Clinical trial NCT00003573: Etoposide Plus Radiation Therapy Followed by Combination Chemotherapy in Treating Children With Newly Diagnosed Advanced Medulloblastoma
Official title: A Phase I/II Feasibility Study of Oral Etoposide Given Concurrently With Radiotherapy Followed With Dose Intensive Adjuvant Chemotherapy for Children With Newly Diagnosed High Stage Medulloblastoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Brain Tumors
Central Nervous System Tumors
Keywords: untreated childhood medulloblastoma
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-02-20
Enrollment: 53
Sex: ALL
Minimum age (years): 3
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining radiation therapy with chemotherapy may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of etoposide plus radiation therapy followed by combination chemotherapy in treating children with newly diagnosed advanced medulloblastoma.

Detailed description: OBJECTIVES:

* Assess the response rate and toxicity of oral etoposide and radiotherapy in children with newly diagnosed high stage medulloblastoma.
* Compare the response rate and toxicity of these patients to historical control patients registered on POG #9031.
* Estimate the 2-year event-free survival and overall survival of these patients.
* Evaluate the toxicity of dose intensive chemotherapy with oral etoposide, cisplatin, cyclophosphamide, and vincristine following craniospinal irradiation in these patients.

OUTLINE: Patients begin treatment within 1 month of surgery. Patients receive 6 weeks of radiotherapy to the head and spine, with boosts to the posterior fossa and to sites of metastasis. Patients also receive 2 courses of oral etoposide once daily for 3 weeks concurrent with and immediately following radiotherapy (weeks 1-3 and 5-7).

Patients then receive adjuvant chemotherapy consisting of cisplatin IV once every 4 weeks for 3 courses beginning on week 11, oral etoposide daily for 21 days every 4 weeks for 3 courses (weeks 11, 15, and 19), cyclophosphamide IV on days 1 and 2 with filgrastim (G-CSF) SQ daily for at least 10 days every 4 weeks for 8 courses (weeks 23-51), and vincristine IV on days 1, 8, and 15 every 4 weeks for 8 courses (weeks 23-51).

Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year, and annually thereafter.

PROJECTED ACCRUAL: A total of 48 patients will be accrued for this study within about 2 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically diagnosed advanced (high grade) childhood medulloblastoma
* Residual disease of at least 1.5 cm2 in size on MRI or CT scan OR
* Evidence of CNS or extraneural metastases

PATIENT CHARACTERISTICS:

Age:

* 3 to 21

Performance status:

* Not specified

Life expectancy:

* Not specified

Hematopoietic:

* Absolute neutrophil count at least 1,500/mm\^3
* Platelet count at least 100,000/mm\^3

Hepatic:

* SGPT less than 5 times normal
* Bilirubin less than 1.5 mg/dL

Renal:

* Creatinine less than 1.7 mg/dL OR
* Creatinine clearance greater than 70 mL/min

Other:

* Not pregnant or nursing
* 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:

* Not specified

Primary outcomes:
measure: Assess the efficacy of oral etoposide at 50 mg/m2/day given concurrently with radiotherapy followed with dose intensive adjuvant chemotherapy in children with newly diagnosed high stage medulloblastoma
timeFrame: End of course 1 (week 10)
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Comprehensive Cancer Center
state: Alabama
city: Mobile
country: United States
facility: MBCCOP - Gulf Coast
state: Alabama
city: Tucson
country: United States
facility: Arizona Cancer Center
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: La Jolla
country: United States
facility: University of California San Diego Cancer Center
state: California
city: Palo Alto
country: United States
facility: Lucile Packard Children's Hospital at Stanford
state: California
city: Sacramento
country: United States
facility: Sutter Cancer Center
state: California
city: Sacramento
country: United States
facility: University of California Davis Medical Center
state: California
city: San Diego
country: United States
facility: Kaiser Permanente-Southern California Permanente Medical Group
state: California
city: San Diego
country: United States
facility: Children's Hospital and Health Center
state: California
city: San Diego
country: United States
facility: Naval Medical Center - San Diego
state: California
city: Santa Clara
country: United States
facility: Kaiser Permanente Medical Center - Santa Clara
state: California
city: New Haven
country: United States
facility: Yale Comprehensive Cancer Center
state: Connecticut
city: Washington
country: United States
facility: Walter Reed Army Medical Center
state: District of Columbia
city: Gainesville
country: United States
facility: Shands Hospital and Clinics, University of Florida
state: Florida
city: Jacksonville
country: United States
facility: Nemours Children's Clinic
state: Florida
city: Miami
country: United States
facility: Sylvester Cancer Center, University of Miami
state: Florida
city: Miami
country: United States
facility: Miami Children's Hospital
state: Florida
city: Orlando
country: United States
facility: Walt Disney Memorial Cancer Institute
state: Florida
city: Tampa
country: United States
facility: CCOP - Florida Pediatric
state: Florida
city: West Palm Beach
country: United States
facility: St. Mary's Hospital
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital - Atlanta
state: Georgia
city: Honolulu
country: United States
facility: Cancer Research Center of Hawaii
state: Hawaii
city: Honolulu
country: United States
facility: Tripler Army Medical Center
state: Hawaii
city: Chicago
country: United States
facility: Rush-Presbyterian-St. Luke's Medical Center
state: Illinois
city: Chicago
country: United States
facility: Children's Memorial Hospital, Chicago
state: Illinois
city: Oak Lawn
country: United States
facility: Hope Children's Hospital
state: Illinois
city: Peoria
country: United States
facility: Saint Jude Midwest Affiliate
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: Wichita
country: United States
facility: Via Christi Regional Medical Center
state: Kansas
city: New Orleans
country: United States
facility: MBCCOP - LSU Health Sciences Center
state: Louisiana
city: New Orleans
country: United States
facility: Tulane University School of Medicine
state: Louisiana
city: New Orleans
country: United States
facility: CCOP - Ochsner
state: Louisiana
city: Bangor
country: United States
facility: Eastern Maine Medical Center
state: Maine
city: Portland
country: United States
facility: Maine Children's Cancer Program
state: Maine
city: Baltimore
country: United States
facility: Marlene & Stewart Greenebaum Cancer Center, University of Maryland
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Oncology Center
state: Maryland
city: Boston
country: United States
facility: Boston Floating Hospital Infants and Children
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Memorial Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Children's Hospital of Michigan
state: Michigan
city: Detroit
country: United States
facility: St. John's Hospital and Medical Center
state: Michigan
city: Flint
country: United States
facility: Hurley Medical Center
state: Michigan
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Keesler AFB
country: United States
facility: Keesler Medical Center - Keesler AFB
state: Mississippi
city: Columbia
country: United States
facility: University of Missouri-Columbia Hospital and Clinics
state: Missouri
city: Saint Louis
country: United States
facility: Cardinal Glennon Children's Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Lebanon
country: United States
facility: Norris Cotton Cancer Center
state: New Hampshire
city: Hackensack
country: United States
facility: CCOP - Northern New Jersey
state: New Jersey
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico School of Medicine
state: New Mexico
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New Hyde Park
country: United States
facility: Schneider Children's Hospital
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Rochester
country: United States
facility: University of Rochester Cancer Center
state: New York
city: Stony Brook
country: United States
facility: State University of New York Health Sciences Center - Stony Brook
state: New York
city: Syracuse
country: United States
facility: State University of New York - Upstate Medical University
state: New York
city: Asheville
country: United States
facility: Mission Saint Joseph's Health System
state: North Carolina
city: Charlotte
country: United States
facility: Carolinas Medical Center
state: North Carolina
city: Charlotte
country: United States
facility: Presbyterian Healthcare
state: North Carolina
city: Durham
country: United States
facility: Duke Comprehensive Cancer Center
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University School of Medicine
state: North Carolina
city: Winston-Salem
country: United States
facility: Comprehensive Cancer Center at Wake Forest University
state: North Carolina
city: Oklahoma City
country: United States
facility: Oklahoma Memorial Hospital
state: Oklahoma
city: Tulsa
country: United States
facility: Natalie Warren Bryant Cancer Center
state: Oklahoma
city: Portland
country: United States
facility: CCOP - Columbia River Program
state: Oregon
city: Portland
country: United States
facility: Legacy Emanuel Hospital and Health Center
state: Oregon
city: Philadelphia
country: United States
facility: St. Christopher's Hospital for Children
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Greenville
country: United States
facility: Children's Hospital of Greenville Hospital System
state: South Carolina
city: Johnson City
country: United States
facility: James H. Quillen College of Medicine
state: Tennessee
city: Memphis
country: United States
facility: Saint Jude Children's Research Hospital
state: Tennessee
city: Dallas
country: United States
facility: Medical City Dallas Hospital
state: Texas
city: Dallas
country: United States
facility: Simmons Cancer Center - Dallas
state: Texas
city: Fort Worth
country: United States
facility: Cook Children's Medical Center - Fort Worth
state: Texas
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Lackland Air Force Base
country: United States
facility: San Antonio Military Pediatric Cancer and Blood Disorders Center
state: Texas
city: San Antonio
country: United States
facility: MBCCOP - South Texas Pediatric
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Temple
country: United States
facility: Scott and White Clinic
state: Texas
city: Burlington
country: United States
facility: Vermont Cancer Center
state: Vermont
city: Falls Church
country: United States
facility: Inova Fairfax Hospital
state: Virginia
city: Portsmouth
country: United States
facility: Naval Medical Center, Portsmouth
state: Virginia
city: Richmond
country: United States
facility: Massey Cancer Center
state: Virginia
city: Roanoke
country: United States
facility: Carilion Roanoke Community Hospital
state: Virginia
city: Tacoma
country: United States
facility: Madigan Army Medical Center
state: Washington
city: Charleston
country: United States
facility: West Virginia University Medical School-Charleston
state: West Virginia
city: Morgantown
country: United States
facility: West Virginia University Hospitals
state: West Virginia
city: Green Bay
country: United States
facility: St. Vincent Hospital
state: Wisconsin
city: Milwaukee
country: United States
facility: Midwest Children's Cancer Center
state: Wisconsin
city: Calgary
country: Canada
facility: Alberta Children's Hospital
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Hamilton
country: Canada
facility: Children's Hospital
state: Ontario
city: Ottawa
country: Canada
facility: Children's Hospital of Eastern Ontario
state: Ontario
city: Toronto
country: Canada
facility: Hospital for Sick Children
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Center - Montreal Children's Hospital
state: Quebec
city: Montreal
country: Canada
facility: Hopital Sainte Justine
state: Quebec
city: Sainte Foy
country: Canada
facility: Centre Hospitalier de L'Universite Laval
state: Quebec
city: Groningen
country: Netherlands
facility: Academisch Ziekenhuis Groningen
city: Santurce
country: Puerto Rico
facility: San Jorge Childrens Hospital
city: Bern
country: Switzerland
facility: Swiss Pediatric Oncology Group Bern
city: Geneva
country: Switzerland
facility: Clinique de Pediatrie
Study officials:
affiliation: Hopital Sainte Justine
name: Albert Moghrabi, MD
role: STUDY_CHAIR
References:
citation: Tarbell NJ, Friedman H, Polkinghorn WR, Yock T, Zhou T, Chen Z, Burger P, Barnes P, Kun L. High-risk medulloblastoma: a pediatric oncology group randomized trial of chemotherapy before or after radiation therapy (POG 9031). J Clin Oncol. 2013 Aug 10;31(23):2936-41. doi: 10.1200/JCO.2012.43.9984. Epub 2013 Jul 15.