Chemotherapy, Radiation Therapy, and Peripheral Stem Cell Transplantation in Treating Children With Newly Diagnosed Medulloblastoma or Supratentorial Primitive Neuroectodermal Tumor
Information source: National Cancer Institute (NCI)
Information obtained from ClinicalTrials.gov on May 08, 2007
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Brain and Central Nervous System Tumors
Intervention: amifostine trihydrate (Drug); cisplatin (Drug); cyclophosphamide (Drug); filgrastim (Drug); vincristine (Drug); biological therapy (Procedure); bone marrow ablation with stem cell support (Procedure); chemoprotection (Procedure); chemotherapy (Procedure); colony-stimulating factor therapy (Procedure); cytokine therapy (Procedure); peripheral blood stem cell transplantation (Procedure); radiation therapy (Procedure); radioprotection (Procedure); supportive care/therapy (Procedure)
Phase: Phase 2
Status: No longer recruiting
Sponsored by: St. Jude Children's Research Hospital Official(s) and/or principal investigator(s):
Amar Gajjar, MD, Study Chair, Affiliation: St. Jude Children's Research Hospital
Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy and radiation therapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy or radiation therapy and kill more tumor cells.
PURPOSE: Phase II trial to study the effectiveness of chemotherapy with topotecan, cyclophosphamide, cisplatin, and vincristine plus radiation therapy and peripheral stem cell transplantation in treating children with newly diagnosed medulloblastoma or supratentorial primitive neuroectodermal tumor.
Clinical Details
Official title:
Treatment of Newly Diagnosed Medulloblastoma and Supratentorial PNET in Patients At Least 3 Years With a Phase II Topotecan Window (High-Risk Patients Only), Risk-Adapted Radiation Therapy, and Dose-Intensive Chemotherapy With Peripheral Blood Stem Cell Support
Study design: Interventional, Supportive Care
Detailed description:
OBJECTIVES:
* Estimate the response rate to topotecan in children with newly diagnosed medulloblastoma or supratentorial primitive neuroectodermal tumors who have measurable residual disease after surgery. (Topotecan window closed to accrual 9/10/2001)
* Determine the feasibility of four courses of high-dose chemotherapy (vincristine, cisplatin, and cyclophosphamide) with peripheral blood stem cell support after craniospinal irradiation (CSI) in these patients.
* Estimate the 5-year overall survival and progression-free survival in patients treated with risk-adapted CSI and high-dose chemotherapy.
* Compare changes in intellectual functioning in patients treated with reduced-dose vs standard-dose CSI.
* Estimate the incidence of ototoxicity associated with risk-adapted CSI and posterior fossa boost(s) given by 3-D conformal radiotherapy technique combined with amifostine and cisplatin.
* Evaluate the relationship between amifostine and WR1065 plasma systemic exposure and pharmacologic effect (e. g., toxicity and reduction in cisplatin-induced ototoxicity).
OUTLINE: This is a multicenter study. Patients are assigned to 1 of 2 treatment groups based on risk status.
* Group 1 (average-risk): Patients receive filgrastim (G-CSF) subcutaneously (SC) or IV daily until peripheral blood stem cells (PBSC) are harvested. PBSC are harvested when blood counts recover. Patients then receive craniospinal irradiation (CSI) 5 days a week for 6 weeks. Beginning 6 weeks after completion of CSI, patients receive high-dose chemotherapy comprising vincristine IV followed by cisplatin IV over 6 hours on day - 4 and cyclophosphamide IV over 1 hour on days -3 and -2. Patients receive amifostine IV over 1 minute a maximum of 5 minutes prior to cisplatin infusion and then 3 hours into cisplatin infusion. PBSC are reinfused on day 0. Patients receive G-CSF SC beginning on day 1 and continuing for a minimum of 7 days or until blood counts recover. Vincristine IV is administered on day 6. G-CSF is stopped 48 hours prior to beginning subsequent courses of chemotherapy. High-dose chemotherapy repeats every 4 weeks for 4 courses.
* Group 2 (high-risk): Patients receive topotecan IV over 4 hours on days 1-5 and G-CSF SC or IV beginning 24 hours after completion of the first course of topotecan and continuing until PBSC are harvested. Treatment repeats every 3 weeks for 2 courses. If an adequate number of PBSC are not harvested, the patient undergoes a second harvest of PBSC after the second course of topotecan. Patients then receive CSI, high-dose chemotherapy, amifostine, and PBSC support as in group 1. (Topotecan window closed to accrual 9/10/2001) Patients undergo neuropsychological testing prior to radiotherapy and chemotherapy and then at 1, 2, and 5 years.
Patients are followed at 1, 2, 4, 6, 9, 12, 15, 18, and 24 months and then every 6 months for 3 years.
PROJECTED ACCRUAL: A total of 12-36 patients will be accrued for this study within 5 years.
Eligibility
Minimum age: 3 Years.
Maximum age: 20 Years.
Gender(s): Both.
Criteria:
DISEASE CHARACTERISTICS:
* Histologically proven medulloblastoma or supratentorial primitive neuroectodermal tumor
* Average-risk group:
- Localized tumor with no overt evidence of invasion beyond the posterior fossa
- Less than 1. 5 cm2 residual tumor/imaging abnormality
- No CNS or extraneural metastasis (confirmed by bone scan)
- Brain stem invasion allowed if above criteria met
* High-risk group:
- Metastatic disease within the neuraxis (subarachnoid dissemination) OR greater than 1. 5 cm^2 residual disease at the primary site after surgery
* No bone involvement by bone scan
* Must begin study within 28 days of definitive surgery
PATIENT CHARACTERISTICS:
Age
* 3 to 20 at diagnosis
Performance status
* ECOG 0-3 (except patients with posterior fossa syndrome)
Life expectancy
* Not specified
Hematopoietic
* WBC greater than 3,000/mm^3
* Absolute neutrophil count greater than 1,500/mm^3
* Platelet count greater than 100,000/mm^3
* Hemoglobin greater than 10 g/dL
Hepatic
* Bilirubin less than 1. 5 mg/dL
* SGPT less than 1. 5 times normal
Renal
* Creatinine less than 1. 2 mg/dL OR
* Creatinine clearance greater than 70 mL/min
Other
* Not pregnant or nursing
* Negative pregnancy test
* HIV negative
PRIOR CONCURRENT THERAPY:
Biologic therapy
* Not specified
Chemotherapy
* No prior chemotherapy
Endocrine therapy
* Prior corticosteroids allowed
Radiotherapy
* No prior radiotherapy
Surgery
* See Disease Characteristics
Locations and Contacts
Children's Hospital at Westmead, Westmead, New South Wales 2145, Australia
Texas Children's Cancer Center, Houston, Texas 77030-2399, United States
Royal Children's Hospital, Parkville, Victoria 3052, Australia
Additional Information
Clinical trial summary from the National Cancer Institute's PDQ® database
Related publications: Gajjar A, Chintagumpala M, Ashley D, Kellie S, Kun LE, Merchant TE, Woo S, Wheeler G, Ahern V, Krasin MJ, Fouladi M, Broniscer A, Krance R, Hale GA, Stewart CF, Dauser R, Sanford RA, Fuller C, Lau C, Boyett JM, Wallace D, Gilbertson RJ. Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed medulloblastoma (St Jude Medulloblastoma-96): long-term results from a prospective, multicentre trial. Lancet Oncol. 2006 Oct;7(10):813-20. Erratum in: Lancet Oncol. 2006 Oct;7(10):797.
Last updated: February 20, 2007
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