Cisplatin and Temozolomide in Treating Young Patients With Malignant Glioma

The recruitment status of this study is unknown because the information has not been verified recently.
Verified November 2006 by National Cancer Institute (NCI).
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00360945
First received: August 3, 2006
Last updated: September 16, 2013
Last verified: November 2006
  Purpose

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.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Drug: cisplatin
Drug: temozolomide
Genetic: fluorescence in situ hybridization
Genetic: loss of heterozygosity analysis
Other: immunohistochemistry staining method
Other: laboratory biomarker analysis
Radiation: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of the Combination of Cisplatin + Temozolomide in Malignant Glial Tumours in Children and Adolescents at Diagnosis or in Relapse

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Response rate after 2 courses [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Relapse-free survival [ Designated as safety issue: No ]
  • Best response in patients receiving more than 2 courses [ Designated as safety issue: No ]
  • Rate of progression at 6 months and 1 and 2 years [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]

Estimated Enrollment: 87
Study Start Date: April 2004
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

Ages Eligible for Study:   4 Years to 20 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00360945

Locations
France
Institut Gustave Roussy
Villejuif, France, F-94805
Ireland
Our Lady's Hospital for Sick Children Crumlin
Dublin, Ireland, 12
United Kingdom
Birmingham Children's Hospital
Birmingham, England, United Kingdom, B4 6NH
Bristol Royal Hospital for Children
Bristol, England, United Kingdom, BS2 8BJ
Institute of Child Health at University of Bristol
Bristol, England, United Kingdom, BS2 8AE
Addenbrooke's Hospital at Cambridge University Hospitals NHS Foundation Trust
Cambridge, England, United Kingdom, CB2 2QQ
Leeds Cancer Centre at St. James's University Hospital
Leeds, England, United Kingdom, LS9 7TF
Leicester Royal Infirmary
Leicester, England, United Kingdom, LE1 5WW
Royal Liverpool Children's Hospital, Alder Hey
Liverpool, England, United Kingdom, L12 2AP
Great Ormond Street Hospital for Children NHS Trust
London, England, United Kingdom, WC1N 3JH
Middlesex Hospital
London, England, United Kingdom, W1T 3AA
Central Manchester and Manchester Children's University Hospitals NHS Trust
Manchester, England, United Kingdom, M27 4HA
Sir James Spence Institute of Child Health
Newcastle-Upon-Tyne, England, United Kingdom, NE1 4LP
Queen's Medical Centre
Nottingham, England, United Kingdom, NG7 2UH
Oxford Radcliffe Hospital
Oxford, England, United Kingdom, 0X3 9DU
Children's Hospital - Sheffield
Sheffield, England, United Kingdom, S10 2TH
Southampton University Hospital NHS Trust
Southampton, England, United Kingdom, SO16 6YD
Royal Marsden NHS Foundation Trust - Surrey
Sutton, England, United Kingdom, SM2 5PT
Royal Belfast Hospital for Sick Children
Belfast, Northern Ireland, United Kingdom, BT12 6BE
Royal Aberdeen Children's Hospital
Aberdeen, Scotland, United Kingdom, AB25 2ZG
Royal Hospital for Sick Children
Edinburgh, Scotland, United Kingdom, EH9 1LF
Royal Hospital for Sick Children
Glasgow, Scotland, United Kingdom, G3 8SJ
Childrens Hospital for Wales
Cardiff, Wales, United Kingdom, CF14 4XW
Sponsors and Collaborators
Children's Cancer and Leukaemia Group
Investigators
Investigator: Steve Lowis, MD, PhD, BA, MRCP, MRCPCH Bristol Royal Hospital for Children
Investigator: Jacques Grill, MD, PhD Gustave Roussy, Cancer Campus, Grand Paris
Investigator: Anthony Michalski, MD Great Ormond Street Hospital for Children NHS Foundation Trust
Investigator: David A. Walker Queen's Medical Centre
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00360945     History of Changes
Other Study ID Numbers: CDR0000482280, CCLG-CNS-2004-02, EU-20622
Study First Received: August 3, 2006
Last Updated: September 16, 2013
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
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

Additional relevant MeSH terms:
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Nervous System Diseases
Temozolomide
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014