Dose-Escalation Study of Carboplatin Administration Into the Brain for Glioblastoma Multiforme

Inclusion Criteria:

• Age 18 years old or over
• Male or female
• World Health Organisation performance status 0-2
• Life expectancy greater than 3 months
• Capacity to give informed consent
• Histologically confirmed glioblastoma multiforme. Patients with a previous history of a lower grade gliomas are eligible if histology at relapse confirms glioblastoma
• Progressive and/or recurrent disease confirmed by MRI
• Progressive disease, defined as 25% or greater increase in contrast-enhanced tumour volume on T1-weighted MRI
• Supratentorial disease
• Disease confined to a single quadrant of brain
• It must be feasible to achieve sufficient carboplatin distribution in the peritumoural tissue as defined by the principal investigator and/or trial coordinator. Feasibility may be determined through the use of appropriate software that uses diffusion imaging and fluid dynamics mathematical modelling to predict infusate distribution
• Recurrent disease following conventional treatment, including surgery (biopsy or debulking), radiotherapy and chemotherapy (temozolomide)
• More than 30 days since prior chemotherapy (42 days for nitrosureas or mitomycin)
• More than 90 days since radiotherapy or radiosurgery
• More than 7 days since tumour debulking or other neurosurgery
• More than 30 days since prior investigational agents or participation in another clinical research trial
• Platelet count > or = 100,000/mm3
• Absolute neutrophil count > or = 1000mm3
• Total bilirubin no greater than 1.5 x upper limit of normal (except patients with Gilbert's syndrome)
• AST and ALT < or = to 2 times upper limit of normal
• PT and APTT no greater than control
• Creatinine clearance > 50ml/min using Cockcroft Formula
• Fertile patients must agree to use effective contraception during and for 2 months after study treatment
• Negative pregnancy test if appropriate

Exclusion Criteria:

• Clinical evidence of raised intracranial pressure.
• Concurrent medical condition that would preclude general anaesthesia.
• Severe acute infection.
• Pregnancy or breast feeding.
• Documented allergy to carboplatin or cisplatin.
• Prior participation in a trial of biological therapy (e.g. monoclonal antibodies, gene therapy, oncolytic viral therapy, immunotoxin therapy).
• Prior local chemotherapy, including administration of biodegradable polymer wafers containing carmustine.
• Prior enrolment in this study.
• Concurrent anticancer drugs.
• Concurrent investigational therapies.
• Infratentorial or intraventricular tumour visible on MRI.