Combination Chemotherapy in Treating Children With Newly Diagnosed Malignant Germ Cell Tumors
NCT ID: NCT00066482
Last Updated: 2013-10-17
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
NA
19 participants
INTERVENTIONAL
2004-07-31
Brief Summary
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PURPOSE: Phase I trial to study the effect on the body of combining cyclophosphamide with cisplatin, etoposide, and bleomycin in treating children who have newly diagnosed malignant germ cell tumors that are not in the brain and gonads.
Detailed Description
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* Determine the maximum tolerated dose and toxicity profile of cyclophosphamide in combination with bleomycin, etoposide, and cisplatin in pediatric patients with newly diagnosed high-risk extracranial, extragonadal malignant germ cell tumors.
* Determine the response rate in patients treated with this regimen.
OUTLINE: This is a pilot, multicenter, dose-escalation study of cyclophosphamide.
* Induction therapy: Patients receive bleomycin IV over 10-20 minutes on day 1, etoposide IV over 1 hour and cisplatin IV over 4 hours on days 1-5, and cyclophosphamide IV over 1 hour on day 1. Patients also receive filgrastim (G-CSF) subcutaneously once daily beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 6 patients receive escalating doses of cyclophosphamide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.
Patients are evaluated after 4 courses of therapy. Patients with partial response or stable disease undergo second-look surgery, receive 2 more courses of induction therapy, and are then re-evaluated. Patients who do not achieve complete response (CR) after a total of 6 courses may undergo a third surgery. Patients who still have tumor that cannot be removed are removed from study therapy. Patients who achieve a CR at anytime are followed.
Patients are followed monthly for 1 year, every 6 months for 1 year, and then annually for 3 years.
PROJECTED ACCRUAL: A total of 6-18 patients will be accrued for this study within 1.3 years.
Conditions
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Keywords
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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combination chemotherapy
Induction therapy: bleomycin sulfate IV over 10-20 minutes on day 1, etoposide IV over 1 hour and cisplatin IV over 4 hours on days 1-5, and cyclophosphamide IV over 1 hour on day 1. MESNA \& Filgrastim (G-CSF) subcutaneously once daily beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. 6 patients receive escalating doses of cyclophosphamide until the maximum tolerated dose (MTD) is determined.
Evaluated after 4 courses of therapy. Partial response or stable disease undergo second-look conventional surgery \& receive 2 more courses of induction therapy then re-evaluated. Those who do not achieve complete response (CR) after a total of 6 courses may undergo a third conventional surgery. Tumor that cannot be removed are removed from study therapy. Achievement of a CR at anytime are followed monthly for 1 year, every 6 months for 1 year, and then annually for 3 years.
bleomycin sulfate
Given IV over 10 minutes. Children ≥ 12 months: 15 units/m2/dose Children \< 12 months: 0.5 units/kg/dose Day 1 (Week 1, 4, 7, 10)
filgrastim
Given SQ once daily 5 micrograms/kg/dose Starting on Day 6 (Week 1, 4, 7, 10) Daily until ANC \> 5,000/uL
cisplatin
Children ≥ 12 months: Given IV over one hour Dose: 20 mg/m2/dose Days 1-5 (Week 1,4,7,10) Children \< 12 months: Given IV over 4 hours, 0.67 mg/kg/dose Days 1-5 (Week 1,4,7,10)
cyclophosphamide
Given IV over 1 hour. Children ≥ 12 months: Level 1: 1.2 g/m2/dose Level 2: 1.8 g/m2/dose Level 3: 2.4 g/m2/dose Children \< 12 months: Level 1: 40 mg/kg/dose Level 2: 60 mg/kg/dose Level 3: 80 mg/kg/dose Day 1 (Week 1, 4, 7, 10)
etoposide
Given IV over 1 hour. Children ≥ 12 months: 100 mg/m2/dose Children \< 12 months: 3.3 mg/kg/dose Day 1-5 (Week 1, 4, 7, 10)
conventional surgery
Stage III/IV extragonadal tumors: biopsy followed by a definitive surgical excision after maximal chemotherapy effect, likely after 4 cycles of therapy
MESNA
Given IV or oral. The total daily MESNA dose is equal to at least 80% of the daily CPM dose. The oral dose of MESNA is 2x the IV dose. Day 1 (Week 1,4,7,10) To be given with CPM.
Interventions
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bleomycin sulfate
Given IV over 10 minutes. Children ≥ 12 months: 15 units/m2/dose Children \< 12 months: 0.5 units/kg/dose Day 1 (Week 1, 4, 7, 10)
filgrastim
Given SQ once daily 5 micrograms/kg/dose Starting on Day 6 (Week 1, 4, 7, 10) Daily until ANC \> 5,000/uL
cisplatin
Children ≥ 12 months: Given IV over one hour Dose: 20 mg/m2/dose Days 1-5 (Week 1,4,7,10) Children \< 12 months: Given IV over 4 hours, 0.67 mg/kg/dose Days 1-5 (Week 1,4,7,10)
cyclophosphamide
Given IV over 1 hour. Children ≥ 12 months: Level 1: 1.2 g/m2/dose Level 2: 1.8 g/m2/dose Level 3: 2.4 g/m2/dose Children \< 12 months: Level 1: 40 mg/kg/dose Level 2: 60 mg/kg/dose Level 3: 80 mg/kg/dose Day 1 (Week 1, 4, 7, 10)
etoposide
Given IV over 1 hour. Children ≥ 12 months: 100 mg/m2/dose Children \< 12 months: 3.3 mg/kg/dose Day 1-5 (Week 1, 4, 7, 10)
conventional surgery
Stage III/IV extragonadal tumors: biopsy followed by a definitive surgical excision after maximal chemotherapy effect, likely after 4 cycles of therapy
MESNA
Given IV or oral. The total daily MESNA dose is equal to at least 80% of the daily CPM dose. The oral dose of MESNA is 2x the IV dose. Day 1 (Week 1,4,7,10) To be given with CPM.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Histologically confirmed newly diagnosed extracranial germ cell tumors, including 1 of the following types:
* Yolk sac carcinoma (endodermal sinus tumor)
* Embryonal carcinoma
* Choriocarcinoma
* Teratoma with mixed malignant elements (malignant teratoma)
* High-risk disease, defined as stage III or IV extragonadal germ cell tumors
* Must be enrolled on study within 21 days of diagnostic surgical procedure
PATIENT CHARACTERISTICS:
Age
* 21 and under (at original diagnosis)
Performance status
* ECOG 0-2
* Karnofsky 50-100% (in patients over 16 years of age)
* Lansky 50-100% (in patients 16 years of age and under)
Life expectancy
* At least 2 months
Hematopoietic
* Absolute neutrophil count at least 1,000/mm\^3
* Platelet count at least 100,000/mm\^3 (transfusion independent)
* Hemoglobin at least 10.0 g/dL (transfusion allowed)
Hepatic
* Not specified
Renal
* Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min OR
* Creatinine based on age as follows:
* No greater than 0.8 mg/dL (5 years and under)
* No greater than 1.0 mg/dL (6-10 years)
* No greater than 1.2 mg/dL (11-15 years)
* No greater than 1.5 mg/dL (over 15 years)
Pulmonary
* FEV\_1/FVC greater than 60% OR
* Children who are uncooperative must meet all of the following criteria:
* No dyspnea at rest
* No exercise intolerance
* Pulse oximetry greater than 94%
Other
* Not pregnant or nursing
* Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy
* Not specified
Chemotherapy
* No prior chemotherapy
Endocrine therapy
* Not specified
Radiotherapy
* No prior radiotherapy
Surgery
* See Disease Characteristics
21 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
Children's Oncology Group
NETWORK
Responsible Party
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Principal Investigators
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Marcio A. Malogolowkin, MD
Role: STUDY_CHAIR
Children's Hospital Los Angeles
Locations
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Comprehensive Cancer Center at University of Alabama at Birmingham
Birmingham, Alabama, United States
Phoenix Children's Hospital
Phoenix, Arizona, United States
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
Southern California Permanente Medical Group
Downey, California, United States
Loma Linda University Cancer Institute at Loma Linda University Medical Center
Loma Linda, California, United States
Children's Hospital Los Angeles
Los Angeles, California, United States
Children's Hospital Central California
Madera, California, United States
Children's Hospital of Orange County
Orange, California, United States
Kaiser Permanente Medical Center - Oakland
Sacramento, California, United States
Children's Hospital and Health Center - San Diego
San Diego, California, United States
Stanford Cancer Center at Stanford University Medical Center
Stanford, California, United States
Children's Hospital Cancer Center
Denver, Colorado, United States
Alfred I. duPont Hospital for Children
Wilmington, Delaware, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
Lee Cancer Care of Lee Memorial Health System
Fort Myers, Florida, United States
University of Florida Shands Cancer Center
Gainesville, Florida, United States
Nemours Children's Clinic
Jacksonville, Florida, United States
University of Miami Sylvester Comprehensive Cancer Center
Miami, Florida, United States
Miami Children's Hospital
Miami, Florida, United States
Baptist-South Miami Regional Cancer Program
Miami, Florida, United States
Sacred Heart Cancer Center at Sacred Heart Hospital
Pensacola, Florida, United States
All Children's Hospital
St. Petersburg, Florida, United States
St. Joseph's Cancer Institute at St. Joseph's Hospital
Tampa, Florida, United States
Kaplan Cancer Center at St. Mary's Medical Center
West Palm Beach, Florida, United States
Emory University Hospital - Atlanta
Atlanta, Georgia, United States
Cancer Research Center of Hawaii
Honolulu, Hawaii, United States
Children's Memorial Hospital - Chicago
Chicago, Illinois, United States
Saint Jude Midwest Affiliate
Peoria, Illinois, United States
Southern Illinois University School of Medicine
Springfield, Illinois, United States
St. Vincent Indianapolis Hospital
Indianapolis, Indiana, United States
Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
Kansas City, Kansas, United States
Markey Cancer Center at University of Kentucky Chandler Medical Center
Lexington, Kentucky, United States
CancerCare of Maine at Eastern Maine Medial Center
Bangor, Maine, United States
Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
Baltimore, Maryland, United States
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States
C.S. Mott Children's Hospital at University of Michigan
Ann Arbor, Michigan, United States
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States
Hurley Medical Center
Flint, Michigan, United States
Spectrum Health Cancer Care - Butterworth Campus
Grand Rapids, Michigan, United States
Van Elslander Cancer Center at St. John Hospital and Medical Center
Grosse Pointe Woods, Michigan, United States
Breslin Cancer Center at Ingham Regional Medical Center
Lansing, Michigan, United States
Children's Hospital of Minnesota - Minneapolis
Minneapolis, Minnesota, United States
Fairview University Medical Center - University Campus
Minneapolis, Minnesota, United States
Mayo Clinic Cancer Center
Rochester, Minnesota, United States
University of Mississippi Medical Center
Jackson, Mississippi, United States
Ellis Fischel Cancer Center at University of Missouri - Columbia
Columbia, Missouri, United States
Children's Mercy Hospital
Kansas City, Missouri, United States
Siteman Cancer Center at Barnes-Jewish Hospital
St Louis, Missouri, United States
Hackensack University Medical Center Cancer Center
Hackensack, New Jersey, United States
St. Barnabas Medical Center
Livingston, New Jersey, United States
James P. Wilmot Cancer Center at University of Rochester Medical Center
Rochester, New York, United States
SUNY Upstate Medical University Hospital
Syracuse, New York, United States
Albert Einstein Cancer Center at Albert Einstein College of Medicine
The Bronx, New York, United States
New York Medical College
Valhalla, New York, 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
Duke Comprehensive Cancer Center
Durham, North Carolina, United States
Children's Hospital Medical Center of Akron
Akron, Ohio, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
Children's Medical Center - Dayton
Dayton, Ohio, United States
Tod Children's Hospital - Forum Health
Youngstown, Ohio, United States
Oklahoma University Medical Center
Oklahoma City, Oklahoma, United States
Penn State Cancer Institute at Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
St. Christopher's Hospital for Children
Philadelphia, Pennsylvania, United States
Hollings Cancer Center at Medical University of South Carolina
Charleston, South Carolina, United States
Greenville Hospital System Cancer Center
Greenville, South Carolina, United States
East Tennessee Children's Hospital
Knoxville, Tennessee, United States
St. Jude Children's Research Hospital
Memphis, Tennessee, United States
Texas Tech University Health Sciences Center School of Medicine
Amarillo, Texas, United States
Children's Hospital of Austin
Austin, Texas, United States
Driscoll Children's Hospital
Corpus Christi, Texas, United States
Medical City Dallas Hospital
Dallas, Texas, United States
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
Dallas, Texas, United States
Cook Children's Medical Center - Fort Worth
Fort Worth, Texas, United States
Baylor University Medical Center - Houston
Houston, Texas, United States
M.D. Anderson Cancer Center at University of Texas
Houston, Texas, United States
Covenant Children's Hospital
Lubbock, Texas, United States
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States
Methodist Children's Hospital of South Texas
San Antonio, Texas, United States
Primary Children's Medical Center
Salt Lake City, Utah, United States
INOVA Fairfax Hospital
Fairfax, Virginia, United States
Carilion Cancer Center of Western Virginia
Roanoke, Virginia, United States
West Virginia University - Robert C. Byrd Health Sciences Center - Charleston Division
Charleston, West Virginia, United States
St. Vincent Hospital Regional Cancer Center
Green Bay, Wisconsin, United States
University of Wisconsin Comprehensive Cancer Center
Madison, Wisconsin, United States
Marshfield Clinic - Marshfield Center
Marshfield, Wisconsin, United States
Midwest Children's Cancer Center
Milwaukee, Wisconsin, United States
Princess Margaret Hospital for Children
Perth, Western Australia, Australia
Children's & Women's Hospital of British Columbia
Vancouver, British Columbia, Canada
Janeway Children's Health and Rehabilitation Centre
St. John's, Newfoundland and Labrador, Canada
McMaster Children's Hospital at Hamilton Health Sciences
Hamilton, Ontario, Canada
Hospital for Sick Children
Toronto, Ontario, Canada
Montreal Children's Hospital at McGill University Health Center
Montreal, Quebec, Canada
Hopital Sainte Justine
Montreal, Quebec, Canada
Centre Hospitalier Universitaire de Quebec
Ste-Foy, Quebec, Canada
Allan Blair Cancer Centre at Pasqua Hospital
Regina, Saskatchewan, Canada
San Jorge Children's Hospital
Santurce, , Puerto Rico
Countries
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Other Identifiers
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CDR0000316244
Identifier Type: OTHER
Identifier Source: secondary_id
AGCT01P1
Identifier Type: -
Identifier Source: org_study_id