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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00360945
• Other study ID #: CDR0000482280
• Secondary ID: CCLG-CNS-2004-02
• Status: Active, not recruiting
• Phase: Phase 2
• First received: August 3, 2006
• Last updated: September 16, 2013
• Start date: April 2004

Study information

• Verified date: November 2006
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 87
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 4 Years to 20 Years

Eligibility

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

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

Intervention

Drug:
• cisplatin

• temozolomide

Genetic:
• fluorescence in situ hybridization

• loss of heterozygosity analysis

Other:
• immunohistochemistry staining method

• laboratory biomarker analysis

Radiation:
• radiation therapy

Locations

Country	Name	City	State
France	Institut Gustave Roussy	Villejuif
Ireland	Our Lady's Hospital for Sick Children Crumlin	Dublin
United Kingdom	Royal Aberdeen Children's Hospital	Aberdeen	Scotland
United Kingdom	Royal Belfast Hospital for Sick Children	Belfast	Northern Ireland
United Kingdom	Birmingham Children's Hospital	Birmingham	England
United Kingdom	Bristol Royal Hospital for Children	Bristol	England
United Kingdom	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	Childrens Hospital for Wales	Cardiff	Wales
United Kingdom	Royal Hospital for Sick Children	Edinburgh	Scotland
United Kingdom	Royal Hospital for Sick Children	Glasgow	Scotland
United Kingdom	Leeds Cancer Centre at St. James's University Hospital	Leeds	England
United Kingdom	Leicester Royal Infirmary	Leicester	England
United Kingdom	Royal Liverpool Children's Hospital, Alder Hey	Liverpool	England
United Kingdom	Great Ormond Street Hospital for Children NHS Trust	London	England
United Kingdom	Middlesex Hospital	London	England
United Kingdom	Central Manchester and Manchester Children's University Hospitals NHS Trust	Manchester	England
United Kingdom	Sir James Spence Institute of Child Health	Newcastle-Upon-Tyne	England
United Kingdom	Queen's Medical Centre	Nottingham	England
United Kingdom	Oxford Radcliffe Hospital	Oxford	England
United Kingdom	Children's Hospital - Sheffield	Sheffield	England
United Kingdom	Southampton University Hospital NHS Trust	Southampton	England
United Kingdom	Royal Marsden NHS Foundation Trust - Surrey	Sutton	England

Sponsors (1)

Lead Sponsor	Collaborator
Children's Cancer and Leukaemia Group

Countries where clinical trial is conducted

France,  Ireland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response rate after 2 courses			No
Secondary	Relapse-free survival			No
Secondary	Best response in patients receiving more than 2 courses			No
Secondary	Rate of progression at 6 months and 1 and 2 years			No
Secondary	Overall survival			No