A Phase I Trial of Carboplatin Administered by Convection-Enhanced Delivery to Patients With Recurrent/Progressive Glioblastoma Multiforme
- 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
- 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
- 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
- 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
- Prior enrolment in this study.
- Concurrent anticancer drugs.
- Concurrent investigational therapies.
- Infratentorial or intraventricular tumour visible on MRI.