Combination Chemotherapy Followed By Peripheral Stem Cell Transplant in Treating Young Patients With Newly Diagnosed Supratentorial Primitive Neuroectodermal Tumors or High-Risk Medulloblastoma - Full Text View

Sponsors and Collaborators:	Children's Oncology Group National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00336024

Purpose

RATIONALE: 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. Giving more than one drug (combination chemotherapy) together with a peripheral stem cell transplant may allow more chemotherapy to be given so that more tumor cells are killed. It is not yet known which combination chemotherapy regimen is more effective when given before a peripheral stem cell transplant in treating supratentorial primitive neuroectodermal tumors or medulloblastoma.

PURPOSE: This randomized phase III trial is studying two different combination chemotherapy regimens to compare how well they work when given before a peripheral stem cell transplant in treating young patients with newly diagnosed supratentorial primitive neuroectodermal tumors or high-risk medulloblastoma .

Condition	Intervention	Phase
Brain and Central Nervous System Tumors	Drug: carboplatin Drug: cisplatin Drug: cyclophosphamide Drug: etoposide Drug: leucovorin calcium Drug: methotrexate Drug: thiotepa Drug: vincristine sulfate	Phase III

MedlinePlus related topics: Cancer

Drug Information available for: Cyclophosphamide Carboplatin Etoposide Leucovorin Calcium Citrovorum factor Folinic acid calcium salt pentahydrate Leucovorin Methotrexate Vincristine sulfate Vincristine Cisplatin Thiotepa Etoposide phosphate Calcium gluconate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized
Official Title:	A Phase III Randomized Trial for the Treatment of Newly Diagnosed Supratentorial PNET and High Risk Medulloblastoma in Children <36 Months Old With Intensive Induction Chemotherapy With Methotrexate Followed by Consolidation With Stem Cell Rescue Versus the Same Therapy Without Methotrexate

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

Primary Outcome Measures:

Complete response by 3-dimensional tumor measurements [ Designated as safety issue: No ]

Secondary Outcome Measures:

Time to treatment failure [ Designated as safety issue: No ]

Estimated Enrollment:	96
Study Start Date:	August 2007
Estimated Primary Completion Date:	August 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Induction therapy arm I: Active Comparator Patients receive vincristine IV on days 1, 8, and 15; etoposide IV over 1 hour on days 1-3; cyclophosphamide IV over 1 hour on days 1 and 2; cisplatin IV over 6 hours on day 3. Treatment repeats every 3 weeks for 3 courses.	Drug: carboplatin Given IV Drug: cisplatin Given IV Drug: cyclophosphamide Given IV Drug: etoposide Given IV Drug: thiotepa Given IV Drug: vincristine sulfate Given IV
Induction therapy arm II: Experimental Patients receive vincristine IV on days 1, 8, and 15; high-dose methotrexate IV over 4 hours on day 1; and leucovorin calcium IV or orally every 6 hours beginning on day 2 and continuing until methotrexate levels are in a safe range. Once methotrexate levels are in a safe range, patients then receive etoposide IV over 1 hour on approximately days 4, 5, and 6, cyclophosphamide IV over 1 hour on approximately days 4 and 5, and cisplatin IV over 6 hours on approximately day 6. Treatment repeats every 3 weeks for 3 courses.	Drug: carboplatin Given IV Drug: cisplatin Given IV Drug: cyclophosphamide Given IV Drug: etoposide Given IV Drug: leucovorin calcium Given IV Drug: methotrexate Given IV Drug: thiotepa Given IV Drug: vincristine sulfate Given IV

Arms

Assigned Interventions

Induction therapy arm I: Active Comparator

Patients receive vincristine IV on days 1, 8, and 15; etoposide IV over 1 hour on days 1-3; cyclophosphamide IV over 1 hour on days 1 and 2; cisplatin IV over 6 hours on day 3. Treatment repeats every 3 weeks for 3 courses.

Drug: carboplatin

Given IV

Drug: cisplatin

Given IV

Drug: cyclophosphamide

Given IV

Drug: etoposide

Given IV

Drug: thiotepa

Given IV

Drug: vincristine sulfate

Given IV

Induction therapy arm II: Experimental

Patients receive vincristine IV on days 1, 8, and 15; high-dose methotrexate IV over 4 hours on day 1; and leucovorin calcium IV or orally every 6 hours beginning on day 2 and continuing until methotrexate levels are in a safe range. Once methotrexate levels are in a safe range, patients then receive etoposide IV over 1 hour on approximately days 4, 5, and 6, cyclophosphamide IV over 1 hour on approximately days 4 and 5, and cisplatin IV over 6 hours on approximately day 6. Treatment repeats every 3 weeks for 3 courses.

Drug: carboplatin

Given IV

Drug: cisplatin

Given IV

Drug: cyclophosphamide

Given IV

Drug: etoposide

Given IV

Drug: leucovorin calcium

Given IV

Drug: methotrexate

Given IV

Drug: thiotepa

Given IV

Drug: vincristine sulfate

Given IV

Show Detailed Description

Eligibility

Ages Eligible for Study:	up to 2 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of 1 of the following:
- High-risk medulloblastoma defined by any of the following:
  - Residual disease > 1.5 cm²
  - Lumbar cerebral spinal fluid cytology positive for tumor cells by analysis of fluid collected either before definitive surgery or ≥ 10 days after definitive surgery unless contraindicated
  - M0 disease in children < 8 months of age at diagnosis
  - M2 or M3 metastatic disease by MRI
  - M4 disease
- Supratentorial primitive neuroectodermal tumor (PNET)
MRI evidence of spinal disease
Tumor must be negative for INI1 gene
Has undergone definitive surgery within the past 31 days
No atypical teratoid rhabdoid tumors
Biological specimens must be available for correlative laboratory studies

PATIENT CHARACTERISTICS:

Life expectancy > 8 weeks
Creatinine clearance or radioisotope glomerular filtration rate ≥ 60 mL/min
Bilirubin ≤ 1.5 times upper limit of normal (ULN)
AST and ALT < 2 times ULN
Shortening fraction ≥ 27% by echocardiogram
Ejection fraction ≥ 47% by radionuclide angiogram
No evidence of dyspnea at rest
Pulse oximetry > 94% on room air
Absolute neutrophil count > 1,000/mm³
Platelet count > 100,000/mm³ (transfusion independent)
Hemoglobin > 8 g/dL (RBC transfusions allowed)

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
No prior radiation therapy or chemotherapy
Prior corticosteroids allowed

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00336024

Show 90 Study Locations

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:	Claire Mazewski, MD	AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Scottish Rite Campus
Investigator:	Stewart J. Kellie, MD	Children's Hospital at Westmead

More Information

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

Study ID Numbers:	CDR0000483683, COG-ACNS0334
Study First Received:	June 8, 2006
Last Updated:	January 2, 2009
ClinicalTrials.gov Identifier:	NCT00336024
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

untreated childhood medulloblastoma
untreated childhood supratentorial primitive neuroectodermal tumor

Study placed in the following topic categories:

Neuroectodermal Tumors, Primitive
Leucovorin
Vincristine
Carboplatin
Central Nervous System Neoplasms
Cyclophosphamide
Etoposide phosphate
Thiotepa
Folic Acid
Calcium, Dietary

Neuroectodermal Tumors
Cisplatin
Neoplasms, Germ Cell and Embryonal
Medulloblastoma
Neuroepithelioma
Methotrexate
Glioma
Etoposide
Nervous System Neoplasms
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Neoplasms, Nerve Tissue
Reproductive Control Agents
Neoplasms by Site
Therapeutic Uses
Vitamins
Abortifacient Agents
Micronutrients
Dermatologic Agents
Alkylating Agents

Nucleic Acid Synthesis Inhibitors
Neoplasms by Histologic Type
Vitamin B Complex
Growth Substances
Mitosis Modulators
Nervous System Diseases
Enzyme Inhibitors
Antimitotic Agents
Folic Acid Antagonists
Abortifacient Agents, Nonsteroidal
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Tubulin Modulators
Myeloablative Agonists

ClinicalTrials.gov processed this record on January 16, 2009