Combination Chemotherapy With or Without Radiation Therapy in Treating Children With Brain Tumors

Management of Children Aged Less Than 3 Years With Brain Tumors

RATIONALE: Drugs used in chemotherapy 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. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving radiation therapy after chemotherapy may kill any remaining tumor cells.

PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with or without radiation therapy works in treating children with brain tumors.

Study Overview

• Status: Unknown
• Conditions: Brain and Central Nervous System Tumors; Neuroblastoma
• Intervention / Treatment: Drug: carboplatin; Drug: cyclophosphamide; Radiation: radiation therapy; Drug: methotrexate; Drug: vincristine sulfate; Drug: cisplatin

Detailed Description

OBJECTIVES:

• Determine the response rate in children under 36 months of age with primary brain or brain stem tumors treated with vincristine, methotrexate, carboplatin, cyclophosphamide, and cisplatin with or without radiotherapy.
• Determine the event-free survival and overall survival in children treated with this regimen.
• Determine the pattern of local recurrence or occurrence of CNS metastases in children treated with this regimen.
• Determine the quality of life in children treated with this regimen.
• Determine the tolerability and long-term toxicity of this regimen in these children.
• Determine the proportion of children who require radiotherapy after treatment with this regimen.
• Determine the prognosis of children who receive both chemotherapy and radiotherapy.
• Determine the nature and behavior of brain tumors in very young children.

OUTLINE: This is a multicenter study.

• Chemotherapy: Patients receive vincristine IV on days 0, 14, and 28; carboplatin IV over 4 hours on day 0; methotrexate IV continuously over 24 hours on day 14; cyclophosphamide IV over 4 hours on day 28; and cisplatin IV continuously over 48 hours on days 42 and 43. Courses repeat every 56 days (8 weeks) for up to 12 months. Patients who achieve a complete response proceed to observation, as do those achieving a partial response with no tumor present on biopsy. Patients with biopsy proven residual tumors after 12 months of chemotherapy or recurrent tumors that don't have the potential to spread through the cerebrospinal fluid (CSF) proceed to local radiotherapy. Patients with unresponsive disease or progressive disease that has the potential to spread through the CSF proceed to craniospinal radiotherapy.
• Local radiotherapy: Patients undergo local radiotherapy 5 days a week for 5-5½ weeks.
• Craniospinal radiotherapy: Patients undergo craniospinal radiotherapy 5 days a week for 4 weeks.

Quality of life is assessed periodically.

After completion of study treatment, patients are followed periodically for at least 2 years.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• Ireland
  • Dublin, Ireland, 12
    • Our Lady's Hospital For Sick Children
• United Kingdom
  • England
    • Birmingham, England, United Kingdom, B4 6NH
      • Birmingham Children's Hospital
    • Bristol, England, United Kingdom, BS2 8AE
      • Institute of Child Health at University of Bristol
    • Cambridge, England, United Kingdom, CB2 2QQ
      • Addenbrooke's Hospital at Cambridge University Hospitals NHS Foundation Trust
    • Leeds, England, United Kingdom, LS9 7TF
      • Leeds Cancer Centre at St. James's University Hospital
    • Leicester, England, United Kingdom, LE1 5WW
      • Leicester Royal Infirmary
    • Liverpool, England, United Kingdom, L12 2AP
      • Royal Liverpool Children's Hospital, Alder Hey
    • London, England, United Kingdom, E1 1BB
      • Royal London Hospital
    • London, England, United Kingdom, WC1N 3JH
      • Great Ormond Street Hospital for Children NHS Trust
    • Manchester, England, United Kingdom, M27 4HA
      • Central Manchester and Manchester Children's University Hospitals NHS Trust
    • Newcastle-Upon-Tyne, England, United Kingdom, NE1 4LP
      • Sir James Spence Institute of Child Health
    • Nottingham, England, United Kingdom, NG7 2UH
      • Queen's Medical Centre
    • Oxford, England, United Kingdom, 0X3 9DU
      • Oxford Radcliffe Hospital
    • Sheffield, England, United Kingdom, S10 2TH
      • Children's Hospital - Sheffield
    • Southampton, England, United Kingdom, SO16 6YD
      • Southampton General Hospital
    • Sutton, England, United Kingdom, SM2 5PT
      • Royal Marsden NHS Foundation Trust - Surrey
  • Northern Ireland
    • Belfast, Northern Ireland, United Kingdom, BT12 6BE
      • Royal Belfast Hospital for Sick Children
  • Scotland
    • Aberdeen, Scotland, United Kingdom, AB25 2ZG
      • Royal Aberdeen Children's Hospital
    • Edinburgh, Scotland, United Kingdom, EH9 1LF
      • Royal Hospital for Sick Children
    • Glasgow, Scotland, United Kingdom, G3 8SJ
      • Royal Hospital for Sick Children
  • Wales
    • Cardiff, Wales, United Kingdom, CF14 4XW
      • Childrens Hospital for Wales

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 3 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Diagnosis of 1 of the following:

  • Brain stem tumor (histological confirmation not required)

  • Histologically confirmed primary intracranial brain tumor of 1 of the following histologies:

    • Anaplastic (malignant) astrocytoma
    • Glioblastoma
    • Anaplastic (malignant) oligodendroglioma
    • Ependymoma
    • Anaplastic (malignant) ependymoma
    • Anaplastic (malignant) oligoastrocytoma
    • Choroid plexus carcinoma
    • Astroblastoma
    • Polar spongioblastoma
    • Gliomatosis cerebri
    • Anaplastic (malignant) ganglioglioma
    • Pineoblastoma
    • Mixed pineocytoma or pineoblastoma
    • Medulloepithelioma
    • Neuroblastoma
    • Ependymoblastoma
    • Primitive neuroectodermal tumors (PNETs), including medulloblastoma or cerebral or spinal PNETs
• Has undergone surgery or biopsy of the tumor within the past 2-4 weeks

PATIENT CHARACTERISTICS:

• No concurrent unrelated disease, including hematological or renal disease, that would preclude study treatment

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy or radiotherapy
• Prior steroids allowed

• No concurrent steroids as anti-emetics

  • Concurrent steroids allowed for control of tumor-related symptoms

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Response rate
Event-free survival
Tolerance
Local recurrence or occurrence of CNS metastases
Quality of survival
Long-term toxicity
Proportion of patients requiring radiotherapy
Prognosis of children who receive both chemotherapy and radiotherapy
Nature and behavior of brain tumors

Collaborators and Investigators

• Sponsor: Children's Cancer and Leukaemia Group
• Investigators: Study Chair: Richard Grundy, MD, PhD, Queen's Medical Center

Study record dates

Study Major Dates

• Study Start: June 1, 1992

Study Registration Dates

• First Submitted: January 24, 2006
• First Submitted That Met QC Criteria: January 24, 2006
• First Posted (Estimate): January 25, 2006

Study Record Updates

• Last Update Posted (Estimate): September 20, 2013
• Last Update Submitted That Met QC Criteria: September 19, 2013
• Last Verified: June 1, 2007

More Information

Terms related to this study

• Keywords: untreated childhood brain stem glioma; childhood high-grade cerebral astrocytoma; disseminated neuroblastoma; localized unresectable neuroblastoma; stage 4S neuroblastoma; regional neuroblastoma; untreated childhood medulloblastoma; untreated childhood cerebellar astrocytoma; childhood infratentorial ependymoma; newly diagnosed childhood ependymoma; childhood supratentorial ependymoma; childhood oligodendroglioma; childhood choroid plexus tumor; localized resectable neuroblastoma; childhood low-grade cerebral astrocytoma; untreated childhood supratentorial primitive neuroectodermal tumor
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroectodermal Tumors, Primitive; Neuroectodermal Tumors, Primitive, Peripheral; Nervous System Neoplasms; Central Nervous System Neoplasms; Neuroblastoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Cyclophosphamide; Carboplatin; Methotrexate; Vincristine
• Other Study ID Numbers: CDR0000454575; CCLG-CNS-9204; EU-20574; CCLG-CNS-1992-04