Intrathecal Pemetrexed for Recurrent Leptomeningeal Metastases From Non-small Cell Lung Cancer
Condition: Leptomeningeal Metastases
MeSH terms: Neoplasm Metastasis; Meningeal Carcinomatosis
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): Pemetrexed; Dexamethasone; Folic Acid; Vitamin B12
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Pemetrexed,10-15 mg, intrathecal injection via lumbar puncture, twice per week for 2 weeks, followed by once per week for 2-4 weeks.; 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.; Folic acid, 400 μg, oral, once per day, prior to the first intrathecal pemetrexed, until 21 days after the last intrathecal pemetrexed.; A single dose of vitamin B12 1000 μg, intramuscular injection, before the first intrathecal pemetrexed.
Intervention MeSH terms: Folic Acid; Vitamin B 12; Dexamethasone; Pemetrexed
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Leptomeningeal metastasis; Recurrence; Intrathecal chemotherapy; Pemetrexed