Combination Chemotherapy in Treating Children With Newly Diagnosed Malignant Germ Cell Tumors
- Conditions
- Childhood Germ Cell TumorExtragonadal Germ Cell Tumor
- Interventions
- Biological: bleomycin sulfateBiological: filgrastimProcedure: conventional surgeryBiological: MESNA
- Registration Number
- NCT00066482
- Lead Sponsor
- Children's Oncology Group
- Brief 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: 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
OBJECTIVES:
* 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 19
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description combination chemotherapy bleomycin sulfate 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. combination chemotherapy filgrastim 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. combination chemotherapy conventional surgery 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. combination chemotherapy MESNA 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. combination chemotherapy cisplatin 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. combination chemotherapy cyclophosphamide 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. combination chemotherapy etoposide 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.
- Primary Outcome Measures
Name Time Method Feasibility of adding cyclophosphamide to a PEB backbone 2 years
- Secondary Outcome Measures
Name Time Method Maximum tolerated dose 21 days Maximum tolerated dose (MTD) and toxicity profile of cyclophosphamide combined with cisplatin, etoposide, bleomycin (C-PEB) in previously untreated children with high-risk malignant germ cell tumors (MGCT).
Estimate the response rate Length of study To estimate the response rate in this group of patients to a regimen of cyclophosphamide combined with cisplatin, etoposide, bleomycin (C-PEB).
Trial Locations
- Locations (98)
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Medical City Dallas Hospital
🇺🇸Dallas, Texas, United States
Children's Memorial Hospital - Chicago
🇺🇸Chicago, Illinois, United States
University of Miami Sylvester Comprehensive Cancer Center
🇺🇸Miami, Florida, United States
Baptist-South Miami Regional Cancer Program
🇺🇸Miami, Florida, United States
St. Vincent Indianapolis Hospital
🇺🇸Indianapolis, Indiana, United States
Children's Hospital of Orange County
🇺🇸Orange, California, United States
Lee Cancer Care of Lee Memorial Health System
🇺🇸Fort Myers, Florida, United States
Breslin Cancer Center at Ingham Regional Medical Center
🇺🇸Lansing, Michigan, United States
Tod Children's Hospital - Forum Health
🇺🇸Youngstown, Ohio, United States
Children's Hospital Central California
🇺🇸Madera, California, United States
Stanford Cancer Center at Stanford University Medical Center
🇺🇸Stanford, California, United States
Kaplan Cancer Center at St. Mary's Medical Center
🇺🇸West Palm Beach, Florida, United States
Alfred I. duPont Hospital for Children
🇺🇸Wilmington, Delaware, United States
Siteman Cancer Center at Barnes-Jewish Hospital
🇺🇸St. Louis, Missouri, United States
St. Christopher's Hospital for Children
🇺🇸Philadelphia, Pennsylvania, United States
James P. Wilmot Cancer Center at University of Rochester Medical Center
🇺🇸Rochester, New York, United States
All Children's Hospital
🇺🇸St. Petersburg, Florida, United States
Spectrum Health Cancer Care - Butterworth Campus
🇺🇸Grand Rapids, Michigan, United States
Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
🇺🇸Baltimore, Maryland, United States
Blumenthal Cancer Center at Carolinas Medical Center
🇺🇸Charlotte, North Carolina, United States
Children's & Women's Hospital of British Columbia
🇨🇦Vancouver, British Columbia, Canada
Hopital Sainte Justine
🇨🇦Montreal, Quebec, Canada
Allan Blair Cancer Centre at Pasqua Hospital
🇨🇦Regina, Saskatchewan, Canada
Ellis Fischel Cancer Center at University of Missouri - Columbia
🇺🇸Columbia, Missouri, United States
Emory University Hospital - Atlanta
🇺🇸Atlanta, Georgia, United States
Children's Medical Center - Dayton
🇺🇸Dayton, Ohio, United States
Greenville Hospital System Cancer Center
🇺🇸Greenville, South Carolina, United States
Hurley Medical Center
🇺🇸Flint, Michigan, United States
Van Elslander Cancer Center at St. John Hospital and Medical Center
🇺🇸Grosse Pointe Woods, Michigan, United States
Marshfield Clinic - Marshfield Center
🇺🇸Marshfield, Wisconsin, United States
East Tennessee Children's Hospital
🇺🇸Knoxville, Tennessee, United States
Centre Hospitalier Universitaire de Quebec
🇨🇦Ste-Foy, Quebec, 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
INOVA Fairfax Hospital
🇺🇸Fairfax, Virginia, United States
Hospital for Sick Children
🇨🇦Toronto, Ontario, Canada
Children's Hospital and Health Center - San Diego
🇺🇸San Diego, California, 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
Children's Hospital of Minnesota - Minneapolis
🇺🇸Minneapolis, Minnesota, United States
Duke Comprehensive Cancer Center
🇺🇸Durham, North Carolina, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Princess Margaret Hospital for Children
🇦🇺Perth, Western Australia, Australia
Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States
New York Medical College
🇺🇸Valhalla, New York, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
Primary Children's Medical Center
🇺🇸Salt Lake City, Utah, United States
Barbara Ann Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Oklahoma University Medical Center
🇺🇸Oklahoma City, Oklahoma, United States
Comprehensive Cancer Center at University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Children's Hospital Cancer Center
🇺🇸Denver, Colorado, United States
St. Joseph's Cancer Institute at St. Joseph's Hospital
🇺🇸Tampa, Florida, United States
Mayo Clinic Cancer Center
🇺🇸Rochester, Minnesota, United States
Midwest Children's Cancer Center
🇺🇸Milwaukee, Wisconsin, United States
Miami Children's Hospital
🇺🇸Miami, Florida, United States
Phoenix Children's Hospital
🇺🇸Phoenix, Arizona, United States
Southern California Permanente Medical Group
🇺🇸Downey, California, United States
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, 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
Nemours Children's Clinic
🇺🇸Jacksonville, Florida, United States
Sacred Heart Cancer Center at Sacred Heart Hospital
🇺🇸Pensacola, Florida, United States
Saint Jude Midwest Affiliate
🇺🇸Peoria, Illinois, United States
CancerCare of Maine at Eastern Maine Medial Center
🇺🇸Bangor, Maine, United States
Southern Illinois University School of Medicine
🇺🇸Springfield, Illinois, United States
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Fairview University Medical Center - University Campus
🇺🇸Minneapolis, Minnesota, United States
SUNY Upstate Medical University Hospital
🇺🇸Syracuse, New York, United States
St. Barnabas Medical Center
🇺🇸Livingston, New Jersey, United States
Presbyterian Cancer Center at Presbyterian Hospital
🇺🇸Charlotte, North Carolina, United States
Texas Tech University Health Sciences Center School of Medicine
🇺🇸Amarillo, Texas, United States
St. Jude Children's Research Hospital
🇺🇸Memphis, Tennessee, United States
Cook Children's Medical Center - Fort Worth
🇺🇸Fort Worth, Texas, United States
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
🇺🇸Dallas, Texas, United States
Driscoll Children's Hospital
🇺🇸Corpus Christi, 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
Carilion Cancer Center of Western Virginia
🇺🇸Roanoke, Virginia, United States
Montreal Children's Hospital at McGill University Health Center
🇨🇦Montreal, Quebec, Canada
Children's Hospital Medical Center of Akron
🇺🇸Akron, Ohio, 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
Penn State Cancer Institute at Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Hackensack University Medical Center Cancer Center
🇺🇸Hackensack, New Jersey, United States
Kaiser Permanente Medical Center - Oakland
🇺🇸Sacramento, California, United States
Hollings Cancer Center at Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
C.S. Mott Children's Hospital at University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Children's Mercy Hospital
🇺🇸Kansas City, Missouri, United States
San Jorge Children's Hospital
🇵🇷Santurce, Puerto Rico
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
Albert Einstein Cancer Center at Albert Einstein College of Medicine
🇺🇸Bronx, New York, United States
University of Florida Shands Cancer Center
🇺🇸Gainesville, Florida, United States
Cancer Research Center of Hawaii
🇺🇸Honolulu, Hawaii, United States
Children's Hospital of Austin
🇺🇸Austin, Texas, United States
University of Wisconsin Comprehensive Cancer Center
🇺🇸Madison, Wisconsin, United States
Markey Cancer Center at University of Kentucky Chandler Medical Center
🇺🇸Lexington, Kentucky, United States