Combination Chemotherapy in Treating Young Patients With Recurrent or Resistant Malignant Germ Cell Tumors
- Conditions
- Childhood Extracranial Germ Cell TumorChildhood Malignant Ovarian Germ Cell TumorChildhood Malignant Testicular Germ Cell TumorOvarian Yolk Sac TumorRecurrent Childhood Malignant Germ Cell TumorTesticular Mixed Choriocarcinoma and Yolk Sac TumorOvarian Embryonal CarcinomaRecurrent Malignant Testicular Germ Cell TumorOvarian ChoriocarcinomaRecurrent Ovarian Germ Cell Tumor
- Interventions
- Biological: FilgrastimOther: Laboratory Biomarker Analysis
- Registration Number
- NCT00467051
- Lead Sponsor
- Children's Oncology Group
- Brief Summary
This phase II trial is studying how well giving combination chemotherapy works in treating young patients with recurrent or resistant malignant germ cell tumors. Drugs used in chemotherapy, such as paclitaxel, ifosfamide, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.
- Detailed Description
PRIMARY OBJECTIVES:
I. Determine the response rate in pediatric patients with recurrent or resistant malignant germ cell tumors (GCT) treated with paclitaxel, ifosfamide, and carboplatin.
SECONDARY OBJECTIVES:
I. Determine the toxicity of this regimen in these patients. II. To Collect tissue for the tumor bank that will aid in the identification of the biological characteristics of recurrent GCT.
OUTLINE: This is a multicenter study.
Patients receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour on day 1 and ifosfamide IV over 1 hour on days 1-5. Beginning on day 6, patients receive filgrastim (G-CSF) subcutaneously or IV once daily until blood count returns to normal. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed periodically for up to 5 years.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 20
-
Histologically confirmed (at original diagnosis) extracranial germ cell tumor (GCT) containing 1 of the following malignant elements:
- Yolk sac tumor (endodermal sinus tumor)
- Choriocarcinoma
- Embryonal carcinoma
-
Meets 1 of the following disease criteria:
- Recurrent malignant disease
- Chemotherapy-resistant disease
- Relapsed disease
- Disease refractory to conventional therapy
-
Measurable disease
-
Must have received a prior first-line chemotherapy regimen that included cisplatin
-
Patients with tumor marker (AFP and/or BHCG) elevation alone or bone scan findings alone are not eligible*
-
Patients with immature teratoma (any grade), germinoma, sex-cord stromal tumors, or recurrent GCT previously treated with surgery alone are not eligible
-
Karnofsky performance status (PS) 50-100% (age > 16 years) OR Lansky PS 50-100% (age ≤ 16 years) OR ECOG PS 0-2
-
Life expectancy ≥ 8 weeks
-
Absolute neutrophil count ≥ 750/mm³
-
Platelet count ≥ 75,000/mm³ (transfusion independent)
-
Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR creatinine normal based on age/gender, as defined by the following:
- ≤ 0.4 mg/dL (1 month to < 6 months of age)
- ≤ 0.5 mg/dL (6 months to < 1 year of age)
- ≤ 0.6 mg/dL (1 to < 2 years of age)
- ≤ 0.8 mg/dL (2 to < 6 years of age)
- ≤ 1.0 mg/dL (6 to < 10 years of age)
- ≤ 1.2 mg/dL (10 to < 13 years of age)
- ≤ 1.4 mg/dL (13 to ≥ 16 years of age) (female)
- ≤ 1.5 mg/dL (13 to < 16 years of age) (male)
- ≤ 1.7 mg/dL (≥ 16 years of age) (male)
-
Bilirubin ≤ 1.5 times upper limit of normal (ULN) for age
-
ALT < 2.5 times ULN for age
-
Shortening fraction ≥ 27% by echocardiogram OR ejection fraction ≥ 50% by gated radionuclide study
-
No dyspnea at rest
-
No exercise intolerance
-
Pulse oximetry > 94% (if there is clinical indication for determination)
-
Patients with seizure disorder are eligible provided they are on non-enzyme inducing anticonvulsants and seizures are well controlled
-
No CNS toxicity > grade 2
-
No active graft-versus-host disease
-
No allergy to Cremophor EL or castor oil
-
Not pregnant or nursing
-
Negative pregnancy test
-
Fertile patients must use effective contraception
-
No other concurrent chemotherapy or immunomodulating agents
-
Recovered from prior chemotherapy, immunotherapy, or radiotherapy
-
At least 1 week since prior growth factors (2 weeks for pegfilgrastim)
-
At least 1 week since prior biologic therapy
-
At least 2 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosourea)
-
At least 2 weeks since prior local palliative radiotherapy (i.e., small port)
-
At least 6 months since prior craniospinal radiotherapy or radiotherapy to ≥ 50% of pelvis
-
At least 6 weeks since other prior substantial bone marrow radiotherapy
-
At least 6 months since prior allogeneic stem cell transplantation
-
Concurrent radiotherapy to localized painful lesions allowed provided at least 1 measurable lesion is not irradiated
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment (chemotherapy, biological therapy) Filgrastim Patients receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour on day 1 and ifosfamide IV over 1 hour on days 1-5. Beginning on day 6, patients receive filgrastim (G-CSF) subcutaneously or IV once daily until blood count returns to normal. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Treatment (chemotherapy, biological therapy) Laboratory Biomarker Analysis Patients receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour on day 1 and ifosfamide IV over 1 hour on days 1-5. Beginning on day 6, patients receive filgrastim (G-CSF) subcutaneously or IV once daily until blood count returns to normal. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Treatment (chemotherapy, biological therapy) Carboplatin Patients receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour on day 1 and ifosfamide IV over 1 hour on days 1-5. Beginning on day 6, patients receive filgrastim (G-CSF) subcutaneously or IV once daily until blood count returns to normal. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Treatment (chemotherapy, biological therapy) Ifosfamide Patients receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour on day 1 and ifosfamide IV over 1 hour on days 1-5. Beginning on day 6, patients receive filgrastim (G-CSF) subcutaneously or IV once daily until blood count returns to normal. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Treatment (chemotherapy, biological therapy) Paclitaxel Patients receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour on day 1 and ifosfamide IV over 1 hour on days 1-5. Beginning on day 6, patients receive filgrastim (G-CSF) subcutaneously or IV once daily until blood count returns to normal. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
- Primary Outcome Measures
Name Time Method Response Rate as Measured by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria At baseline (day 1) and after completion of protocol therapy (2 cycles or 42 days) Patients who demonstrate a PR or CR, as defined below, will be considered as responders. RECIST criteria: CR (complete response) = disappearance of all target lesions, PR (partial response) = 30% decrease in the sum of the longest diameter of target lesions, PD (progressive disease) = 20% increase in the sum of the longest diameter of target lesions and SD (stable disease) = small changes that do not meet above criteria.
- Secondary Outcome Measures
Name Time Method The Number of Patients Who Experience at Least One Grade 3 or Higher CTC Version 4 Toxicity. Two cycles of chemotherapy; expected to be 42 days of treatment.
Trial Locations
- Locations (95)
Cedars Sinai Medical Center
🇺🇸Los Angeles, California, United States
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
Palmetto Health Richland
🇺🇸Columbia, South Carolina, United States
West Virginia University Charleston Division
🇺🇸Charleston, West Virginia, United States
Rainbow Babies and Childrens Hospital
🇺🇸Cleveland, Ohio, United States
The University of Arizona Medical Center-University Campus
🇺🇸Tucson, Arizona, United States
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
Miller Children's and Women's Hospital Long Beach
🇺🇸Long Beach, California, United States
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Lucile Packard Children's Hospital Stanford University
🇺🇸Palo Alto, California, United States
Kaiser Permanente Downey Medical Center
🇺🇸Downey, California, United States
Harbor-University of California at Los Angeles Medical Center
🇺🇸Torrance, California, United States
University of Connecticut
🇺🇸Farmington, Connecticut, United States
Alfred I duPont Hospital for Children
🇺🇸Wilmington, Delaware, United States
Connecticut Children's Medical Center
🇺🇸Hartford, Connecticut, United States
MedStar Georgetown University Hospital
🇺🇸Washington, District of Columbia, United States
Lee Memorial Health System
🇺🇸Fort Myers, Florida, United States
Nemours Children's Clinic-Jacksonville
🇺🇸Jacksonville, Florida, United States
Florida Hospital Orlando
🇺🇸Orlando, Florida, United States
Nemours Children's Clinic - Pensacola
🇺🇸Pensacola, Florida, United States
Nemours Children's Clinic - Orlando
🇺🇸Orlando, Florida, United States
Johns Hopkins All Children's Hospital
🇺🇸Saint Petersburg, Florida, United States
Sacred Heart Hospital
🇺🇸Pensacola, Florida, United States
Children's Healthcare of Atlanta - Egleston
🇺🇸Atlanta, Georgia, United States
Saint Mary's Hospital
🇺🇸West Palm Beach, Florida, United States
Emory University Hospital/Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
Lurie Children's Hospital-Chicago
🇺🇸Chicago, Illinois, United States
University of Illinois
🇺🇸Chicago, Illinois, United States
Advocate Children's Hospital-Oak Lawn
🇺🇸Oak Lawn, Illinois, United States
Saint Jude Midwest Affiliate
🇺🇸Peoria, Illinois, United States
University of Kentucky/Markey Cancer Center
🇺🇸Lexington, Kentucky, United States
Norton Children's Hospital
🇺🇸Louisville, Kentucky, United States
Tulane University Health Sciences Center
🇺🇸New Orleans, Louisiana, United States
Children's Hospital New Orleans
🇺🇸New Orleans, Louisiana, United States
Sinai Hospital of Baltimore
🇺🇸Baltimore, Maryland, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
🇺🇸Baltimore, Maryland, United States
Helen DeVos Children's Hospital at Spectrum Health
🇺🇸Grand Rapids, Michigan, United States
Spectrum Health at Butterworth Campus
🇺🇸Grand Rapids, Michigan, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
The Childrens Mercy Hospital
🇺🇸Kansas City, Missouri, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
🇺🇸New Brunswick, New Jersey, United States
Saint Joseph's Regional Medical Center
🇺🇸Paterson, New Jersey, United States
Overlook Hospital
🇺🇸Summit, New Jersey, United States
University of New Mexico Cancer Center
🇺🇸Albuquerque, New Mexico, United States
Albany Medical Center
🇺🇸Albany, New York, United States
Montefiore Medical Center - Moses Campus
🇺🇸Bronx, New York, United States
Columbia University/Herbert Irving Cancer Center
🇺🇸New York, New York, United States
State University of New York Upstate Medical University
🇺🇸Syracuse, New York, United States
UNC Lineberger Comprehensive Cancer Center
🇺🇸Chapel Hill, North Carolina, United States
Children's Hospital Medical Center of Akron
🇺🇸Akron, Ohio, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
Dayton Children's Hospital
🇺🇸Dayton, Ohio, United States
Penn State Milton S Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Penn State Children's Hospital
🇺🇸Hershey, Pennsylvania, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
East Tennessee Childrens Hospital
🇺🇸Knoxville, Tennessee, United States
St. Jude Children's Research Hospital
🇺🇸Memphis, Tennessee, United States
Driscoll Children's Hospital
🇺🇸Corpus Christi, Texas, United States
Medical City Dallas Hospital
🇺🇸Dallas, Texas, United States
Cook Children's Medical Center
🇺🇸Fort Worth, Texas, United States
Covenant Children's Hospital
🇺🇸Lubbock, Texas, United States
Children's Hospital of The King's Daughters
🇺🇸Norfolk, Virginia, United States
Carilion Clinic Children's Hospital
🇺🇸Roanoke, Virginia, United States
University of Alberta Hospital
🇨🇦Edmonton, Alberta, Canada
British Columbia Children's Hospital
🇨🇦Vancouver, British Columbia, Canada
IWK Health Centre
🇨🇦Halifax, Nova Scotia, Canada
McMaster Children's Hospital at Hamilton Health Sciences
🇨🇦Hamilton, Ontario, Canada
Children's Hospital of Eastern Ontario
🇨🇦Ottawa, Ontario, Canada
Centre Hospitalier Universitaire Sainte-Justine
🇨🇦Montreal, Quebec, Canada
Centre Hospitalier Universitaire de Quebec
🇨🇦Quebec, Canada
San Jorge Children's Hospital
🇵🇷San Juan, Puerto Rico
Massachusetts General Hospital Cancer Center
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
🇺🇸Houston, Texas, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
🇺🇸Miami, Florida, United States
Indiana University/Melvin and Bren Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
Riley Hospital for Children
🇺🇸Indianapolis, Indiana, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
🇺🇸Minneapolis, Minnesota, 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
University of Hawaii Cancer Center
🇺🇸Honolulu, Hawaii, United States
CancerCare Manitoba
🇨🇦Winnipeg, Manitoba, Canada
Sanford Broadway Medical Center
🇺🇸Fargo, North Dakota, United States
Princess Margaret Hospital for Children
🇦🇺Perth, Western Australia, Australia
UCSF Medical Center-Mount Zion
🇺🇸San Francisco, California, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
🇺🇸Denver, Colorado, United States
Saint Joseph's Hospital/Children's Hospital-Tampa
🇺🇸Tampa, Florida, United States
Carolinas Medical Center/Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
UCSF Medical Center-Parnassus
🇺🇸San Francisco, California, United States