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

• Status: Completed
• Trial end date: 2019-01-05
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: First Hospital of Jilin University; The First Hospital of Jilin University
• Treatments: BB 1101; Dexamethasone; Dexamethasone acetate; Folic Acid; Hydroxocobalamin; Pemetrexed; Vitamin B 12

Criteria

Inclusion Criteria:

1. Patients diagnosed as leptomeningeal metastases from non-small cell lung cancer had been received comprehensive treatment, including intrathecal methotrexate and/or cytarabine, central nervous system radiation therapy, systemic chemotherapy as well as tyrosine-kinase inhibitor drugs.

2. Patients diagnosed with recurrent leptomeningeal metastases by positive cerebrospinal fluid cytological examination and persist aggravate symptoms for more than 1 week, or increased intracranial pressure (>300 mmH2O).

3. No severe abnormal liver and kidney function; WBC≥2500/mm3, Plt≥60000/mm3;

4. No other severe chronic diseases;

5. No severe dyscrasia.

6. Signed informed consent form.

Exclusion Criteria:

1. Patients with the clinical manifestation of nervous system failure including severe encephalopathy, grade III-IV white matter lesions confirmed by imaging examination, moderate or severe coma, and glasgow coma score less than 9 points;

2. Patients with severe nervous system injury related with treatment, such as chemical meningitis;

3. Patients who had accepted systemic chemotherapy within two weeks, or new molecular targeted therapeutic drug less than one months;

4. Patients with poor compliance, or for other reasons, the researchers considered unsuitable to participate in this clinical study.