Chemotherapy, Radiation Therapy, and Peripheral Stem Cell Transplantation in Treating Children With Newly Diagnosed Medulloblastoma or Supratentorial Primitive Neuroectodermal Tumor - Full Text View

Sponsor:	St. Jude Children's Research Hospital
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00003211

Purpose

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.

Condition	Intervention	Phase
Brain and Central Nervous System Tumors	Biological: filgrastim Drug: amifostine trihydrate Drug: cisplatin Drug: cyclophosphamide Drug: vincristine sulfate Procedure: peripheral blood stem cell transplantation Radiation: radiation therapy	Phase II

Study Type:	Interventional
Study Design:	Supportive Care
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Cyclophosphamide Vincristine Cisplatin Amifostine Filgrastim Vincristine sulfate

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Study Start Date:

October 1996

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

Ages Eligible for Study:	3 Years to 20 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003211

Locations

United States, Texas
Texas Children's Cancer Center
Houston, Texas, United States, 77030-2399
Australia, New South Wales
Children's Hospital at Westmead
Westmead, New South Wales, Australia, 2145
Australia, Victoria
Royal Children's Hospital
Parkville, Victoria, Australia, 3052

Sponsors and Collaborators

St. Jude Children's Research Hospital

National Cancer Institute (NCI)

Investigators

Study Chair:

Amar Gajjar, MD

St. Jude Children's Research Hospital

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Laughton SJ, Merchant TE, Sklar CA, Kun LE, Fouladi M, Broniscer A, Morris EB, Sanders RP, Krasin MJ, Shelso J, Xiong Z, Wallace D, Gajjar A. Endocrine outcomes for children with embryonal brain tumors after risk-adapted craniospinal and conformal primary-site irradiation and high-dose chemotherapy with stem-cell rescue on the SJMB-96 trial. J Clin Oncol. 2008 Mar 1;26(7):1112-8.

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.

Study ID Numbers:	CDR0000066069, SJCRH-MB-96, SJMB-96, NCI-G98-1387
Study First Received:	November 1, 1999
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00003211 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

untreated childhood supratentorial primitive neuroectodermal tumor
untreated childhood medulloblastoma

Additional relevant MeSH terms:

Radiation-Protective Agents
Neuroectodermal Tumors, Primitive
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Neoplasms, Nerve Tissue
Physiological Effects of Drugs
Central Nervous System Neoplasms
Cyclophosphamide
Neoplasms by Site
Cisplatin
Neoplasms, Germ Cell and Embryonal
Therapeutic Uses
Glioma
Alkylating Agents

Nervous System Neoplasms
Neoplasms by Histologic Type
Amifostine
Mitosis Modulators
Nervous System Diseases
Vincristine
Antimitotic Agents
Protective Agents
Immunosuppressive Agents
Pharmacologic Actions
Neuroectodermal Tumors
Neoplasms
Radiation-Sensitizing Agents
Tubulin Modulators
Myeloablative Agonists

ClinicalTrials.gov processed this record on November 09, 2009