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

Primary Purpose

Glioblastoma Multiforme

Status

Withdrawn

Phase

Phase 1

Locations

United Kingdom

Study Type

Interventional

Intervention

Peritumoural carboplatin administration.

About this trial

This is an interventional treatment trial for Glioblastoma Multiforme focused on measuring Glioblastoma multiforme, Carboplatin, Convection-enhanced delivery

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Department of Neurosurgery

Outcomes

Primary Outcome Measures

Maximum tolerated infusion concentration

Complications/side-effects/tolerability/toxicity (As defined by Eastern Cooperative Oncology Group criteria) of treatment.

Secondary Outcome Measures

Serial quality of life measurements at 3-month intervals.

Progression-free survival (PFS) based on serial MRI scans at 3-month intervals.

Overall survival.

Relationship between catheter location and visible carboplatin distribution based on MRI.

Relationship between carboplatin distribution, PFS and overall survival.

Serum carboplatin pharmacokinetics during/after intracranial infusions.

Full Information

NCT ID

NCT01317212

First Posted

March 16, 2011

Last Updated

April 16, 2015

Sponsor

North Bristol NHS Trust

1. Study Identification

Unique Protocol Identification Number

NCT01317212

Brief Title

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

Official Title

A Phase I Trial of Carboplatin Administered by Convection-Enhanced Delivery to Patients With Recurrent/Progressive Glioblastoma Multiforme

Study Type

Interventional

2. Study Status

Record Verification Date

April 2015

Overall Recruitment Status

Withdrawn

Why Stopped

Sufficient funding could not be secured for the study

Study Start Date

May 2015 (undefined)

Primary Completion Date

May 2017 (Anticipated)

Study Completion Date

May 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

North Bristol NHS Trust

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Glioblastoma Multiforme

Keywords

Glioblastoma multiforme, Carboplatin, Convection-enhanced delivery

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Intervention Type

Drug

Intervention Name(s)

Peritumoural carboplatin administration.

Intervention Description

Peritumoural carboplatin administration by convection-enhanced delivery (CED) through 4 implanted intracranial catheters. Infusions conducted weekly for 4 consecutive weeks.

Primary Outcome Measure Information:

Title

Maximum tolerated infusion concentration

Time Frame

2 years

Title

Complications/side-effects/tolerability/toxicity (As defined by Eastern Cooperative Oncology Group criteria) of treatment.

Time Frame

2 years.

Secondary Outcome Measure Information:

Title

Serial quality of life measurements at 3-month intervals.

Time Frame

2 years.

Title

Progression-free survival (PFS) based on serial MRI scans at 3-month intervals.

Time Frame

2 years.

Title

Overall survival.

Time Frame

2 years.

Title

Relationship between catheter location and visible carboplatin distribution based on MRI.

Time Frame

2 years.

Title

Relationship between carboplatin distribution, PFS and overall survival.

Time Frame

2 years.

Title

Serum carboplatin pharmacokinetics during/after intracranial infusions.

Time Frame

2 years.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Steven S Gill, MBChB MS FRCS

Organizational Affiliation

North Bristol NHS Trust

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Edward A White, BM BSc(Hons) PhD MRCS

Organizational Affiliation

North Bristol NHS Trust

Official's Role

Study Director

Facility Information:

Facility Name

Department of Neurosurgery

City

Bristol

ZIP/Postal Code

BS16 1LE

Country

United Kingdom

12. IPD Sharing Statement

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

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