Intrathecal Pemetrexed for Leptomeningeal Metastasis

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.

Conditions

• Leptomeningeal Metastases

Interventions

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.

Sponsors & Collaborators

• Affiliated Hospital of Guangdong Medical University

  collaborator OTHER

• Second Affiliated Hospital of Guangzhou Medical University

  collaborator OTHER

• Guangdong 999 Brain Hospital

  collaborator OTHER

• The Second Hospital of Hebei Medical University

  collaborator OTHER

• Panjin Liaoyou Gem Flower Hospital

  collaborator UNKNOWN

• Wuxi People's Hospital

  collaborator OTHER

• Huizhou Third People's Hospital, Guangzhou Medical University

  collaborator OTHER

• The First Hospital of Jilin University

  lead OTHER

Principal Investigators

• Zhenyu Pan · The First Hospital of Jilin University

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-02-21

Primary Completion

2023-03-20

Completion

2024-03-31

Countries

• China

Study Locations