Merrimack Pharmaceuticals has started enrolling patients in its Phase I clinical trial of MM-398 (nanoliposomal irinotecan injection) in a highly concentrated formulation to treat recurrent high grade glioma, a type of aggressive brain tumor with poor prognosis.
University of California associate professor of Neurological Surgery and principal investigator of the study Dr Nicholas Butowski is responsible for sponsoring and conducting the Phase I trial.
Around 36 patients with recurrent high grade glioma will be enrolled in the dose-escalating, open label Phase I trial, which is being supported by research grants from the National Institutes of Health (NIH) and Merrimack.
The trial is designed to evaluate the safety of highly concentrated MM-398 when administered by convection-enhanced drug delivery in patients with recurrent high grade glioma.
Merrimack vice-president of Discovery Daryl Drummond said: "There are few options for patients with recurrent high grade gliomas, as these types of aggressive brain tumours often grow back after surgery and radiotherapy.
"We have seen encouraging results administering this highly concentrated formulation of MM-398 in a veterinary study of canines diagnosed with spontaneous brain tumors, where MM-398 was shown to extend quality of life and survival, and we are pleased to support Dr Butowski's research."
During the trial, MM-398 will be administered with gadoteridol, an MRI imaging agent to provide real time visualisation of drug distribution in the brain, through a small catheter that allows for the drug to be injected directly into the brain tumour.
This method of delivery needs small injection volume and so the company has developed a highly concentrated formulation of MM-398.
Dr Butowski said: "The blood-brain barrier is known to limit the effective delivery of anti-cancer therapies."
"By utilising an imaging-guided, direct-injection technique to deliver MM-398, we hope to increase the cytotoxic effects of the drug on the tumor with less peripheral toxicity and fewer side effects.
"MM-398 is an excellent candidate for convection-enhanced delivery due to its nanoliposomal design, which may allow the drug to be stably deposited in the tumor, thereby prolonging exposure of the tumor to the drug."
Also known as 'nal-IRI', MM-398 is being developed to treat patients with metastatic pancreatic cancer previously treated with a gemcitabine-based therapy.