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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00467051
First received: April 25, 2007
Last updated: March 18, 2014
Last verified: March 2014
  Purpose

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: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
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 and after completion of protocol therapy ] [ Designated as safety issue: No ]
    Confidence intervals will be constructed according to the method of Chang and O'Brien.


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 ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 20
Study Start Date: November 2007
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
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Drug: ifosfamide
Given IV
Other Names:
  • Cyfos
  • Holoxan
  • IFF
  • IFX
  • IPP
Biological: filgrastim
Given IV or subcutaneously
Other Names:
  • G-CSF
  • Neupogen
Other: laboratory biomarker analysis
Optional correlative studies

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.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 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 ClinicalTrials.gov identifier: NCT00467051

  Show 35 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Principal Investigator: Carlos Rodriguez-Galindo Children's Oncology Group
  More Information

No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00467051     History of Changes
Other Study ID Numbers: AGCT0521, NCI-2009-00374, COG-AGCT0521, CDR0000542424, U10CA098543
Study First Received: April 25, 2007
Last Updated: March 18, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on October 23, 2014