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

This study has been completed.
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group Identifier:
First received: April 25, 2007
Last updated: February 7, 2017
Last verified: February 2017
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 Intervention 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

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: Treatment of Recurrent or Resistant Pediatric Malignant Germ Cell Tumors With Paclitaxel, Ifosfamide and Carboplatin

Resource links provided by NLM:

Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • 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:
  • Toxicity as Measured by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events ( CTCAE) Version 4.0 [ Time Frame: During and after completion of study treatment ]
    All patients who experience any grade 2 or higher toxicity at any time during the two treatment cycles or who receive at least all required Ifosfamide therapy after enrollment will be considered evaluable for toxicity. The descriptions and grading scales found in the revised NCI CTCAE version 4 will be used.

Enrollment: 20
Study Start Date: November 2007
Study Completion Date: March 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.


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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00467051

  Show 35 Study Locations
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Principal Investigator: Carlos Rodriguez-Galindo, MD Children's Oncology Group
  More Information

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 ( US NIH Grant/Contract Award Number )
Study First Received: April 25, 2007
Results First Received: March 11, 2015
Last Updated: February 7, 2017

Additional relevant MeSH terms:
Neoplasms, Germ Cell and Embryonal
Testicular Neoplasms
Carcinoma, Embryonal
Endodermal Sinus Tumor
Ovarian Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Endocrine Gland Neoplasms
Neoplasms by Site
Genital Neoplasms, Male
Urogenital Neoplasms
Genital Diseases, Male
Endocrine System Diseases
Testicular Diseases
Gonadal Disorders
Trophoblastic Neoplasms
Pregnancy Complications, Neoplastic
Pregnancy Complications
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Isophosphamide mustard processed this record on May 25, 2017