Cisplatin and Temozolomide in Treating Young Patients With Malignant Glioma

NCT ID: NCT00360945

Last Updated: 2013-09-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

87 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-04-30

Brief Summary

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RATIONALE: Drugs used in chemotherapy, such as cisplatin and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving cisplatin together with temozolomide works in treating young patients with malignant glioma.

Detailed Description

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OBJECTIVES:

Primary

* Determine the objective response rate (complete and partial response) in pediatric patients with malignant gliomas treated with temozolomide and cisplatin.

Secondary

* Identify genetic, metabolic, and proteomic profiles that will provide an insight into the molecular pathways involved in the pathogenesis of these tumors.
* Link genetic changes with clinical details, histopathology, and patient outcome, thereby developing a biological basis for diagnosis, prognosis, and treatment monitoring.
* Evaluate relapse-free survival at 1 and 2 years in patients treated at diagnosis.
* Evaluate the duration of clinical response in patients treated at relapse.
* Study the health status and quality of life of these patients.
* Evaluate long-term toxicity of this therapeutic combination.
* Evaluate the ability of magnetic resonance spectroscopy vs CT scan to predict response in patients with high-grade astrocytomas.

OUTLINE: This is a multicenter, open-label, nonrandomized, parallel-group study. Patients are stratified according to disease status (newly diagnosed vs relapsed). Patients with newly diagnosed disease are further stratified according to spread of disease (localized and measurable vs diffuse unmeasurable).

* Stratum I (newly diagnosed disease): Patients receive CISTEM chemotherapy comprising cisplatin IV over 3 hours on day 1 and oral temozolomide once daily on days 2-6. Treatment repeats every 28 days for up to 7 courses. Patients who achieve responsive or stable disease after 2 courses receive 2 more courses of CISTEM chemotherapy and then undergo radiotherapy 5 days a week for 6 weeks. After completion of radiotherapy, patients may receive up to 3 more courses of CISTEM chemotherapy for a total of 7 courses.
* Stratum II (relapsed disease): Patients receive CISTEM chemotherapy for up to 7 courses as in stratum I. Patients who reach the maximum dose allowed for cisplatin may receive oral temozolomide alone indefinitely.

Tissue and blood samples are obtained at baseline and examined by immunohistochemistry, fluorescent in situ hybridization (FISH), and loss of heterozygosity. The tumor tissue is analyzed for p53, MSH2, MLH1, and MGMT.

After completion of study treatment, patients are followed periodically for 2 years.

PROJECTED ACCRUAL: A total of 87 patients will be accrued for this study.

Conditions

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Brain and Central Nervous System Tumors

Keywords

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childhood oligodendroglioma untreated childhood cerebellar astrocytoma childhood high-grade cerebral astrocytoma childhood low-grade cerebral astrocytoma recurrent childhood cerebellar astrocytoma recurrent childhood cerebral astrocytoma recurrent childhood brain tumor

Study Design

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Allocation Method

NON_RANDOMIZED

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Interventions

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cisplatin

Intervention Type DRUG

temozolomide

Intervention Type DRUG

fluorescence in situ hybridization

Intervention Type GENETIC

loss of heterozygosity analysis

Intervention Type GENETIC

immunohistochemistry staining method

Intervention Type OTHER

laboratory biomarker analysis

Intervention Type OTHER

radiation therapy

Intervention Type RADIATION

Eligibility Criteria

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Inclusion Criteria

DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed diagnosis of 1 of the following grade III or grade IV malignant glial tumors\*:

* Glioblastoma
* Anaplastic astrocytoma
* Anaplastic oligodendroglioma
* Anaplastic oligoastrocytoma
* Anaplastic ganglioglioma
* Anaplastic mixed tumor

* Glial component is essential NOTE: \*Malignant gliomas occurring as a second primary malignancy allowed
* Newly diagnosed or recurrent disease
* No malignant brain stem tumors
* Incompletely resected tumors

* No completely resected tumors
* Measurable or evaluable disease by conventional MRI

PATIENT CHARACTERISTICS:

* Lansky performance status 40-100%
* Organ toxicity ≤ grade 2
* Absolute neutrophil count ≥ 1,000/mm³
* Platelet count ≥ 100,000/mm³
* Bilirubin ≤ 1.5 times upper limit of normal (ULN)
* AST and ALT ≤ 2.5 times ULN
* Prothrombin ≥ 50%
* Fibrinogen ≥ 1.5 g/L
* Creatinine normal for age

* Creatinine ≤ 65 µmol/L (4-15 years of age)
* Creatinine ≤ 110 µmol/L (15-20 years of age)
* Audiogram with toxicity grade ≤ 2
* ECG normal
* Negative pregnancy test
* Fertile patients must use effective contraception
* No severe or life-threatening infection
* No uncontrolled developing or symptomatic intracranial hypertension

PRIOR CONCURRENT THERAPY:

* At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas) or radiotherapy for patients with relapsed disease
* No prior cisplatin or temozolomide
* No other concurrent anticancer therapy
Minimum Eligible Age

4 Years

Maximum Eligible Age

20 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Children's Cancer and Leukaemia Group

OTHER

Sponsor Role lead

Principal Investigators

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Steve Lowis, MD, PhD, BA, MRCP, MRCPCH

Role:

Bristol Royal Hospital for Children

Jacques Grill, MD, PhD

Role:

Gustave Roussy, Cancer Campus, Grand Paris

Anthony Michalski, MD

Role:

Great Ormond Street Hospital for Children NHS Foundation Trust

David A. Walker

Role:

Queen's Medical Center

Locations

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Institut Gustave Roussy

Villejuif, , France

Site Status

Our Lady's Hospital for Sick Children Crumlin

Dublin, , Ireland

Site Status

Birmingham Children's Hospital

Birmingham, England, United Kingdom

Site Status

Institute of Child Health at University of Bristol

Bristol, England, United Kingdom

Site Status

Bristol Royal Hospital for Children

Bristol, England, United Kingdom

Site Status

Addenbrooke's Hospital at Cambridge University Hospitals NHS Foundation Trust

Cambridge, England, United Kingdom

Site Status

Leeds Cancer Centre at St. James's University Hospital

Leeds, England, United Kingdom

Site Status

Leicester Royal Infirmary

Leicester, England, United Kingdom

Site Status

Royal Liverpool Children's Hospital, Alder Hey

Liverpool, England, United Kingdom

Site Status

Middlesex Hospital

London, England, United Kingdom

Site Status

Great Ormond Street Hospital for Children NHS Trust

London, England, United Kingdom

Site Status

Central Manchester and Manchester Children's University Hospitals NHS Trust

Manchester, England, United Kingdom

Site Status

Sir James Spence Institute of Child Health

Newcastle upon Tyne, England, United Kingdom

Site Status

Queen's Medical Centre

Nottingham, England, United Kingdom

Site Status

Oxford Radcliffe Hospital

Oxford, England, United Kingdom

Site Status

Children's Hospital - Sheffield

Sheffield, England, United Kingdom

Site Status

Southampton University Hospital NHS Trust

Southampton, England, United Kingdom

Site Status

Royal Marsden NHS Foundation Trust - Surrey

Sutton, England, United Kingdom

Site Status

Royal Belfast Hospital for Sick Children

Belfast, Northern Ireland, United Kingdom

Site Status

Royal Aberdeen Children's Hospital

Aberdeen, Scotland, United Kingdom

Site Status

Royal Hospital for Sick Children

Edinburgh, Scotland, United Kingdom

Site Status

Royal Hospital for Sick Children

Glasgow, Scotland, United Kingdom

Site Status

Childrens Hospital for Wales

Cardiff, Wales, United Kingdom

Site Status

Countries

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France Ireland United Kingdom

Other Identifiers

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CCLG-CNS-2004-02

Identifier Type: -

Identifier Source: secondary_id

EU-20622

Identifier Type: -

Identifier Source: secondary_id

CDR0000482280

Identifier Type: -

Identifier Source: org_study_id