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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified February 2011 by North Bristol NHS Trust
Sponsor:
Information provided by (Responsible Party):
North Bristol NHS Trust
ClinicalTrials.gov Identifier:
NCT01317212
First received: March 16, 2011
Last updated: July 18, 2014
Last verified: February 2011
  Purpose

High-grade gliomas are the commonest primary malignant brain tumours in adults, affecting approximately 5000 people per year in the UK. Standard treatment comprises a combination of surgery, radiotherapy and chemotherapy; however this condition remains incurable and the average survival is approximately 18 months from diagnosis. There are a number of reasons for this. Firstly these tumours are highly invasive and involve important areas of brain making it impossible to remove them surgically or cure them with radiotherapy. In the majority of cases the tumour recurs within 2 to 3cm of the original site of tumour removal. Secondly, due to the presence of a barrier between the bloodstream and the brain, when drugs designed to kill tumour cells (chemotherapy) are given intravenously or orally, they frequently do not reach the tumour at a sufficient dose to have a beneficial effect. As the chemotherapy dose has to be very high for a sufficient dose to reach the tumour, drug-related side-effects are common.

Laboratory studies demonstrate that glioma tumour cells are sensitive to a number of different chemotherapies, including carboplatin. When given intravenously however, carboplatin does not reach a sufficient concentration in the tumour to have a beneficial effect. However, studies have shown that carboplatin can be infused directly into the brain at a concentration that is highly toxic to tumour cells, but not to normal brain tissue. Using very small tubes implanted around the tumour, the investigators are able to infuse carboplatin reliably and repeatedly into the area where tumours typical recur. In this study, the investigators intend to evaluate the safety of this approach and determine the optimal dose of carboplatin to administer. It is hoped that this study will also provide evidence of improved survival for patients with high-grade glioma.


Condition Intervention Phase
Glioblastoma Multiforme
Drug: Peritumoural carboplatin administration.
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Trial of Carboplatin Administered by Convection-Enhanced Delivery to Patients With Recurrent/Progressive Glioblastoma Multiforme

Resource links provided by NLM:


Further study details as provided by North Bristol NHS Trust:

Primary Outcome Measures:
  • Maximum tolerated infusion concentration [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Complications/side-effects/tolerability/toxicity (As defined by Eastern Cooperative Oncology Group criteria) of treatment. [ Time Frame: 2 years. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Serial quality of life measurements at 3-month intervals. [ Time Frame: 2 years. ] [ Designated as safety issue: No ]
  • Progression-free survival (PFS) based on serial MRI scans at 3-month intervals. [ Time Frame: 2 years. ] [ Designated as safety issue: No ]
  • Overall survival. [ Time Frame: 2 years. ] [ Designated as safety issue: No ]
  • Relationship between catheter location and visible carboplatin distribution based on MRI. [ Time Frame: 2 years. ] [ Designated as safety issue: No ]
  • Relationship between carboplatin distribution, PFS and overall survival. [ Time Frame: 2 years. ] [ Designated as safety issue: No ]
  • Serum carboplatin pharmacokinetics during/after intracranial infusions. [ Time Frame: 2 years. ] [ Designated as safety issue: No ]

Estimated Enrollment: 18
Study Start Date: May 2015
Estimated Study Completion Date: May 2018
Estimated Primary Completion Date: May 2017 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Peritumoural carboplatin administration.
    Peritumoural carboplatin administration by convection-enhanced delivery (CED) through 4 implanted intracranial catheters. Infusions conducted weekly for 4 consecutive weeks.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01317212

Contacts
Contact: Steven S Gill, MBChB MS FRCS 0117 9701212 ext 3957 steven.gill@nbt.nhs.uk
Contact: Edward A White, BM BSc(Hons) PhD MRCS 0117 9701212 ext bp1432 ew296@doctors.net.uk

Locations
United Kingdom
Department of Neurosurgery Active, not recruiting
Bristol, United Kingdom, BS16 1LE
Sponsors and Collaborators
North Bristol NHS Trust
Investigators
Principal Investigator: Steven S Gill, MBChB MS FRCS North Bristol NHS Trust
Study Director: Edward A White, BM BSc(Hons) PhD MRCS North Bristol NHS Trust
  More Information

No publications provided

Responsible Party: North Bristol NHS Trust
ClinicalTrials.gov Identifier: NCT01317212     History of Changes
Other Study ID Numbers: 2467, 2010-023454-37
Study First Received: March 16, 2011
Last Updated: July 18, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by North Bristol NHS Trust:
Glioblastoma multiforme
Carboplatin
Convection-enhanced delivery

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Carboplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 30, 2014