Clinical trial NCT00360945: Cisplatin and Temozolomide in Treating Young Patients With Malignant Glioma
Official title: Phase II Study of the Combination of Cisplatin + Temozolomide in Malignant Glial Tumours in Children and Adolescents at Diagnosis or in Relapse
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Brain and Central Nervous System Tumors
Keywords: 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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2006-08-07
Enrollment: 87
Sex: ALL
Minimum age (years): 4
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Response rate after 2 courses
Secondary outcomes:
measure: Relapse-free survival
measure: Best response in patients receiving more than 2 courses
measure: Rate of progression at 6 months and 1 and 2 years
measure: Overall survival
Other outcomes:
Locations:
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Dublin
country: Ireland
facility: Our Lady's Hospital for Sick Children Crumlin
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
state: England
city: Bristol
country: United Kingdom
facility: Institute of Child Health at University of Bristol
state: England
city: Bristol
country: United Kingdom
facility: Bristol Royal Hospital for Children
state: England
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital at Cambridge University Hospitals NHS Foundation Trust
state: England
city: Leeds
country: United Kingdom
facility: Leeds Cancer Centre at St. James's University Hospital
state: England
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
state: England
city: Liverpool
country: United Kingdom
facility: Royal Liverpool Children's Hospital, Alder Hey
state: England
city: London
country: United Kingdom
facility: Middlesex Hospital
state: England
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children NHS Trust
state: England
city: Manchester
country: United Kingdom
facility: Central Manchester and Manchester Children's University Hospitals NHS Trust
state: England
city: Newcastle-Upon-Tyne
country: United Kingdom
facility: Sir James Spence Institute of Child Health
state: England
city: Nottingham
country: United Kingdom
facility: Queen's Medical Centre
state: England
city: Oxford
country: United Kingdom
facility: Oxford Radcliffe Hospital
state: England
city: Sheffield
country: United Kingdom
facility: Children's Hospital - Sheffield
state: England
city: Southampton
country: United Kingdom
facility: Southampton University Hospital NHS Trust
state: England
city: Sutton
country: United Kingdom
facility: Royal Marsden NHS Foundation Trust - Surrey
state: England
city: Belfast
country: United Kingdom
facility: Royal Belfast Hospital for Sick Children
state: Northern Ireland
city: Aberdeen
country: United Kingdom
facility: Royal Aberdeen Children's Hospital
state: Scotland
city: Edinburgh
country: United Kingdom
facility: Royal Hospital for Sick Children
state: Scotland
city: Glasgow
country: United Kingdom
facility: Royal Hospital for Sick Children
state: Scotland
city: Cardiff
country: United Kingdom
facility: Childrens Hospital for Wales
state: Wales
Study officials:
affiliation: Bristol Royal Hospital for Children
name: Steve Lowis, MD, PhD, BA, MRCP, MRCPCH
affiliation: Gustave Roussy, Cancer Campus, Grand Paris
name: Jacques Grill, MD, PhD
affiliation: Great Ormond Street Hospital for Children NHS Foundation Trust
name: Anthony Michalski, MD
affiliation: Queen's Medical Center
name: David A. Walker
References: