Etoposide Plus Radiation Therapy Followed by Combination Chemotherapy in Treating Children With Newly Diagnosed Advanced Medulloblastoma

Brain Tumors Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003573
• Other study ID #: 9631
• Secondary ID: POG-9631CDR00000
• Status: Completed
• Phase: Phase 2
• First received: November 1, 1999
• Last updated: July 24, 2014
• Start date: November 1998
• Est. completion date: March 2008

Study information

• Verified date: July 2014
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: March 2008
• Est. primary completion date: October 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 3 Years to 21 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain Tumors
• Central Nervous System Neoplasms
• Central Nervous System Tumors
• Medulloblastoma
• Nervous System Neoplasms

Intervention

Biological:
• filgrastim

Drug:
• cisplatin

• cyclophosphamide

• etoposide

• vincristine sulfate

Radiation:
• radiation therapy

Locations

Country	Name	City	State
Canada	Alberta Children's Hospital	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Children's Hospital	Hamilton	Ontario
Canada	Hopital Sainte Justine	Montreal	Quebec
Canada	McGill University Health Center - Montreal Children's Hospital	Montreal	Quebec
Canada	Children's Hospital of Eastern Ontario	Ottawa	Ontario
Canada	Centre Hospitalier de L'Universite Laval	Sainte Foy	Quebec
Canada	Hospital for Sick Children	Toronto	Ontario
Netherlands	Academisch Ziekenhuis Groningen	Groningen
Puerto Rico	San Jorge Childrens Hospital	Santurce
Switzerland	Swiss Pediatric Oncology Group Bern	Bern
Switzerland	Clinique de Pediatrie	Geneva
United States	University of New Mexico School of Medicine	Albuquerque	New Mexico
United States	Mission Saint Joseph's Health System	Asheville	North Carolina
United States	Emory University Hospital - Atlanta	Atlanta	Georgia
United States	Johns Hopkins Oncology Center	Baltimore	Maryland
United States	Marlene & Stewart Greenebaum Cancer Center, University of Maryland	Baltimore	Maryland
United States	Eastern Maine Medical Center	Bangor	Maine
United States	University of Alabama at Birmingham Comprehensive Cancer Center	Birmingham	Alabama
United States	Boston Floating Hospital Infants and Children	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Vermont Cancer Center	Burlington	Vermont
United States	Medical University of South Carolina	Charleston	South Carolina
United States	West Virginia University Medical School-Charleston	Charleston	West Virginia
United States	Carolinas Medical Center	Charlotte	North Carolina
United States	Presbyterian Healthcare	Charlotte	North Carolina
United States	Children's Memorial Hospital, Chicago	Chicago	Illinois
United States	Rush-Presbyterian-St. Luke's Medical Center	Chicago	Illinois
United States	University of Missouri-Columbia Hospital and Clinics	Columbia	Missouri
United States	Medical City Dallas Hospital	Dallas	Texas
United States	Simmons Cancer Center - Dallas	Dallas	Texas
United States	Children's Hospital of Michigan	Detroit	Michigan
United States	St. John's Hospital and Medical Center	Detroit	Michigan
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	Hurley Medical Center	Flint	Michigan
United States	Cook Children's Medical Center - Fort Worth	Fort Worth	Texas
United States	Shands Hospital and Clinics, University of Florida	Gainesville	Florida
United States	University of Texas Medical Branch	Galveston	Texas
United States	St. Vincent Hospital	Green Bay	Wisconsin
United States	Children's Hospital of Greenville Hospital System	Greenville	South Carolina
United States	East Carolina University School of Medicine	Greenville	North Carolina
United States	CCOP - Northern New Jersey	Hackensack	New Jersey
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Cancer Research Center of Hawaii	Honolulu	Hawaii
United States	Tripler Army Medical Center	Honolulu	Hawaii
United States	Baylor College of Medicine	Houston	Texas
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Nemours Children's Clinic	Jacksonville	Florida
United States	James H. Quillen College of Medicine	Johnson City	Tennessee
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Keesler Medical Center - Keesler AFB	Keesler AFB	Mississippi
United States	University of California San Diego Cancer Center	La Jolla	California
United States	San Antonio Military Pediatric Cancer and Blood Disorders Center	Lackland Air Force Base	Texas
United States	Norris Cotton Cancer Center	Lebanon	New Hampshire
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Saint Jude Children's Research Hospital	Memphis	Tennessee
United States	Miami Children's Hospital	Miami	Florida
United States	Sylvester Cancer Center, University of Miami	Miami	Florida
United States	Midwest Children's Cancer Center	Milwaukee	Wisconsin
United States	MBCCOP - Gulf Coast	Mobile	Alabama
United States	West Virginia University Hospitals	Morgantown	West Virginia
United States	Yale Comprehensive Cancer Center	New Haven	Connecticut
United States	Schneider Children's Hospital	New Hyde Park	New York
United States	CCOP - Ochsner	New Orleans	Louisiana
United States	MBCCOP - LSU Health Sciences Center	New Orleans	Louisiana
United States	Tulane University School of Medicine	New Orleans	Louisiana
United States	Mount Sinai School of Medicine	New York	New York
United States	Hope Children's Hospital	Oak Lawn	Illinois
United States	Oklahoma Memorial Hospital	Oklahoma City	Oklahoma
United States	Walt Disney Memorial Cancer Institute	Orlando	Florida
United States	Lucile Packard Children's Hospital at Stanford	Palo Alto	California
United States	Saint Jude Midwest Affiliate	Peoria	Illinois
United States	St. Christopher's Hospital for Children	Philadelphia	Pennsylvania
United States	CCOP - Columbia River Program	Portland	Oregon
United States	Legacy Emanuel Hospital and Health Center	Portland	Oregon
United States	Maine Children's Cancer Program	Portland	Maine
United States	Naval Medical Center, Portsmouth	Portsmouth	Virginia
United States	Massey Cancer Center	Richmond	Virginia
United States	Carilion Roanoke Community Hospital	Roanoke	Virginia
United States	University of Rochester Cancer Center	Rochester	New York
United States	Sutter Cancer Center	Sacramento	California
United States	University of California Davis Medical Center	Sacramento	California
United States	Cardinal Glennon Children's Hospital	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	MBCCOP - South Texas Pediatric	San Antonio	Texas
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Children's Hospital and Health Center	San Diego	California
United States	Kaiser Permanente-Southern California Permanente Medical Group	San Diego	California
United States	Naval Medical Center - San Diego	San Diego	California
United States	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California
United States	State University of New York Health Sciences Center - Stony Brook	Stony Brook	New York
United States	State University of New York - Upstate Medical University	Syracuse	New York
United States	Madigan Army Medical Center	Tacoma	Washington
United States	CCOP - Florida Pediatric	Tampa	Florida
United States	Scott and White Clinic	Temple	Texas
United States	Arizona Cancer Center	Tucson	Arizona
United States	Natalie Warren Bryant Cancer Center	Tulsa	Oklahoma
United States	Walter Reed Army Medical Center	Washington	District of Columbia
United States	St. Mary's Hospital	West Palm Beach	Florida
United States	CCOP - Wichita	Wichita	Kansas
United States	Via Christi Regional Medical Center	Wichita	Kansas
United States	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina
United States	University of Massachusetts Memorial Medical Center	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Children's Oncology Group	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada,  Netherlands,  Puerto Rico,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	It is possible that unacceptably high levels of toxicity may arise. For this reason, there is a 3-stage stopping rule designed to allow the Study Coordinator to stop this study early if it appears that the true proportion of eligible patients who suffer unacceptable levels of toxicity exceeds 10%.	End of course 1 (week 10)	Yes