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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01317212
Recruitment Status : Withdrawn (Sufficient funding could not be secured for the study)
First Posted : March 17, 2011
Last Update Posted : April 17, 2015
Information provided by (Responsible Party):
North Bristol NHS Trust

Tracking Information
First Submitted Date  ICMJE March 16, 2011
First Posted Date  ICMJE March 17, 2011
Last Update Posted Date April 17, 2015
Study Start Date  ICMJE May 2015
Estimated Primary Completion Date May 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 16, 2011)
  • Maximum tolerated infusion concentration [ Time Frame: 2 years ]
  • Complications/side-effects/tolerability/toxicity (As defined by Eastern Cooperative Oncology Group criteria) of treatment. [ Time Frame: 2 years. ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 16, 2011)
  • Serial quality of life measurements at 3-month intervals. [ Time Frame: 2 years. ]
  • Progression-free survival (PFS) based on serial MRI scans at 3-month intervals. [ Time Frame: 2 years. ]
  • Overall survival. [ Time Frame: 2 years. ]
  • Relationship between catheter location and visible carboplatin distribution based on MRI. [ Time Frame: 2 years. ]
  • Relationship between carboplatin distribution, PFS and overall survival. [ Time Frame: 2 years. ]
  • Serum carboplatin pharmacokinetics during/after intracranial infusions. [ Time Frame: 2 years. ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Dose-Escalation Study of Carboplatin Administration Into the Brain for Glioblastoma Multiforme
Official Title  ICMJE A Phase I Trial of Carboplatin Administered by Convection-Enhanced Delivery to Patients With Recurrent/Progressive Glioblastoma Multiforme
Brief Summary

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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Glioblastoma Multiforme
Intervention  ICMJE Drug: Peritumoural carboplatin administration.
Peritumoural carboplatin administration by convection-enhanced delivery (CED) through 4 implanted intracranial catheters. Infusions conducted weekly for 4 consecutive weeks.
Study Arms  ICMJE Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: April 16, 2015)
Original Estimated Enrollment  ICMJE
 (submitted: March 16, 2011)
Estimated Study Completion Date  ICMJE May 2018
Estimated Primary Completion Date May 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT01317212
Other Study ID Numbers  ICMJE 2467
2010-023454-37 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party North Bristol NHS Trust
Study Sponsor  ICMJE North Bristol NHS Trust
Collaborators  ICMJE Not Provided
Investigators  ICMJE
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
PRS Account North Bristol NHS Trust
Verification Date April 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP