NCT03154996

Chronic Convection Enhanced Delivery of Topotecan

Chronic Convection Enhanced Delivery of Topotecan for Recurrent High Grade Gliomas

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 5 (actual)
• Sponsor: Jeffrey N. Bruce · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The primary goal of this study is to establish, for the first time, safety of prolonged intracerebral convection enhanced delivery of chemotherapy in patients with recurrent high grade glioma (HGG). Secondary objectives will include determination of topotecan (TPT) distribution and radiographic tumor response with prolonged continuous intracerebral convection-enhanced delivery (CED).

Detailed description

Malignant gliomas are among the most pernicious of human tumors - locally invasive and universally recurrent, with recurrence usually occurring within two centimeters of the original resection cavity. Although numerous chemotherapeutic drugs demonstrate significant anti-tumor activity in preclinical studies, the efficacy in clinical trials has been dismal because systemic delivery fails to achieve therapeutic drug levels in tumor cells due to various factors including limited blood-brain barrier permeability and systemic toxicity. Convection-enhanced delivery (CED) is a method of regional drug delivery that circumvents this problem. Phase 1 clinical trial has shown that a potent topoisomerase inhibitor, topotecan (TPT), can be safely and effectively delivered by CED into patients with recurrent malignant gliomas. This study will expand on these clinical results to address two current limitations to the clinical application of CED: 1) A reliable method for non-invasively monitoring drug distribution throughout the tumor and brain does not exist; and 2) Duration of CED therapy has been limited to short-term infusions secondary to the use of externalized infusion pumps. The hypothesis is that extended chronic local-regional delivery of TPT is safe, effective and feasible in patients with recurrent gliomas. TPT will be directly and chronically delivered into the tumor and surrounding brain by CED through subcutaneously implanted pumps while innovating a methodology for monitoring the drug distribution through non-invasive imaging. This strategy will overcome the limitations of chemotherapy as currently used in the treatment of gliomas, and may be applicable to other central nervous system (CNS) diseases currently limited by drug delivery barriers.

Conditions

• Gliomas

Interventions

Type	Name	Description
DRUG	Topotecan	Topotecan is a chemotherapeutic agent that is a topoisomerase inhibitor. TPT is administered through an externalized catheter and external microinfusion pump. Dose: 146 micrometers (uM)
DRUG	Gadolinium	Gadolinium is a widely available MRI contrast agent that is used routinely in clinical practice via IV administration, especially for imaging of intracranial tumors.
DEVICE	Synchromed II infusion pumps	Implanted subcutaneously to facilitate chronic infusion.

Timeline

• Start date: 2018-01-18
• Primary completion: 2021-08-20
• Completion: 2021-08-20
• First posted: 2017-05-16
• Last updated: 2022-07-05

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study