Cisplatin and Temozolomide in Treating Young Patients With Malignant Glioma
- Conditions
- Brain and Central Nervous System Tumors
- Registration Number
- NCT00360945
- Lead Sponsor
- Children's Cancer and Leukaemia Group
- Brief 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.
- Detailed 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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 87
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Response rate after 2 courses
- Secondary Outcome Measures
Name Time Method Overall survival Relapse-free survival Rate of progression at 6 months and 1 and 2 years Best response in patients receiving more than 2 courses
Trial Locations
- Locations (22)
Birmingham Children's Hospital
🇬🇧Birmingham, England, United Kingdom
Royal Aberdeen Children's Hospital
🇬🇧Aberdeen, Scotland, United Kingdom
Institut Gustave Roussy
🇫🇷Villejuif, France
Bristol Royal Hospital for Children
🇬🇧Bristol, England, United Kingdom
Great Ormond Street Hospital for Children NHS Trust
🇬🇧London, England, United Kingdom
Central Manchester and Manchester Children's University Hospitals NHS Trust
🇬🇧Manchester, England, United Kingdom
Queen's Medical Centre
🇬🇧Nottingham, England, United Kingdom
Children's Hospital - Sheffield
🇬🇧Sheffield, England, United Kingdom
Oxford Radcliffe Hospital
🇬🇧Oxford, England, United Kingdom
Southampton University Hospital NHS Trust
🇬🇧Southampton, England, United Kingdom
Royal Belfast Hospital for Sick Children
🇬🇧Belfast, Northern Ireland, United Kingdom
Leicester Royal Infirmary
🇬🇧Leicester, England, United Kingdom
Our Lady's Hospital for Sick Children Crumlin
🇮🇪Dublin, Ireland
Institute of Child Health at University of Bristol
🇬🇧Bristol, England, United Kingdom
Addenbrooke's Hospital at Cambridge University Hospitals NHS Foundation Trust
🇬🇧Cambridge, England, United Kingdom
Royal Liverpool Children's Hospital, Alder Hey
🇬🇧Liverpool, England, United Kingdom
Middlesex Hospital
🇬🇧London, England, United Kingdom
Sir James Spence Institute of Child Health
🇬🇧Newcastle-Upon-Tyne, England, United Kingdom
Royal Marsden NHS Foundation Trust - Surrey
🇬🇧Sutton, England, United Kingdom
Royal Hospital for Sick Children
🇬🇧Glasgow, Scotland, United Kingdom
Childrens Hospital for Wales
🇬🇧Cardiff, Wales, United Kingdom
Leeds Cancer Centre at St. James's University Hospital
🇬🇧Leeds, England, United Kingdom