Radiation Therapy Plus Combination Chemotherapy in Treating Children With Medulloblastoma - Full Text View

Sponsored by:	University Hospitals, Leicester
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00053872

Purpose

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving radiation therapy in different ways with combination chemotherapy may kill any remaining tumor cells following surgery. It is not yet known which radiation therapy regimen combined with combination chemotherapy is more effective in treating medulloblastoma.

PURPOSE: Randomized phase III trial to compare different radiation therapy regimens plus combination chemotherapy in treating children who have undergone surgery for medulloblastoma.

Condition	Intervention	Phase
Brain and Central Nervous System Tumors	Drug: cisplatin Drug: lomustine Drug: vincristine sulfate Procedure: adjuvant therapy Procedure: radiation therapy	Phase III

MedlinePlus related topics: Cancer

Drug Information available for: Vincristine sulfate Vincristine Cisplatin Lomustine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
Official Title:	A Prospective Randomised Controlled Trial Of Hyperfractionated Versus Conventionally Fractionated Radiotherapy In Standard Risk Medulloblastoma

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

Primary Outcome Measures:

Comparison of event-free survival at 3 years [ Designated as safety issue: No ]

Secondary Outcome Measures:

Comparison of overall survival [ Designated as safety issue: No ]
Comparison of the pattern of relapse (i.e., local relapse [tumor bed and posterior fossa outside tumor bed]) [ Designated as safety issue: No ]
Comparison of late sequelae, in terms of health status, quality of life, hearing loss, and endocrine deficiencies [ Designated as safety issue: No ]
Toxicity of neurosurgery [ Designated as safety issue: Yes ]

Estimated Enrollment:	316
Study Start Date:	February 2003

Detailed Description:

OBJECTIVES:

Compare the event-free survival rate in pediatric patients with standard-risk medulloblastoma treated with conventional vs hyperfractionated radiotherapy and vincristine followed by maintenance with cisplatin, lomustine, and vincristine.
Compare the overall survival of patients treated with these regimens.
Compare the pattern of relapse, especially local relapse (tumor bed or posterior fossa outside tumor bed), in patients treated with these regimens.
Determine the toxicity of surgery and whether there are identifiable factors that correlate with toxicity in these patients.
Determine the impact of any surgical complications on commencement of adjuvant therapy and event-free survival of these patients.
Compare late sequelae, in terms of health status, endocrine deficiencies, and hearing loss, in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to country. Patients are randomized to 1 of 2 treatment arms.

Arm I: Within 28-40 days after surgical resection, patients undergo conventional fractionated radiotherapy once daily, 5 days a week, for 6-7 weeks. Patients also receive vincristine IV once weekly for 8 weeks.
Arm II: Beginning as in arm I, patients undergo hyperfractionated radiotherapy twice daily, 5 days a week, for 6-7 weeks. Patients also receive vincristine as in arm I.
Maintenance chemotherapy:Six weeks after completion of radiotherapy, all patients receive cisplatin IV over 6 hours and oral lomustine on day 1 and vincristine IV on days 1, 8, and 15. Treatment repeats every 6 weeks for 8 courses.

Patients are followed at least every 6 months for 3 years.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 316 patients (158 per treatment arm) will be accrued for this study within 4 years.

Eligibility

Ages Eligible for Study:	3 Years to 21 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed medulloblastoma, including the following variants:
- Classic
- Nodular/desmoplastic
- Large cell
- Melanotic
- Medullomyoblastoma
Prior total or subtotal surgical removal of tumor within the past 28-40 days
- No more than 1.5 cm^2 residual tumor by early postoperative MRI or CT scan
No brainstem or supratentorial primitive neuroectodermal tumor
No atypical teratoid rhabdoid tumor
No known predisposition to medulloblastoma (e.g., Gorlin's syndrome)
No CNS metastasis (supratentorial, arachnoid of the posterior fossa, or craniospinal axis) by MRI
No clinical evidence of metastasis outside the CNS
No tumor cells in lumbar cerebrospinal fluid by cytospin

PATIENT CHARACTERISTICS:

Age

3 to 21

Performance status

Not specified

Life expectancy

Not specified

Hematopoietic

Hematological function less than CTC grade 2

Hepatic

Liver function less than CTC grade 2

Renal

Renal function less than CTC grade 2

Other

Not pregnant
Fertile patients must use effective contraception
Able to receive radiotherapy twice daily
Vital functions within age-appropriate normal range
Audiological function less than CTC grade 2
No medical contraindication to radiotherapy or chemotherapy

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

Not specified

Endocrine therapy

Concurrent dexamethasone as an antiemetic allowed, provided all other therapies have failed

Radiotherapy

No concurrent cobalt irradiation

Surgery

See Disease Characteristics

Other

No prior treatment for brain tumor or any other malignancy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00053872

Locations

Belgium
U.Z. Gasthuisberg
Leuven, Belgium, B-3000
France
Institut Curie Hopital
Paris, France, 75248
Germany
Universitaets - Kinderklinik Wuerzburg
Wuerzburg, Germany, D-97080
Italy
Ospedale Infantile Regina Margherita
Turin, Italy, 10126
Netherlands
Academisch Medisch Centrum at University of Amsterdam
Amsterdam, Netherlands, 1105 AZ
Spain
Hospital de Cruces
Vizcaya, Spain, 48
Sweden
Ostra Sjukhuset
Gothenburg, Sweden, 41685
United Kingdom, England
Royal Liverpool Children's Hospital, Alder Hey
Liverpool, England, United Kingdom, L12 2AP

Sponsors and Collaborators

University Hospitals, Leicester

Investigators

Study Chair:

Brigitta Lannering, MD, PhD

Ostra Sjukhuset

More Information

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

Study ID Numbers:	CDR0000269521, SIOP-PNET-4, EU-20244, UKCCSG-CNS-2003-05
Study First Received:	February 5, 2003
Last Updated:	August 23, 2008
ClinicalTrials.gov Identifier:	NCT00053872
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

untreated childhood medulloblastoma

Study placed in the following topic categories:

Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Cisplatin
Neoplasms, Germ Cell and Embryonal
Lomustine
Medulloblastoma

Vincristine
Neuroepithelioma
Glioma
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Neoplasms, Nerve Tissue
Nervous System Diseases
Mitosis Modulators
Antimitotic Agents

Pharmacologic Actions
Neoplasms
Neoplasms by Site
Therapeutic Uses
Tubulin Modulators
Neoplasms, Neuroepithelial
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on January 16, 2009