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Background <p>Irinotecan demonstrates anti-tumor efficacy in preclinical glioma models but clinical results are modest due to drug delivery limitations. Convection enhanced delivery (CED) improves drug delivery by increasing intratumoral drug concentration. Real-time magnetic resonance imaging of infusate delivery during CED may optimize tumor coverage. This phase 1 trial examines the safety and tolerability of liposomal irinotecan and gadolinium delivered via CED using real-time MRI guidance in recurrent high-grade glioma patients.</p> Methods <p>Initially, a 3 + 3 dose-escalating, single dose trial was planned with 4 cohorts based on a fixed drug dose and volume. After 9 patients, a protocol amendment allowed for variable volume and dose of the study agent based on tumor size. The amended design specified ‘personalized’ drug volume but fixed concentration of 20&#xa0;mg/mL of liposomal irinotecan in the first cohort escalating to 40&#xa0;mg/mL in the second cohort.</p> Results <p>Eighteen patients with recurrent WHO grade 3 or 4 gliomas (diameter 1–4&#xa0;cm) were treated. Based on the tumor volume, the total dose of liposomal irinotecan was 20–680&#xa0;mg in a total volume of 2–17&#xa0;ml. Technical challenges were overcome by real-time MRI guidance and protocol amendment. The only dose-limiting toxicity (DLT) was a grade 3 stroke. Safety and survival information is presented.</p> Conclusions <p>CED of liposomal irinotecan using real-time MRI in patients with recurrent high-grade glioma is feasible. Image-guidance allowed for improved placement of CED cannulas and optimal tumor coverage. Our results warrant further study with repeat CED dosing.</p>

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A phase I study of convection-enhanced delivery (CED) of liposomal-irinotecan using real-time magnetic resonance imaging in patients with recurrent high-grade glioma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年1月6日

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  • Kazim H. Narsinh,
  • Karishma Kumar,
  • Krystof Bankiewicz,
  • Alastair J. Martin,
  • Mitchell Berger,
  • Jennifer Clarke,
  • Jennie Taylor,
  • Nancy Ann Oberheim Bush,
  • Annette M. Molinaro,
  • Manish Aghi,
  • Nicholas Butowski

摘要

Background

Irinotecan demonstrates anti-tumor efficacy in preclinical glioma models but clinical results are modest due to drug delivery limitations. Convection enhanced delivery (CED) improves drug delivery by increasing intratumoral drug concentration. Real-time magnetic resonance imaging of infusate delivery during CED may optimize tumor coverage. This phase 1 trial examines the safety and tolerability of liposomal irinotecan and gadolinium delivered via CED using real-time MRI guidance in recurrent high-grade glioma patients.

Methods

Initially, a 3 + 3 dose-escalating, single dose trial was planned with 4 cohorts based on a fixed drug dose and volume. After 9 patients, a protocol amendment allowed for variable volume and dose of the study agent based on tumor size. The amended design specified ‘personalized’ drug volume but fixed concentration of 20 mg/mL of liposomal irinotecan in the first cohort escalating to 40 mg/mL in the second cohort.

Results

Eighteen patients with recurrent WHO grade 3 or 4 gliomas (diameter 1–4 cm) were treated. Based on the tumor volume, the total dose of liposomal irinotecan was 20–680 mg in a total volume of 2–17 ml. Technical challenges were overcome by real-time MRI guidance and protocol amendment. The only dose-limiting toxicity (DLT) was a grade 3 stroke. Safety and survival information is presented.

Conclusions

CED of liposomal irinotecan using real-time MRI in patients with recurrent high-grade glioma is feasible. Image-guidance allowed for improved placement of CED cannulas and optimal tumor coverage. Our results warrant further study with repeat CED dosing.