Phase II Study of the Combination of Cisplatin + Temozolomide in Malignant Glial Tumours in Children and Adolescents at Diagnosis or in Relapse
4 Years
20 Years
Both
Brain and Central Nervous System Tumors
Trial Information
Phase II Study of the Combination of Cisplatin + Temozolomide in Malignant Glial Tumours in Children and Adolescents at Diagnosis or in Relapse
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.
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
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Response rate after 2 courses
Safety Issue:
No
Principal Investigator
Steve Lowis, MD, PhD, BA, MRCP, MRCPCH
Investigator Affiliation:
Bristol Royal Hospital for Children
Authority:
United States: Federal Government
Study ID:
CDR0000482280
NCT ID:
NCT00360945
Start Date:
April 2004
Completion Date:
Related Keywords:
- Brain and Central Nervous System Tumors
- 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
- Nervous System Neoplasms
- Central Nervous System Neoplasms
- Glioma
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