinetics of intrathecal pemetrexed, the serum and cerebrospinal fluid samples are collected. These samples would be analyzed by spectrometer for drug concentration.

Conditions

• Leptomeningeal Metastases

Interventions

Type	Name	Description
DRUG	Pemetrexed	Pemetrexed,10-15 mg, intrathecal injection via lumbar puncture, twice per week for 2 weeks, followed by once per week for 2-4 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.
DRUG	Folic Acid	Folic acid, 400 μg, oral, once per day, 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, intramuscular injection, before the first intrathecal pemetrexed.

Timeline

• Start date: 2017-03-01
• Primary completion: 2018-09-15
• Completion: 2019-01-05
• First posted: 2017-04-05
• Last updated: 2019-03-19

Locations

1 site across 1 country: China