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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2012 by Societe Internationale d'Oncologie Pediatrique.
Recruitment status was  Recruiting
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
  Purpose

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.


Condition Intervention
Brain and Central Nervous System Tumors
Drug: vincristine, carboplatin
Drug: vincristine, carboplatin, etoposide
Radiation: radiation therapy

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Cooperative Multicenter Study for Children and Adolescents With Low Grade Glioma

Resource links provided by NLM:


Further study details as provided by Societe Internationale d'Oncologie Pediatrique:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • Response week 24 [ Time Frame: week 24 ] [ Designated as safety issue: No ]
    radiological response to therapy (chemotherapy or radiation therapy)


Estimated Enrollment: 3000
Study Start Date: April 2004
Estimated Study Completion Date: March 2014
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: vincristine, carboplatin
standard chemotherapy group
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

Active Comparator: vincristine, carboplatin, etoposide
intensified induction chemotherapy group
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

Active Comparator: radiation
radiation therapy group
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

No Intervention: Control
Control group: wait and see strategy

  Hide Detailed Description

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   up to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00276640

Locations
Austria
Allg. Krankenhaus der Stadt Wien Universitaets-Kinderklinik Recruiting
Wien, Austria, 1090
Contact: Irene Slavc    43-140-400-3175      
Belgium
Universitair Ziekenhuis Gent Recruiting
Ghent, Belgium, B-9000
Contact: Joris Verlooy, MD    32-9-240-3579    joris.verlooy@ugent.be   
Croatia
Children's Hospital Zagreb Recruiting
Zagreb, Croatia, 10000
Contact: Jasminka Stepan    385-1-460-0202      
Denmark
Aalborg Hospital Recruiting
Aalborg, Denmark, 9100
Contact: Jon Helgestad, MD    45-9932-1312      
France
Institut Gustave Roussy Recruiting
Villejuif, France, F-94805
Contact: Jacques Grill, MD, PhD    33-1-4211-6209      
Germany
Klinikum Augsburg Recruiting
Augsburg, Germany, DOH-86156
Contact: Astrid Gnekow    49-821-400-3603      
Italy
Azienda Ospedaliera di Padova Recruiting
Padova, Italy, 35128
Contact: Giorgio Perilongo, MD    39-49-821-2105    perilong@child.pedi.unipd.it   
Norway
University of Tromso Recruiting
Tromso, Norway, N-9037
Contact: Tore Stokland    47-7762-6000      
Poland
Children's Memorial Health Institute Recruiting
Warsaw, Poland, 04-736
Contact: Marta Perek-Polnik    48-22-815-7000      
Portugal
Hospital San Joao Recruiting
Porto, Portugal, 4200
Contact: Maria J. Gil-Da-Costa, MD    351-222-551-2100 ext. 1671    mj.gil_da_costa@netcabo.pt   
Switzerland
University Children's Hospital Recruiting
Zurich, Switzerland, CH-8032
Contact: Michael Grotzer, MD    41-44-266-7111    michael.grotzer@kispi.unizh.ch   
United Kingdom
Leeds Cancer Centre at St. James's University Hospital Recruiting
Leeds, England, United Kingdom, LS9 7TF
Contact: Susan V. Picton, MD    44-11-32-064-985      
Queen's Medical Centre Recruiting
Nottingham, England, United Kingdom, NG7 2UH
Contact: David A. Walker    44-115-924-9924 ext 61727    david.walker@nottingham.ac.uk   
Sponsors and Collaborators
Societe Internationale d'Oncologie Pediatrique
Investigators
Study Chair: Astrid Gnekow Klinikum Augsburg
  More Information

Additional Information:
No publications provided

Responsible Party: Astrid K. Gnekow, Chairlady, Societe Internationale d'Oncologie Pediatrique
ClinicalTrials.gov Identifier: NCT00276640     History of Changes
Other Study ID Numbers: CDR0000454506, 2005-005377-29
Study First Received: January 12, 2006
Last Updated: June 15, 2012
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Societe Internationale d'Oncologie Pediatrique:
recurrent childhood brain stem glioma
untreated childhood brain stem glioma
recurrent childhood cerebellar astrocytoma
untreated childhood cerebellar astrocytoma
childhood low-grade cerebral astrocytoma
recurrent childhood cerebral astrocytoma
childhood oligodendroglioma
recurrent childhood visual pathway and hypothalamic glioma
untreated childhood visual pathway and hypothalamic glioma
childhood spinal cord neoplasm

Additional relevant MeSH terms:
Glioma
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms by Site
Nervous System Diseases
Etoposide
Vincristine
Etoposide phosphate
Carboplatin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 24, 2014