Cisplatin and Temozolomide in Treating Young Patients With Malignant Glioma

Brain and Central Nervous System Tumors Clinical Trial

Official title: Phase II Study of the Combination of Cisplatin + Temozolomide in Malignant Glial Tumours in Children and Adolescents at Diagnosis or in Relapse

Status Active, not recruiting

Clinical Trial Summary

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.

Clinical Trial Description

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. ;

Study Design

Allocation: Non-Randomized, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Nervous System Neoplasms

• NCT number: NCT00360945
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: April 2004