Clinical trial NCT00281905: Combination Chemotherapy With or Without Radiation Therapy in Treating Children With Brain Tumors
Official title: Management of Children Aged Less Than 3 Years With Brain Tumors
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Brain and Central Nervous System Tumors
Neuroblastoma
Keywords: untreated childhood brain stem glioma
childhood high-grade cerebral astrocytoma
childhood low-grade cerebral astrocytoma
untreated childhood cerebellar astrocytoma
childhood choroid plexus tumor
childhood infratentorial ependymoma
childhood supratentorial ependymoma
newly diagnosed childhood ependymoma
untreated childhood medulloblastoma
childhood oligodendroglioma
untreated childhood supratentorial primitive neuroectodermal tumor
disseminated neuroblastoma
localized resectable neuroblastoma
localized unresectable neuroblastoma
regional neuroblastoma
stage 4S neuroblastoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2006-01-25
Enrollment: 50
Sex: ALL
Maximum age (years): 3
Standard ages: CHILD
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Response rate
measure: Event-free survival
measure: Local recurrence or occurrence of CNS metastases
measure: Quality of survival
measure: Tolerance
measure: Long-term toxicity
measure: Proportion of patients requiring radiotherapy
measure: Prognosis of children who receive both chemotherapy and radiotherapy
measure: Nature and behavior of brain tumors
Secondary outcomes:
Other outcomes:
Locations:
city: Dublin
country: Ireland
facility: Our Lady's Hospital for Sick Children
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: 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: Royal London 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 General Hospital
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: Queen's Medical Center
name: Richard Grundy, MD, PhD
role: STUDY_CHAIR
References: