RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctors to give higher doses of chemotherapy drugs and kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy plus peripheral stem cell transplantation in treating infants with malignant brain or spinal cord tumors.

Condition	Treatment or Intervention	Phase
childhood brain tumor childhood rhabdoid tumor of the central nervous system childhood rhabdomyosarcoma childhood spinal cord tumors Neuroblastoma	Drug: carboplatin  Drug: cisplatin  Drug: cyclophosphamide  Drug: etoposide  Drug: filgrastim  Drug: thiotepa  Drug: vincristine  Procedure: biological response modifier therapy  Procedure: bone marrow ablation with stem cell support  Procedure: chemotherapy  Procedure: colony-stimulating factor therapy  Procedure: conventional surgery  Procedure: cytokine therapy  Procedure: peripheral blood stem cell transplantation  Procedure: surgery	Phase I

Further Study Details: 

OBJECTIVES:

• Determine the maximum tolerated dose of thiotepa in infants with malignant brain or spinal cord tumors receiving intensive chemotherapy.
• Determine the feasibility and toxicity of intensive chemotherapy with peripheral blood stem cell (PBSC) rescue in these patients.
• Assess the feasibility of harvesting PBSCs in these patients.
• Determine the complete response rate and overall event-free survival rate in patients treated with this regimen.

OUTLINE: This is a pilot, multicenter study.

Patients undergo surgery for diagnosis and maximal tumor resection.

Within 6 weeks of surgery or when stable, patients begin induction chemotherapy comprising cisplatin IV over 6 hours on day 0; vincristine IV on days 0, 7, and 14; cyclophosphamide IV over 1 hour on days 1-2; and etoposide IV over 1 hour on days 0-2. Twenty four hours after the last cyclophosphamide dose, patients receive filgrastim (G-CSF) subcutaneously (SC) and undergo peripheral blood stem cell harvest 2 days later. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Within 6 weeks after induction chemotherapy, patients receive consolidation chemotherapy comprising carboplatin IV over 2 hours on days 0-1 followed immediately by escalating doses of thiotepa IV over 2 hours. Patients then undergo peripheral blood stem cell transplantation 48 hours after the last thiotepa dose. Patients receive G-CSF SC daily on days 3 to 21. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Patients experiencing dose-limiting toxicity due to thiotepa are removed from the study.

Patients are followed at 4 weeks, every 3 months for 1 year, every 6 months for 3 years, and then annually for 3 years or until relapse.

PROJECTED ACCRUAL: A total of 83 patients will be accrued for this study within 1 year.

Ages Eligible for Study:  up to  2 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically proven malignant brain or spinal cord tumor, including the following:
• Primitive neuroectodermal tumor
• Ganglioneuroblastoma
• Medulloblastoma neuroblastoma
• Desmoplastic medulloblastoma
• Medulloepithelioma
• Ependymoma neuroepithelioma
• Anaplastic ependymoma germ cell tumor
• Astrocytoma germinoma
• Anaplastic astrocytoma
• Embryonal carcinoma
• Glioblastoma endodermal sinus tumor
• Gliosarcoma malignant teratoma
• Choroid plexus carcinoma
• Mixed germ cell tumor
• Cerebellar sarcoma
• Pineoblastoma
• Atypical teratoid/rhabdoid tumor
• Choriocarcinoma
• Teratoma (malignant or with malignant transformations)
• Diffusely involved brain stem tumors allowed if there is evidence of brain stem glioma by CT scan or MRI

PATIENT CHARACTERISTICS: Age:

• 6 months to less than 3 years

Performance Status:

• Not specified

Life Expectancy:

• More than 8 weeks

Hematopoietic:

• Absolute neutrophil count greater than 1,000/mm^3
• Platelet count greater than 100,000/mm^3

Hepatic:

• Bilirubin less than 2.0 mg/dL

Renal:

• Glomerular filtration rate or creatinine clearance greater than 70 mL/min

PRIOR CONCURRENT THERAPY: Biologic therapy:

• No prior biologic therapy

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• Prior corticosteroids allowed

Radiotherapy:

• No prior radiotherapy

Surgery:

• No more than 6 weeks since prior surgery
• Recovered from prior surgery (stable)

Arizona
      Phoenix Children's Hospital, Phoenix,  Arizona,  85016,  United States
California
      Cedars-Sinai Comprehensive Cancer Center at Cedars-Sinai Medical Center, Los Angeles,  California,  90048,  United States
      Chao Family Comprehensive Cancer Center at University of California Irvine Cancer Center, Orange,  California,  92868,  United States
      Children's Hospital and Research Center at Oakland, Oakland,  California,  94609-1809,  United States
      Children's Hospital Central California, Madera,  California,  93638-8762,  United States
      Children's Hospital Los Angeles, Los Angeles,  California,  90027-0700,  United States
      Children's Hospital of Orange County, Orange,  California,  92868,  United States
      City of Hope Comprehensive Cancer Center, Duarte,  California,  91010-3000,  United States
      David Grant Medical Center, Travis Air Force Base,  California,  94535,  United States
      Jonathan Jaques Children's Cancer Center at Miller Children's Hospital, Long Beach,  California,  90801-1428,  United States
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-1781,  United States
      Kaiser Permanente Medical Center - Sacramento, Sacramento,  California,  95825,  United States
      Loma Linda University Cancer Institute at Loma Linda University Medical Center, Loma Linda,  California,  92354,  United States
      Santa Barbara Cottage Hospital, Santa Barbara,  California,  93102,  United States
      Southern California Permanente Medical Group, Downey,  California,  90242,  United States
      UCSF Comprehensive Cancer Center, San Francisco,  California,  94143,  United States
Colorado
      Children's Hospital of Denver, Denver,  Colorado,  80218-1088,  United States
      Presbyterian - St. Luke's Medical Center, Denver,  Colorado,  80218,  United States
Connecticut
      University of Connecticut Comprehensive Cancer Center at University of Connecticut Health Center, Farmington,  Connecticut,  06360-7106,  United States
Delaware
      Alfred I. duPont Hospital for Children, Wilmington,  Delaware,  19899,  United States
District of Columbia
      Children's National Medical Center, Washington,  District of Columbia,  20010-2970,  United States
      Lombardi Cancer Center at Georgetown University Medical Center, Washington,  District of Columbia,  20007,  United States
Georgia
      Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center, Savannah,  Georgia,  31403-3089,  United States
      MBCCOP-Medical College of Georgia Cancer Center, Augusta,  Georgia,  30912-4000,  United States
      Medical Center of Central Georgia, Macon,  Georgia,  31201,  United States
Idaho
      Mountain States Tumor Institute - Boise, Boise,  Idaho,  83712,  United States
Illinois
      Cardinal Bernardin Cancer Center at Loyola University Medical Center, Maywood,  Illinois,  60153,  United States
      Lutheran General Cancer Care Center, Park Ridge,  Illinois,  60068-1174,  United States
      Southern Illinois University School of Medicine, Springfield,  Illinois,  62794-9658,  United States
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60601,  United States
      University of Illinois Medical Center, Chicago,  Illinois,  60612,  United States
Indiana
      Riley Children Cancer Center at Riley Hospital for Children, Indianapolis,  Indiana,  46202-5225,  United States
      St. Vincent Hospitals and Health Care Centers, Indianapolis,  Indiana,  46260,  United States
Iowa
      Blank Children's Hospital, Des Moines,  Iowa,  50308,  United States
      Holden Comprehensive Cancer Center at University of Iowa, Iowa City,  Iowa,  52242-1009,  United States
Kentucky
      Kosair Children's Hospital, Louisville,  Kentucky,  40202-3830,  United States
      Markey Cancer Center at University of Kentucky Chandler Medical Center, Lexington,  Kentucky,  40536-0284,  United States
Maryland
      Alvin and Lois Lapidus Cancer Institute at Sinai Hospital, Baltimore,  Maryland,  21225,  United States
Massachusetts
      Baystate Regional Cancer Program at Baystate Medical Center, Springfield,  Massachusetts,  01107,  United States
Michigan
      CCOP - Kalamazoo, Kalamazoo,  Michigan,  49007-5364,  United States
      Josephine Ford Cancer Center at Henry Ford Health System, Detroit,  Michigan,  48202,  United States
      Spectrum Health and DeVos Children's Hospital, Grand Rapids,  Michigan,  49503,  United States
      University of Michigan Comprehensive Cancer Center, Ann Arbor,  Michigan,  48109-0914,  United States
      William Beaumont Hospital - Royal Oak, Royal Oak,  Michigan,  48073-6769,  United States
Minnesota
      CCOP - Duluth, Duluth,  Minnesota,  55805,  United States
      Children's Hospitals and Clinics - Minneapolis, Minneapolis,  Minnesota,  55404,  United States
      Children's Hospitals and Clinics - Minnesota, Saint Paul,  Minnesota,  55102,  United States
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States
      University of Minnesota Cancer Center, Minneapolis,  Minnesota,  55455,  United States
Missouri
      Children's Mercy Hospital, Kansas City,  Missouri,  64108,  United States
Nebraska
      Children's Hospital of Omaha, Omaha,  Nebraska,  68114,  United States
      UNMC Eppley Cancer Center at the University of Nebraska Medical Center, Omaha,  Nebraska,  68198-2168,  United States
Nevada
      Sunrise Hospital and Medical Center, Las Vegas,  Nevada,  89119,  United States
New Jersey
      Cancer Institute of New Jersey at Robert Wood Johnson University Hospital, New Brunswick,  New Jersey,  08903,  United States
      Newark Beth Israel Medical Center, Newark,  New Jersey,  07112-2094,  United States
      St. Barnabas Medical Center, Livingston,  New Jersey,  07039,  United States
      St. Joseph's Hospital and Medical Center, Paterson,  New Jersey,  07503,  United States
      Valerie Fund Children's Center at Atlantic Health, Summit,  New Jersey,  07901,  United States
New York
      Albert Einstein Clinical Cancer Center, Bronx,  New York,  10461,  United States
      Brookdale University Hospital and Medical Center, Brooklyn,  New York,  11212,  United States
      Brooklyn Hospital Center, Brooklyn,  New York,  11201-5493,  United States
      Comprehensive Cancer Center at Maimonides Medical Center, Brooklyn,  New York,  11219,  United States
      Herbert Irving Comprehensive Cancer Center at Columbia University, New York,  New York,  10032,  United States
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States
      New York Medical College, Valhalla,  New York,  10595,  United States
      New York Weill Cornell Cancer Center at Cornell University, New York,  New York,  10021,  United States
      NYU School of Medicine's Kaplan Comprehensive Cancer Center, New York,  New York,  10016,  United States
      Schneider Children's Hospital, New Hyde Park,  New York,  11042,  United States
      SUNY Downstate Medical Center, Brooklyn,  New York,  11203,  United States
North Carolina
      Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill, Chapel Hill,  North Carolina,  27599-7295,  United States
North Dakota
      Dakota Cancer Institute at Innovis Health - Dakota Clinic, Fargo,  North Dakota,  58103-4940,  United States
      Meritcare Roger Maris Cancer Center, Fargo,  North Dakota,  58122,  United States
Ohio
      Children's Medical Center - Dayton, Dayton,  Ohio,  45404,  United States
      Cincinnati Children's Hospital Medical Center, Cincinnati,  Ohio,  45229-3039,  United States
      Cleveland Clinic Taussig Cancer Center, Cleveland,  Ohio,  44195,  United States
      Columbus Children's Hospital, Columbus,  Ohio,  43205-2696,  United States
      Forum Health-Tod Childrens Hospital, Youngstown,  Ohio,  44501,  United States
      Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University, Cleveland,  Ohio,  44106-5065,  United States
      St. Vincent Mercy Medical Center, Toledo,  Ohio,  43608,  United States
      Toledo Children's Hospital, Toledo,  Ohio,  43601,  United States
Oregon
      Doernbecher Children's Hospital at Oregon Health & Science University, Portland,  Oregon,  97239-3098,  United States
Pennsylvania
      Children's Hospital of Philadelphia, Philadelphia,  Pennsylvania,  19104,  United States
      Children's Hospital of Pittsburgh, Pittsburgh,  Pennsylvania,  15213-2583,  United States
      Geisinger Medical Center, Danville,  Pennsylvania,  17822-1320,  United States
      Penn State Cancer Institute at Milton S. Hershey Medical Center, Hershey,  Pennsylvania,  17033,  United States
South Carolina
      Palmetto Health South Carolina Cancer Center, Columbia,  South Carolina,  29203,  United States
South Dakota
      Avera Cancer Institute, Sioux Falls,  South Dakota,  57105-1080,  United States
      Sioux Valley Hospital at University of South Dakota Medical Center, Sioux Falls,  South Dakota,  57117-5039,  United States
Tennessee
      East Tennessee Children's Hospital, Knoxville,  Tennessee,  37901,  United States
      Vanderbilt Children's Hospital, Nashville,  Tennessee,  37232-6310,  United States
Texas
      Children's Hospital of Austin, Austin,  Texas,  78701,  United States
      Covenant Children's Hospital, Lubbock,  Texas,  79410,  United States
      MBCCOP - South Texas Pediatrics, San Antonio,  Texas,  78229-3900,  United States
      Methodist Cancer Center at Methodist Specialty and Transplant Hospital, San Antonio,  Texas,  78229-3902,  United States
      Texas Tech University Health Sciences Center School of Medicine, Amarillo,  Texas,  79106,  United States
      University of Texas - MD Anderson Cancer Center, Houston,  Texas,  77030-4009,  United States
Utah
      Primary Children's Medical Center, Salt Lake City,  Utah,  84113,  United States
Virginia
      Children's Hospital of the King's Daughters, Norfolk,  Virginia,  23507,  United States
Washington
      Children's Hospital and Regional Medical Center - Seattle, Seattle,  Washington,  98105,  United States
      Deaconess Medical Center, Spokane,  Washington,  99210-0248,  United States
      Group Health Eastside Hospital, Redmond,  Washington,  98052,  United States
      Mary Bridge Children's Hospital and Health Center, Tacoma,  Washington,  98415-0299,  United States
West Virginia
      Cabell Huntington Hospital, Huntington,  West Virginia,  25701,  United States
Wisconsin
      Bellin Memorial Hospital, Green Bay,  Wisconsin,  54301,  United States
      Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center, La Crosse,  Wisconsin,  54601,  United States
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792-6164,  United States
Australia, New South Wales
      Sydney Children's Hospital, Randwick,  New South Wales,  2031,  Australia
Australia, Western Australia
      Princess Margaret Hospital for Children, Perth,  Western Australia,  6006,  Australia
Canada, British Columbia
      British Columbia Children's Hospital, Vancouver,  British Columbia,  V6H 3V4,  Canada
Canada, Manitoba
      CancerCare Manitoba, Winnipeg,  Manitoba,  R3E 0V9,  Canada
Canada, Newfoundland and Labrador
      Janeway Children's Health and Rehabilitation Centre, St. John's,  Newfoundland and Labrador,  A1B 3V6,  Canada
Canada, Ontario
      Children's Hospital of Western Ontario, London,  Ontario,  N6C 2V5,  Canada
Canada, Saskatchewan
      Allan Blair Cancer Centre at Pasqua Hospital, Regina,  Saskatchewan,  S4T 7T1,  Canada
New Zealand
      Starship Children's Health, Auckland,  New Zealand

Study chairs or principal investigators

Bruce H. Cohen, MD,  Study Chair,  Cleveland Clinic Cancer Center   

Study ID Numbers:  CDR0000065924; COG-99703; CCG-99703; NCT00003141
Record last reviewed:  January 2005
Last Updated:  January 10, 2005
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003141
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08