Clinical Trial of Convection Enhanced Delivery of Nanoliposomal CPT11 for Brain Tumors

At UCSF we have spent several years studying ways to deliver therapeutic agents into the brain in sufficient concentrations to kill tumor cells, but minimize toxicity to normal tissues. Today, a new clinical trial combines several cutting-edge strategies for brain tumor treatment – many of which were developed at UCSF – with the goal of increasing survival and reducing side effects.

The drug CPT-11 (also called irinotecan) has been encapsulated in a liposome to alter its pharmacokinetic properties, making it more stable and able to stay in tissue longer. Investigators at the Brain Tumor Research Center worked with the NCI Drug Development Group and industry partners for GMP manufacturing, toxicology and clinical development of this new nanoparticle drug.

But a key component for success is to ensure that the initial infusion of the agent is spreading throughout the target region, which has been a problem for other trials of infusates. In our phase 1 trial, neurosurgeons use ClearPoint to visualize the infusion of chemotherapeutic agent CPT-11 into the brain in real time, allowing them to adjust the infusion parameters if necessary.

Clearpoint was developed at UCSF by Philip Starr MD, PhD, Paul Larson MD, and Alistair Martin PhD, and uses an MR-compatible, skull-mounted device for performing implantation of deep brain stimulator electrodes or drug infusion cannulae in the MR scanner. ClearPoint has successfully been used to monitor infusions patients with brain tumors and Parkinson’s disease at UCSF.

This trial also employs a strategy to bypass the blood-brain barrier to allow higher concentrations of drug to reach the tumor than could be achieved through systemic administration. Using convection enhanced delivery – developed and refined in the laboratory of Krystof Bankiewicz MD, PhD – a pressure gradient at the tip of the cannula pushes interstitial fluid out of the way, enabling coverage of larger brain volumes than could be achieved by diffusion alone. This strategy shows superior localization and retention of the drug when compared with systemic delivery, and the slow and sustained release of drug from the liposome provides an additional safety margin.

To find out more about this trial, contact the principal investigators Nicholas Butowski MD (nicholas.butowski@ucsf.edu) and Manish Aghi MD, PhD (manish.aghi@ucsf.edu).

To inquire about patients’ participation, contact our Neuro-Oncology New-Patient Coordinator at NeuroOncNewPtCoord@ucsf.edu.