Phase II Study of the Combination of Cisplatin + Temozolomide in Malignant Glial Tumours in Children and Adolescents at Diagnosis or in Relapse
- Determine the objective response rate (complete and partial response) in pediatric
patients with malignant gliomas treated with temozolomide and cisplatin.
- 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
- 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
- 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.
Allocation: Non-Randomized, Masking: Open Label, Primary Purpose: Treatment
Response rate after 2 courses
Steve Lowis, MD, PhD, BA, MRCP, MRCPCH
Bristol Royal Hospital for Children
United States: Federal Government