Combination Chemotherapy in Treating Young Patients With Recurrent or Resistant Malignant Germ Cell Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00467051
Recruitment Status : Completed
First Posted : April 27, 2007
Results First Posted : March 20, 2015
Last Update Posted : December 12, 2017
National Cancer Institute (NCI)
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Childhood Extracranial Germ Cell Tumor Childhood Extragonadal Germ Cell Tumor Childhood Malignant Ovarian Germ Cell Tumor Childhood Malignant Testicular Germ Cell Tumor Ovarian Choriocarcinoma Ovarian Embryonal Carcinoma Ovarian Yolk Sac Tumor Recurrent Childhood Malignant Germ Cell Tumor Recurrent Malignant Testicular Germ Cell Tumor Recurrent Ovarian Germ Cell Tumor Testicular Choriocarcinoma Testicular Choriocarcinoma and Embryonal Carcinoma Testicular Choriocarcinoma and Yolk Sac Tumor Testicular Embryonal Carcinoma Testicular Embryonal Carcinoma and Yolk Sac Tumor Testicular Yolk Sac Tumor Drug: paclitaxel Drug: carboplatin Drug: ifosfamide Biological: filgrastim Other: laboratory biomarker analysis Phase 2

Detailed Description:


I. Determine the response rate in pediatric patients with recurrent or resistant malignant germ cell tumors (GCT) treated with paclitaxel, ifosfamide, and carboplatin.


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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Treatment of Recurrent or Resistant Pediatric Malignant Germ Cell Tumors With Paclitaxel, Ifosfamide and Carboplatin
Study Start Date : November 2007
Actual Primary Completion Date : March 2012
Actual Study Completion Date : March 2012

Arm Intervention/treatment
Experimental: Treatment (chemotherapy, biological therapy)
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.
Drug: paclitaxel
Given IV dosage 135 mg/m2/dose
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol

Drug: carboplatin
Given IV dosage in mg/m2 = Target AUC (mg•min/mL) x [(0.93 x GFR mL/min/m2) + 15]= 6.5 x [(0.93 x GFR mL/min/m2) + 15]. (BSA = body surface area in square meters). GFR is reported in institutions as "uncorrected" or "raw" (not normalized to BSA) or "corrected." This number needs to be converted to GFR in mL/min/m2.
Other Names:
  • Carboplat
  • JM-8
  • Paraplat
  • Paraplatin

Drug: ifosfamide
Given IV dosage 1800 mg/m2/dose
Other Names:
  • Cyfos
  • Holoxan
  • IFF
  • IFX
  • IPP

Biological: filgrastim
Given IV or subcutaneously dosage 1,080mg/m2/day divided to three equal doses of 360mg/m2
Other Names:
  • G-CSF
  • Neupogen

Other: laboratory biomarker analysis
Optional correlative studies

Primary Outcome Measures :
  1. Response Rate as Measured by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria [ Time Frame: 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 :
  1. The Number of Patients Who Experience at Least One Grade 3 or Higher CTC Version 4 Toxicity. [ Time Frame: Two cycles of chemotherapy; expected to be 42 days of treatment. ]

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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 Central Nervous System (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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00467051

  Hide Study Locations
United States, Arizona
University of Arizona Health Sciences Center
Tucson, Arizona, United States, 85724
United States, California
Southern California Permanente Medical Group
Downey, California, United States, 90242
Children's Hospital Los Angeles
El Pueblo De Nuestra Señora De Los Ángeles De Porciúncula, California, United States, 90027
University of California San Francisco Medical Center-Parnassus
Frisco, California, United States, 94143
Miller Children's Hospital
Long Beach, California, United States, 90806
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, United States, 94304
United States, Colorado
Children's Hospital Colorado
Aurora, Colorado, United States, 80045
United States, Connecticut
Connecticut Children's Medical Center
Hartford, Connecticut, United States, 06106
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010
Lombardi Comprehensive Cancer Center at Georgetown University
Washington, District of Columbia, United States, 20057
United States, Georgia
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, United States, 30322
United States, Illinois
Saint Jude Midwest Affiliate
Peoria, Illinois, United States, 61602
United States, Indiana
Indiana University Medical Center
Indianapolis, Indiana, United States, 46202
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21287-8936
United States, Massachusetts
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Michigan
Helen DeVos Children's Hospital at Spectrum Health
Grand Rapids, Michigan, United States, 49503
United States, Missouri
The Childrens Mercy Hospital
Kansas City, Missouri, United States, 64108
United States, New Mexico
University of New Mexico Cancer Center
Albuquerque, New Mexico, United States, 87106
United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10467-2490
United States, North Dakota
Sanford Medical Center-Fargo
Fargo, North Dakota, United States, 58122
United States, Ohio
Children's Hospital Medical Center of Akron
Akron, Ohio, United States, 44308
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
United States, Pennsylvania
Penn State Hershey Children's Hospital
Hershey, Pennsylvania, United States, 17033
Children's Hospital of Pittsburgh of UPMC
Pittsburg, Pennsylvania, United States, 15224
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Texas
Covenant Children's Hospital
Lubbock, Texas, United States, 79410
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78229-3900
Methodist Children's Hospital of South Texas
San Antonio, Texas, United States, 78229
United States, Virginia
Carilion Clinic Children's Hospital
Roanoke, Virginia, United States, 24014
Australia, Western Australia
Princess Margaret Hospital for Children
Perth, Western Australia, Australia, 6008
Canada, Ontario
Chedoke-McMaster Hospitals
Hamilton, Ontario, Canada, L8S 4L8
Children's Hospital of Eastern Ontario
Ottawa, Ontario, Canada, K1H 8L1
Canada, Quebec
Centre Hospitalier Universitaire de Quebec
Ste-Foy, Quebec, Canada, G1V 4G2
Puerto Rico
San Jorge Children's Hospital
Santurce, Puerto Rico, 00912
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Principal Investigator: Carlos Rodriguez-Galindo, MD Children's Oncology Group

Responsible Party: Children's Oncology Group Identifier: NCT00467051     History of Changes
Other Study ID Numbers: AGCT0521
NCI-2009-00374 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
COG-AGCT0521 ( Other Identifier: Children's Oncology Group )
CDR0000542424 ( Other Identifier: Clinical )
U10CA098543 ( U.S. NIH Grant/Contract )
First Posted: April 27, 2007    Key Record Dates
Results First Posted: March 20, 2015
Last Update Posted: December 12, 2017
Last Verified: November 2017

Additional relevant MeSH terms:
Neoplasms, Germ Cell and Embryonal
Ovarian Neoplasms
Testicular Neoplasms
Carcinoma, Embryonal
Endodermal Sinus Tumor
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Genital Neoplasms, Male
Genital Diseases, Male
Testicular Diseases
Trophoblastic Neoplasms
Pregnancy Complications, Neoplastic
Pregnancy Complications
Isophosphamide mustard