Combination Chemotherapy in Treating Children With Progressive Brain Tumors

Brain Tumors Clinical Trial

Official title:

Chemotherapy for Progressive Low Grade Astrocytoma in Children Less Than Ten Years Old

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002944
• Other study ID #: A9952
• Secondary ID: CCG-A9952POG-A99
• Status: Completed
• Phase: Phase 3
• First received: November 1, 1999
• Last updated: September 6, 2013
• Start date: April 1997
• Est. completion date: April 2012

Study information

• Verified date: September 2013
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• 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. Combining more than one drug may kill more tumor cells.

PURPOSE: This randomized phase III trial is studying two different combination chemotherapy regimens and comparing how well they work in treating children with low-grade astrocytomas or other residual tumors of the brain.

Description:

OBJECTIVES:

• Compare the event free survival as a result of treatment with carboplatin and vincristine versus thioguanine, procarbazine, lomustine, and vincristine in children with progressive brain tumors.

• Estimate tumor response rates to each regimen of chemotherapy in these patients.

• Determine toxic effects and quality of life of children treated with each regimen of chemotherapy.

• Investigate biological and clinical factors which may predict tumor response and early progression (tumor size, location, pathologic subtype, cytogenetics, and proliferative index by MIB-1 (Ki67)) in these patients.

• Investigate factors contributing to neuropsychological and endocrine status of children with brain tumors treated without irradiation.

OUTLINE: This is a randomized study. Patients are stratified according to site of disease, status at entry, and pathology. Patients are randomized to one of two treatment arms. Patients with neurofibromatosis are nonrandomly assigned to arm II.

• Arm I: Patients receive induction with carboplatin and vincristine for 10 weeks followed by 2 weeks of rest. Induction is followed by 8 courses of maintenance beginning on day 84 of induction or upon hematopoietic recovery. Each course consists of 4 weekly doses of carboplatin and 3 weekly doses of vincristine (given concurrently with the first 3 weeks of carboplatin), followed by 2 weeks of rest.

• Arm II: Patients receive oral thioguanine, procarbazine, and lomustine on days 0-4, followed by vincristine IV on days 14 and 28. Treatment continues every 6 weeks for a maximum of 8 courses.

PROJECTED ACCRUAL: A total of 280-340 patients will be accrued over 4 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 428
• Est. completion date: April 2012
• Est. primary completion date: February 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 9 Years

Eligibility

DISEASE CHARACTERISTICS:

• Pathologically confirmed low grade residual astrocytomas or other eligible residual tumors of the brain interpreted as low grade (WHO grades I and II) such as the following:

• Glial Tumors

• Astrocytic tumors

• Low grade astrocytoma (variants: fibrillary, protoplasmic, gemistocytic)

• Pilocytic astrocytoma

• Pleomorphic xanthoastrocytomas

• Subependymal giant cell astrocytoma

• Infantile desmoplastic astrocytoma

• Low grade oligodendroglial tumors

• Low grade oligodendroglioma

• Low grade mixed gliomas

• Oligo-astrocytoma

• Neuronal Tumors

• Ganglioglioma (excluding tumors with anaplastic astrocytic components)

• Infantile desmoplastic ganglioglioma

• Chiasmatic-hypothalamic tumor without histologic confirmation

• All of the following diagnostic tests (radiological or clinical evidence of progression, surgery, or confirmatory MRI) must be carried out within 6 weeks of enrollment into this study

• Progressive disease following surgical excision based on clear radiological or clinical evidence of progression, or an incomplete excision (less than 95% or greater than 1.5 cm2) with necessity to begin treatment because of a risk of neurologic impairment with progression

• Chiasmatic lesions that have contiguous extensions of tumor into other regions of the visual pathways demonstrated on contrast MRI will be eligible for study without histopathological confirmation

• Patients with neurofibromatosis who have radiographic diagnosis of chiasmatic-hypothalamic tumor are eligible for the study, without requiring a biopsy confirmation of tumor histology, but not unless tumor progression is documented radiographically

• No intrinsic brain stem tumors of the pons or isolated optic nerve tumors without definitive involvement of the optic chiasm

PATIENT CHARACTERISTICS:

Age:

• Under 10

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count greater than 1,000/mm^3 (arm II)

• Platelet count greater than 100,000/mm^3 (arm II)

Hepatic:

• Not specified

Renal:

• Creatinine less than 1.5 times upper limit of normal for age OR

• Creatinine clearance or radioisotope GFR greater than 70 mL/min or equivalent GFR as determined by the institutional normal range

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy for the tumor

Endocrine therapy:

• Prior corticosteroid therapy allowed

Radiotherapy:

• No prior radiotherapy for the tumor

Surgery:

• See Disease characteristics

Other:

• Prior diuretic therapy allowed

Study Design

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• carboplatin
Given IV
• lomustine
Given IV
• procarbazine hydrochloride
Given PO
• thioguanine
Given PO
• vincristine sulfate
Given PO and IV

Locations

Country	Name	City	State
Australia	Royal Children's Hospital	Brisbane	Queensland
Australia	John Hunter Hospital	Newcastle	New South Wales
Australia	Princess Margaret Hospital for Children	Perth	Western Australia
Australia	Prince of Wales Private Hospital	Randwick	New South Wales
Australia	Children's Hospital at Westmead	Westmead	New South Wales
Canada	Alberta Children's Hospital	Calgary	Alberta
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	IWK Health Centre	Halifax	Nova Scotia
Canada	McMaster Children's Hospital at Hamilton Health Sciences	Hamilton	Ontario
Canada	Cancer Centre of Southeastern Ontario at Kingston General Hospital	Kingston	Ontario
Canada	Children's Hospital of Western Ontario	London	Ontario
Canada	Hopital Sainte Justine	Montreal	Quebec
Canada	Montreal Children's Hospital at McGill University Health Center	Montreal	Quebec
Canada	Children's Hospital of Eastern Ontario	Ottawa	Ontario
Canada	Centre Hospitalier Universitaire de Quebec	Quebec
Canada	Allan Blair Cancer Centre at Pasqua Hospital	Regina	Saskatchewan
Canada	Saskatoon Cancer Centre at the University of Saskatchewan	Saskatoon	Saskatchewan
Canada	Janeway Children's Health and Rehabilitation Centre	St. John's	Newfoundland and Labrador
Canada	Hospital for Sick Children	Toronto	Ontario
Canada	Children's & Women's Hospital of British Columbia	Vancouver	British Columbia
Canada	CancerCare Manitoba	Winnipeg	Manitoba
Netherlands	University Medical Center Groningen	Groningen
New Zealand	Starship Children's Health	Auckland
Switzerland	Swiss Pediatric Oncology Group Bern	Bern
Switzerland	Swiss Pediatric Oncology Group Geneva	Geneva
United States	Akron Children's Hospital	Akron	Ohio
United States	Albany Medical Center Hospital	Albany	New York
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Tulane Cancer Center Office of Clinical Research	Alexandria	Louisiana
United States	Texas Tech University Health Sciences Center School of Medicine - Amarillo	Amarillo	Texas
United States	C.S. Mott Children's Hospital at University of Michigan Medical Center	Ann Arbor	Michigan
United States	AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus	Atlanta	Georgia
United States	AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Scottish Rite Campus	Atlanta	Georgia
United States	MBCCOP - Medical College of Georgia Cancer Center	Augusta	Georgia
United States	Children's Hospital Center for Cancer and Blood Disorders	Aurora	Colorado
United States	Dell Children's Medical Center of Central Texas	Austin	Texas
United States	Alvin and Lois Lapidus Cancer Institute at Sinai Hospital	Baltimore	Maryland
United States	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland
United States	CancerCare of Maine at Eastern Maine Medical Center	Bangor	Maine
United States	Mountain States Tumor Institute at St. Luke's Regional Medical Center	Boise	Idaho
United States	Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Albert Einstein Cancer Center at Albert Einstein College of Medicine	Bronx	New York
United States	Maimonides Cancer Center at Maimonides Medical Center	Brooklyn	New York
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Fletcher Allen Health Care - University Health Center Campus	Burlington	Vermont
United States	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina
United States	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina
United States	West Virginia University Health Sciences Center - Charleston	Charleston	West Virginia
United States	Blumenthal Cancer Center at Carolinas Medical Center	Charlotte	North Carolina
United States	Presbyterian Cancer Center at Presbyterian Hospital	Charlotte	North Carolina
United States	Children's Memorial Hospital - Chicago	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	University of Illinois Cancer Center	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	Rainbow Babies and Children's Hospital	Cleveland	Ohio
United States	Ellis Fischel Cancer Center at University of Missouri - Columbia	Columbia	Missouri
United States	Palmetto Health South Carolina Cancer Center	Columbia	South Carolina
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Driscoll Children's Hospital	Corpus Christi	Texas
United States	Geisinger Cancer Institute at Geisinger Health	Danville	Pennsylvania
United States	Dayton Children's - Dayton	Dayton	Ohio
United States	Blank Children's Hospital	Des Moines	Iowa
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Southern California Permanente Medical Group	Downey	California
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	CCOP - Duluth	Duluth	Minnesota
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	CCOP - MeritCare Hospital	Fargo	North Dakota
United States	Dakota Cancer Institute at Dakota Clinic - South University	Fargo	North Dakota
United States	Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center	Farmington	Connecticut
United States	Hurley Medical Center	Flint	Michigan
United States	Broward General Medical Center Cancer Center	Fort Lauderdale	Florida
United States	Lee Cancer Care of Lee Memorial Health System	Fort Myers	Florida
United States	Cook Children's Medical Center - Fort Worth	Fort Worth	Texas
United States	University of Florida Shands Cancer Center	Gainesville	Florida
United States	University of Texas Medical Branch	Galveston	Texas
United States	Butterworth Hospital at Spectrum Health	Grand Rapids	Michigan
United States	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan
United States	Hackensack University Medical Center Cancer Center	Hackensack	New Jersey
United States	Penn State Children's Hospital	Hershey	Pennsylvania
United States	Memorial Cancer Institute at Memorial Regional Hospital	Hollywood	Florida
United States	Cancer Research Center of Hawaii	Honolulu	Hawaii
United States	M. D. Anderson Cancer Center at University of Texas	Houston	Texas
United States	Edwards Comprehensive Cancer Center at Cabell Huntington Hospital	Huntington	West Virginia
United States	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	St. Vincent Indianapolis Hospital	Indianapolis	Indiana
United States	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa
United States	University of Mississippi Cancer Clinic	Jackson	Mississippi
United States	Nemours Children's Clinic	Jacksonville	Florida
United States	CCOP - Kalamazoo	Kalamazoo	Michigan
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas
United States	Keesler Air Force Base Medical Center	Keesler AFB	Mississippi
United States	East Tennessee Children's Hospital	Knoxville	Tennessee
United States	Gundersen Lutheran Center for Cancer and Blood	La Crosse	Wisconsin
United States	Wilford Hall Medical Center	Lackland AFB	Texas
United States	Breslin Cancer Center at Ingham Regional Medical Center	Lansing	Michigan
United States	CCOP - Nevada Cancer Research Foundation	Las Vegas	Nevada
United States	Lucille P. Markey Cancer Center at University of Kentucky	Lexington	Kentucky
United States	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	St. Barnabas Medical Center Cancer Center	Livingston	New Jersey
United States	Loma Linda University Cancer Institute at Loma Linda University Medical Center	Loma Linda	California
United States	Jonathan Jaques Children's Cancer Center at Miller Children's Hospital	Long Beach	California
United States	Childrens Hospital Los Angeles	Los Angeles	California
United States	Jonsson Comprehensive Cancer Center at UCLA	Los Angeles	California
United States	Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center	Los Angeles	California
United States	Kosair Children's Hospital	Louisville	Kentucky
United States	Covenant Children's Hospital	Lubbock	Texas
United States	Medical Center of Central Georgia	Macon	Georgia
United States	Children's Hospital Central California	Madera	California
United States	Don Monti Comprehensive Cancer Center at North Shore University Hospital	Manhasset	New York
United States	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin
United States	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois
United States	Baptist-South Miami Regional Cancer Program	Miami	Florida
United States	Miami Children's Hospital	Miami	Florida
United States	Children's Hospitals and Clinics of Minnesota - Minneapolis	Minneapolis	Minnesota
United States	Masonic Cancer Center at University of Minnesota	Minneapolis	Minnesota
United States	University of South Alabama Mitchell Cancer Institute	Mobile	Alabama
United States	Mary Babb Randolph Cancer Center at West Virginia University Hospitals	Morgantown	West Virginia
United States	Overlook Hospital	Morristown	New Jersey
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School	New Brunswick	New Jersey
United States	Saint Peter's University Hospital	New Brunswick	New Jersey
United States	Yale Cancer Center	New Haven	Connecticut
United States	Schneider Children's Hospital	New Hyde Park	New York
United States	Children's Hospital of New Orleans	New Orleans	Louisiana
United States	Ochsner Cancer Institute at Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Beth Israel Medical Center - Petrie Division	New York	New York
United States	Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center	New York	New York
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	NYU Cancer Institute at New York University Medical Center	New York	New York
United States	St. Luke's - Roosevelt Hospital Center - St.Luke's Division	New York	New York
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	Children's Hospital of The King's Daughters	Norfolk	Virginia
United States	Keyser Family Cancer Center at Advocate Hope Children's Hospital	Oak Lawn	Illinois
United States	Children's Hospital and Research Center Oakland	Oakland	California
United States	Oklahoma University Cancer Institute	Oklahoma City	Oklahoma
United States	Children's Hospital	Omaha	Nebraska
United States	Children's Hospital of Orange County	Orange	California
United States	Florida Hospital Cancer Institute at Florida Hospital Orlando	Orlando	Florida
United States	M.D. Anderson Cancer Center at Orlando	Orlando	Florida
United States	Nemours Children's Clinic - Orlando	Orlando	Florida
United States	Lucile Packard Children's Hospital at Stanford University Medical Center	Palo Alto	California
United States	Advocate Lutheran General Cancer Care Center	Park Ridge	Illinois
United States	St. Joseph's Hospital and Medical Center	Paterson	New Jersey
United States	Sacred Heart Cancer Center at Sacred Heart Hospital	Pensacola	Florida
United States	Saint Jude Midwest Affiliate	Peoria	Illinois
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	St. Christopher's Hospital for Children	Philadelphia	Pennsylvania
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	Knight Cancer Institute at Oregon Health and Science University	Portland	Oregon
United States	Legacy Emanuel Hospital and Health Center and Children's Hospital	Portland	Oregon
United States	Naval Medical Center - Portsmouth	Portsmouth	Virginia
United States	Virginia Commonwealth University Massey Cancer Center	Richmond	Virginia
United States	Carilion Medical Center for Children at Roanoke Community Hospital	Roanoke	Virginia
United States	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Swedish-American Regional Cancer Center	Rockford	Illinois
United States	William Beaumont Hospital - Royal Oak Campus	Royal Oak	Michigan
United States	Kaiser Permanente Medical Center - Oakland	Sacramento	California
United States	Sutter Cancer Center	Sacramento	California
United States	University of California Davis Cancer Center	Sacramento	California
United States	All Children's Hospital	Saint Petersburg	Florida
United States	Primary Children's Medical Center	Salt Lake City	Utah
United States	Methodist Children's Hospital of South Texas	San Antonio	Texas
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Rady Children's Hospital - San Diego	San Diego	California
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California
United States	Santa Barbara Cottage Children's Hospital	Santa Barbara	California
United States	Kaiser Permanente Medical Center - Santa Clara Kiely Campus	Santa Clara	California
United States	Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center	Savannah	Georgia
United States	Maine Children's Cancer Program at Barbara Bush Children's Hospital	Scarborough	Maine
United States	Children's Hospital and Regional Medical Center - Seattle	Seattle	Washington
United States	Group Health Central Hospital	Seattle	Washington
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota
United States	Deaconess Medical Center	Spokane	Washington
United States	Providence Cancer Center at Sacred Heart Medical Center	Spokane	Washington
United States	Baystate Regional Cancer Program at D'Amour Center for Cancer Care	Springfield	Massachusetts
United States	Simmons Cooper Cancer Institute	Springfield	Illinois
United States	Cardinal Glennon Children's Hospital	St. Louis	Missouri
United States	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis	St. Louis	Missouri
United States	Children's Hospitals and Clinics of Minnesota - St. Paul	St. Paul	Minnesota
United States	Stony Brook University Cancer Center	Stony Brook	New York
United States	SUNY Upstate Medical University Hospital	Syracuse	New York
United States	Madigan Army Medical Center - Tacoma	Tacoma	Washington
United States	Mary Bridge Children's Hospital and Health Center - Tacoma	Tacoma	Washington
United States	St. Joseph's Cancer Institute at St. Joseph's Hospital	Tampa	Florida
United States	CCOP - Scott and White Hospital	Temple	Texas
United States	Medical University of Ohio Cancer Center	Toledo	Ohio
United States	Toledo Hospital	Toledo	Ohio
United States	New York Medical College	Valhalla	New York
United States	Children's National Medical Center	Washington	District of Columbia
United States	Lombardi Comprehensive Cancer Center at Georgetown University Medical Center	Washington	District of Columbia
United States	Kaplan Cancer Center at St. Mary's Medical Center	West Palm Beach	Florida
United States	CCOP - Wichita	Wichita	Kansas
United States	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas
United States	Wesley Medical Center	Wichita	Kansas
United States	Alfred I. duPont Hospital for Children	Wilmington	Delaware
United States	Tod Children's Hospital	Youngstown	Ohio

Sponsors (2)

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

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Netherlands,  New Zealand,  Switzerland, 

References & Publications (1)

Ater JL, Zhou T, Holmes E, Mazewski CM, Booth TN, Freyer DR, Lazarus KH, Packer RJ, Prados M, Sposto R, Vezina G, Wisoff JH, Pollack IF. Randomized study of two chemotherapy regimens for treatment of low-grade glioma in young children: a report from the C — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event Free Survival	Compare the event-free survival as a result of treatment with either CV or TPCV	Time from study entry until disease progression, death without progression of disease, occurrence of a second malignant neoplasm or last follow-up, whichever comes first, assessed up to 5 years	No
Secondary	Survival	Defined as the time to death from any cause.	5 years	No