Comparison of Radiation Therapy Regimens in Combination With Chemotherapy in Treating Young Patients With Newly Diagnosed Standard-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:	NCT00085735

Purpose

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy, such as vincristine, cisplatin, lomustine, and cyclophosphamide, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving radiation therapy with chemotherapy after surgery may kill any remaining tumor cells. It is not yet known whether standard-dose radiation therapy combined with chemotherapy after surgery is more effective than reduced-dose craniospinal (head and spine) radiation therapy plus either posterior fossa (back of the brain) boost or tumor bed (site of the tumor) boost radiation therapy combined with chemotherapy in treating medulloblastoma.

PURPOSE: This randomized phase III trial is studying standard-dose radiation therapy to see how well it works compared to reduced-dose craniospinal radiation therapy AND posterior fossa boost radiation therapy to see how well it works compared to tumor bed boost radiation therapy when given together with chemotherapy in treating young patients who have undergone surgery for newly diagnosed standard-risk medulloblastoma.

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

MedlinePlus related topics: Cancer

Drug Information available for: Cyclophosphamide Vincristine sulfate Vincristine Cisplatin Lomustine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
Official Title:	A Study Evaluating Limited Target Volume Boost Irradiation and Reduced Dose Craniospinal (18.00 Gy) and Chemotherapy in Children With Newly Diagnosed Standard Risk Medulloblastoma: A Phase III Double Randomized Trial

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

Primary Outcome Measures:

Time to event as measured by the time to disease progression, disease recurrence, death from any cause, or occurrence of a second malignant neoplasm at 3 years [ Designated as safety issue: No ]

Secondary Outcome Measures:

Time to recurrence, progression, or death due to cancer at 3 years [ Designated as safety issue: No ]
Time to death at 3 years [ Designated as safety issue: No ]
Local Posterior Fossa (LPF) Failure as determined by tumor recurrence or progression within the tumor bed at 3 years [ Designated as safety issue: No ]
Non-local Posterior Fossa (NLPF) Failure as determined by recurrence outside CTVboost but within CTVPF at 3 years [ Designated as safety issue: No ]
Non-Posterior Fossa (NPF) Failure as determine by recurrence within the neuroaxis but outside of CTVPF at 3 years [ Designated as safety issue: No ]
Post-treatment neurocognitive function as measured by Neuropsychometric battery at 3 years [ Designated as safety issue: No ]
Post-treatment hearing loss as measure by Audiogram or brainstem auditory evoked response (BAER) at 3 years [ Designated as safety issue: No ]
Post-treatment endocrine function (e.g., growth, sexual maturation, and need for hormone replacement) by laboratory assesment, clinical history, and exam at 3 years [ Designated as safety issue: No ]
Quality of Life as measured by Pediatric Quality of Life Inventory (PedsQL), Behavior Assessment System for Children (BASC), Behavior Rating Inventory of Executive Function (BRIEF), and Adaptive Behavior Assessment System (ABAS) at 3 years [ Designated as safety issue: No ]

Estimated Enrollment:	455
Study Start Date:	April 2004
Estimated Primary Completion Date:	March 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I: Experimental Patients undergo reduced-dose craniospinal radiotherapy with boost.	Procedure: radiation therapy Given on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47 (weeks 0-6) at different doses.
Arm II: Active Comparator Patients undergo standard-dose craniospinal radiotherapy with boost.	Procedure: radiation therapy Given on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47 (weeks 0-6) at different doses.
Arm III: Active Comparator Patients will undergo radiotherapy boost to the entire posterior fossa.	Procedure: radiation therapy Given on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47 (weeks 0-6) at different doses.
Arm IV: Experimental Patients will undergo radiotherapy boost to the tumor bed only.	Procedure: radiation therapy Given on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47 (weeks 0-6) at different doses.
Regimen A (courses 1, 2, 4, 5, 7, and 8): Experimental Patients receive oral lomustine and cisplatin IV over 6 hours on day 1 and vincristine IV on days 1, 8, and 15 of weeks 11, 17, 27, 33, 43, and 49.	Drug: cisplatin Given IV Drug: lomustine Given orally Drug: vincristine sulfate Given IV
Regimen B (courses 3, 6, and 9): Experimental Patients receive cyclophosphamide IV over 1 hour on days 1 and 2 and vincristine IV on days 1 and 8 of weeks 23, 39, and 55.	Drug: cyclophosphamide Given IV Drug: vincristine sulfate Given IV

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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 located in the posterior fossa
- Standard-risk disease
Minimal volume, non-disseminated disease, defined by the following:
- Residual tumor ≤ 1.5 cm^2 confirmed by MRI with contrast imaging within 21 days after surgery
- No metastatic disease in the head, spine, or cerebrospinal fluid (CSF) confirmed by both of the following:
  - Enhanced MRI of the spine within 5 days before surgery OR within 28 days after surgery
  - Negative cytological examination of CSF after surgery, but before study enrollment
Brain stem involvement allowed

PATIENT CHARACTERISTICS:

Age

3 to 21 at diagnosis

Performance status

Karnofsky 50-100% (> 16 years of age) OR
Lansky 30-100% (≤ 16 years of age)

Life expectancy

Not specified

Hematopoietic

Absolute neutrophil count > 1,500/mm^3
Platelet count > 100,000/mm^3 (transfusion independent)
Hemoglobin > 10 g/dL (transfusions allowed)

Hepatic

Bilirubin < 1.5 times upper limit of normal (ULN)
AST or ALT < 1.5 times ULN

Renal

Creatinine clearance OR radioisotope glomerular filtration rate ≥ 70 mL/min

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception

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: NCT00085735

Show 174 Study Locations

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:

Jeff M. Michalski, MD

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

More Information

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

Study ID Numbers:	CDR0000365506, COG-ACNS0331
Study First Received:	June 14, 2004
Last Updated:	January 13, 2009
ClinicalTrials.gov Identifier:	NCT00085735
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

untreated childhood medulloblastoma

Study placed in the following topic categories:

Neuroectodermal Tumors, Primitive
Lomustine
Vincristine
Central Nervous System Neoplasms
Cyclophosphamide
Neuroectodermal Tumors
Cisplatin

Neoplasms, Germ Cell and Embryonal
Medulloblastoma
Neuroepithelioma
Glioma
Nervous System Neoplasms
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Mitosis Modulators
Neoplasms, Nerve Tissue
Nervous System Diseases
Physiological Effects of Drugs
Antimitotic Agents
Immunosuppressive Agents
Pharmacologic Actions

Neoplasms
Neoplasms by Site
Therapeutic Uses
Tubulin Modulators
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Neoplasms, Neuroepithelial
Antirheumatic Agents
Antineoplastic Agents, Phytogenic
Alkylating Agents

ClinicalTrials.gov processed this record on January 16, 2009