Radiation Therapy or Combination Chemotherapy in Treating Patients With Clinically or Radiologically Progressive Low-Grade Gliomas (SIOP-LGG-2004)

This study is currently recruiting participants.
Verified June 2012 by Societe Internationale d'Oncologie Pediatrique
Sponsor:
Information provided by (Responsible Party):
Astrid K. Gnekow, Societe Internationale d'Oncologie Pediatrique
ClinicalTrials.gov Identifier:
NCT00276640
First received: January 12, 2006
Last updated: June 15, 2012
Last verified: June 2012

January 12, 2006
June 15, 2012
April 2004
April 2012   (final data collection date for primary outcome measure)
  • Progression-free survival [ Time Frame: week 24, and at 1, 3, and 5 years ] [ Designated as safety issue: No ]
  • Event-free survival [ Time Frame: week 24 and at 1, 3, and 5 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: week 24 and at 1, 3, and 5 years ] [ Designated as safety issue: No ]
Not Provided
Complete list of historical versions of study NCT00276640 on ClinicalTrials.gov Archive Site
Response week 24 [ Time Frame: week 24 ] [ Designated as safety issue: No ]
radiological response to therapy (chemotherapy or radiation therapy)
Not Provided
Not Provided
Not Provided
 
Radiation Therapy or Combination Chemotherapy in Treating Patients With Clinically or Radiologically Progressive Low-Grade Gliomas
Cooperative Multicenter Study for Children and Adolescents With Low Grade Glioma

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. 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.

PURPOSE: This clinical trial is studying giving radiation therapy or combination chemotherapy to see how well it works in treating patients with clinically or radiologically progressive low-grade gliomas.

OBJECTIVES:

  • Provide a comprehensive treatment strategy for children and adolescents with low-grade glioma of all tumour locations and histologies.
  • Provide standardized treatment indication and treatment recommendations for non-surgical therapy in children and adolescents with low grade glioma without and with associated neurofibrosis-type 1 (NF1) at diagnosis or after observation.
  • Determine overall, event-free, and progression-free survival.
  • Radiotherapy arm: a. Determine progression free survival in older children without NF1 treated with radiotherapy using modern techniques for planning and treatment. b. Determine the reduction of the rate and intensity of possible late effects of therapy to the organs at risk by optimized planning and treatment.
  • Chemotherapy arm: a. Determine progression free survival for younger children without NF1 treated with chemotherapy and randomized to either the 2-drug or the 3-drug induction regimen. b. Determine the distribution of response at week 24 (after induction) for younger children without NF1 treated with chemotherapy and randomized to either the 2-drug or the 3-drug induction regimen. c. Determine progression free survival for children with NF1treated with chemotherapy.
  • Determine the influence of clinical and histological findings on overall survival, progression-free and event-free survival in these patients.
  • Determine prospectively the late effects of tumor and therapy in these patients.

OUTLINE: This is a partially randomized, open-label, multicenter study.

Children with completely resected tumors, incompletely resected tumors, or those with clinically/neuroradiologically diagnosed tumors, who do not have severe symptoms at diagnosis, are only observed during follow-up.

Children with unresectable/incompletely-resectable tumors, or those with relapsed disease and those observed following incomplete initial resection or neuroradiologic diagnosis and clinical and/or neuro-radiologic progression receive non-surgical therapy. This non-surgical therapy is either chemotherapy (for children younger than 8 years and those with neurofibrosis-type 1 [NF1]) or radiotherapy (for children older than 8 years).

  • Chemotherapy: Within the chemotherapy arm, patients without NF1 are randomized to receive 1 of 2 induction chemotherapy regimens. Patients with NF1 receive the two-drug induction therapy as in arm I.

    • Arm I (two-drug induction therapy [vincristine-carboplatin] ): Patients receive induction therapy comprising vincristine IV on day 1 of weeks 1-10 and weeks 13, 17, and 21 and carboplatin IV over 1 hour on day 1 of weeks 1, 4, 7, 10, 13, 17, and 21.
    • Arm II (three-drug induction therapy [vincristine-carboplatin-etoposide]): Patients receive vincristine and carboplatin as in two-drug induction therapy. Patients also receive etoposide IV over 1 hour on days 1-3 of weeks 1, 4, 7, and 10.

Beginning in week 25, all patients in the chemotherapy arm receive consolidation therapy comprising vincristine IV on days 1, 8, and 15 and carboplatin IV over 1 hour on day 1. Treatment repeats every 6 weeks for 9 courses. Patients experiencing disease progression or an allergic reaction to carboplatin receive vincristine IV on days 1, 8, and 15 and either cyclophosphamide IV over 1 hour on day 1 or cisplatin IV over 3 hours on days 1 and 2. Treatment repeats every 6 weeks for 5 courses. All patients in the chemotherapy arm receive a total of 18 months of treatment.

  • Radiotherapy: Conventional external beam fractionated radiotherapy is given at standard doses for children receiving radiotherapy. Brachytherapy can be given, if tumors are suitable for this type of treatment.

After completion of study treatment, patients are followed periodically for 10 years.

PROJECTED ACCRUAL: A total of 520 patients will be accrued for the randomized arm of this study.

Interventional
Not Provided
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Brain and Central Nervous System Tumors
  • Drug: vincristine, carboplatin

    vincristine: 1,5 mg/m² i.v., week 1,2,3,4,5,6,7,8,9,10,13,17,21

    carboplatin: 550 mg/m² i.v., week 1,4,7,10,13,17,21

  • Drug: vincristine, carboplatin, etoposide

    vincristine: 1,5 mg/m² i.v., week 1,2,3,4,5,6,7,8,9,10,13,17,21

    carboplatin: 550 mg/m² i.v., week 1,4,7,10,13,17,21

    etoposide: 100 mg/m² i.v., week 1,4,7,10

  • Radiation: radiation therapy

    intracranial tumor site: 30 fractions, dose per fraction: 1.8 Gy, total dose: 54 Gy, duration 6 weeks

    spinal tumor site: 28 fractions, dose per fraction: 1.8 Gy, total dose: 50.4 Gy duration 5 1/2 weeks

  • Active Comparator: vincristine, carboplatin
    standard chemotherapy group
    Intervention: Drug: vincristine, carboplatin
  • Active Comparator: vincristine, carboplatin, etoposide
    intensified induction chemotherapy group
    Intervention: Drug: vincristine, carboplatin, etoposide
  • Active Comparator: radiation
    radiation therapy group
    Intervention: Radiation: radiation therapy
  • No Intervention: Control
    Control group: wait and see strategy
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
3000
March 2014
April 2012   (final data collection date for primary outcome measure)

DISEASE CHARACTERISTICS:

  • Histologically confirmed low-grade glioma, of 1 of the following histologic subtypes:

    • Pilocytic astrocytoma I° and variants
    • Subependymal giant cell astrocytoma I°
    • Dysembryoplastic neuroepithelial tumor I°
    • Desmoplastic infantile ganglioglioma I°
    • Ganglioglioma I° and II°
    • Pleomorphic xanthoastrocytoma II°
    • Oligodendroglioma II°
    • Oligoastrocytoma II°
    • Astrocytoma II°

      • Fibrillary astrocytoma II°
      • Protoplasmatic astrocytoma II°
      • Gemistocytic astrocytoma II°
  • Children with chiasmatic-hypothalamic tumors may be eligible without histological diagnosis, if neuroradiologic findings meet unequivocal criteria for the presence of a low-grade glioma
  • Primary tumor localization: intracranial and/or spinal cord

    • No diffuse intrinsic tumors of the pons, even if histologically an astrocytoma I° or II° is diagnosed

      • Exception: pontine glioma II° in neurofibromatosis type 1 (NF1) disease allowed
  • Children presenting with disseminated low-grade glioma will be eligible for the study
  • All eligible patients without NF1 disease receiving chemotherapy as their first nonsurgical therapy are eligible for randomization
  • Children are eligible for the trial regardless of the presence of associated genetic disease: NF1 disease will be the prominent one, all children with NF1 disease are entered into the study arm III in case of an indication for nonsurgical therapy
  • Patients presenting with rare intracranial neoplasms of low-grade malignancy, but nonglial origin, may be followed according to the low-grade glioma strategy, but they are not subject of this therapy trial.

    • Data from these patients may be registered to learn about those therapeutic interventions which may prove useful to these patients and to develop separate strategies in the future
    • Patients with choroid plexus papilloma should be entered into the SIOP-CPT study (Prof. Dr. J. Wolff, M.D. Anderson Cancer Center, Houston, Texas)

PATIENT CHARACTERISTICS:

  • No preexisting impairments of health status, making the conduct of the study impossible or ethically unwise
  • No evidence of pregnancy or lactation period
  • Pregnancy has to be prevented in fertile adolescent girls during chemotherapy by reliable contraception methods (e.g., hormonal contraception)

PRIOR CONCURRENT THERAPY:

  • The tumor should not be pretreated with chemotherapy or radiotherapy

    • Children treated with chemotherapy or radiotherapy prior to entering the study will be evaluated separately

      • Previous treatment with steroids is not considered a chemotherapeutic treatment
  • Surgery of any type and extent allowed

    • Prior surgical resection of the tumor allowed
  • Participation in another clinical study concurrently with this study (e.g., endocrinologic study) allowed provided it is not interfering with the present treatment strategy
  • No other concurrent chemotherapy
  • Concurrent medication for associated or other conditions (e.g., hormone replacement, anticonvulsants) that does not containing cytostatic drugs allowed
Both
up to 18 Years
No
Not Provided
Austria,   Belgium,   Croatia,   Denmark,   France,   Germany,   Italy,   Norway,   Poland,   Portugal,   Switzerland,   United Kingdom
 
NCT00276640
CDR0000454506, 2005-005377-29
Yes
Astrid K. Gnekow, Societe Internationale d'Oncologie Pediatrique
Societe Internationale d'Oncologie Pediatrique
Not Provided
Study Chair: Astrid Gnekow Klinikum Augsburg
Societe Internationale d'Oncologie Pediatrique
June 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP