A Phase III Randomized Trial for the Treatment of Pediatric High Grade Gliomas at First Recurrence With a Single High Dose Chemotherapy and Autologous Stem Cell Transplant Versus Three Courses of Intermediate Dose Chemotherapy With Peripheral Blood Stem Cell (PBSC) Support
filgrastim
+ carboplatin
+ etoposide
Astrocytome+13
+ Maladies du cerveau
+ Néoplasmes cérébraux
Étude thérapeutique
Résumé
Date de début de l'étude : 1 octobre 2004
Date à laquelle le premier participant a commencé l'étude.OBJECTIVES: * Compare the event-free survival and overall survival of pediatric patients with recurrent high-grade gliomas treated with a single course of high-dose carboplatin, etoposide, and thiotepa and autologous stem cell transplantation vs multiple courses of intermediate-dose carboplatin and thiotepa and autologous stem cell transplantation with or without isotretinoin. * Compare the number of hospital days and time to engraftment in patients treated with these regimens. * Compare the toxic death rate in patients treated with these regimens. * Compare the tolerability of isotretinoin in patients treated with these regimens. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to pathologic diagnosis (glioblastoma multiforme vs anaplastic astrocytoma vs other high-grade glioma). * Chemotherapy and autologous stem cell reinfusion (ASCR): Patients are randomized to 1 of 2 treatment arms. * Arm I (high-dose chemotherapy and ASCR): Patients receive high-dose chemotherapy comprising carboplatin IV over 4 hours on days -8 to -6; thiotepa IV over 3 hours and etoposide IV over 3 hours on days -5 to -3; and filgrastim (G-CSF) IV or subcutaneously (SC) once daily beginning on day 1 and continuing until blood counts recover. Autologous peripheral blood stem cells (PBSC) or bone marrow are reinfused on day 0. * Arm II (intermediate-dose chemotherapy and ASCR): Patients receive intermediate-dose chemotherapy comprising carboplatin IV over 4 hours and thiotepa IV over 3 hours on days 1-2 and G-CSF IV or SC once daily beginning on day 4 and continuing until blood counts recover. Autologous PBSC or bone marrow are reinfused on day 3. Treatment repeats every 28 days for a total of 3 courses. * Maintenance therapy: After recovery from chemotherapy (approximately day 30 post-transplantation), all patients are further randomized to 1 of 2 maintenance arms. * Arm I: Patients receive oral isotretinoin twice daily on days 1-14. Treatment repeats every 28 days for a total of 6 courses. * Arm II: Patients do not receive maintenance therapy. In all arms, treatment continues in the absence of disease progression. Patients are followed every 3 months for 1 year, every 6 months for 3 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 80-150 patients (40-75 per treatment arm) will be accrued for this study within 5 years.
Protocole
Cette section fournit des détails sur le plan de l'étude, y compris la manière dont l'étude est conçue et ce qu'elle évalue.1 participant à inclure
Nombre total de participants que l'essai clinique vise à recruter.Traitement
Éligibilité
Les chercheurs recherchent des patients correspondant à une certaine description appelée critères d'éligibilité : état de santé général ou traitements antérieurs du patient.Tout sexe
Le sexe biologique des participants éligibles à s'inscrire.Jusqu'à 20 ans
Tranche d'âge des participants éligibles à participer.Volontaires sains non autorisés
Indique si les individus en bonne santé et ne présentant pas la condition étudiée peuvent participer.Conditions
Pathologie
Critères
DISEASE CHARACTERISTICS: * Histologically confirmed diagnosis of 1 of the following high-grade gliomas: * Glioblastoma multiforme * Anaplastic astrocytoma * Gliosarcoma * Disease in first relapse * No primary brainstem or spinal cord gliomas * No secondary glioblastomas arising after prior treatment for a non-glial tumor * Prior local radiotherapy of 5,000-6,000 cGy required * Less than 1.5 cm of residual gadolinium-enhancing tumor in maximal cross-sectional diameter by MRI * No metastatic tumor by spinal MRI PATIENT CHARACTERISTICS: Age * Under 21 at diagnosis Performance status * Lansky 50-100% OR * Karnofsky 50-100% Life expectancy * Not specified Hematopoietic * Absolute neutrophil count ≥ 500/mm\^3 * Platelet count ≥ 100,000/mm\^3 (transfusion independent) Hepatic * Bilirubin ≤ 1.5 times upper limit of normal (ULN) * AST or ALT \< 2.5 times ULN Renal * Glomerular filtration rate ≥ 60 mL/min AND/OR * Creatinine clearance ≥ 60 mL/min Cardiovascular * Shortening fraction ≥ 27% by echocardiogram OR * Ejection fraction ≥ 50% by MUGA Pulmonary * No dyspnea at rest * No exercise intolerance * Pulse oximetry \> 94% Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy * Not specified Chemotherapy * More than 4 weeks since prior chemotherapy * No prior thiotepa * No prior myeloablative chemotherapy Endocrine therapy * No concurrent corticosteroids Radiotherapy * See Disease Characteristics * More than 8 weeks since prior radiotherapy * No prior craniospinal radiotherapy Surgery * Not specified
Plan de l'étude
Découvrez tous les traitements administrés dans cette étude, leur description détaillée et ce qu'ils impliquent.3 groupes d'intervention sont désignés dans cette étude
Cette étude ne comporte pas de groupe placebo.
Groupes de traitement
Groupe I
ExpérimentalGroupe II
ExpérimentalGroupe III
ExpérimentalObjectifs de l'étude
Objectifs principaux
Objectifs secondaires
Centres d'étude
Ce sont les hôpitaux, cliniques ou centres de recherche où l'essai est conduit. Vous pouvez trouver le site le plus proche de vous ainsi que son statut.Cette étude comporte 59 sites
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
Little Rock, United StatesOuvrir Arkansas Cancer Research Center at University of Arkansas for Medical Sciences dans Google MapsChildren's Hospital and Research Center - Oakland
Oakland, United StatesUniversity of California Davis Cancer Center
Sacramento, United StatesChildren's Hospital and Health Center - San Diego
San Diego, United States