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Radiation Therapy Compared With Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Primary Central Nervous System (CNS) Germ Cell Tumor

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: NCT00085098
Recruitment Status : Completed
First Posted : June 11, 2004
Results First Posted : November 6, 2013
Last Update Posted : September 7, 2018
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Brief Summary:

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether radiation therapy alone is as effective as chemotherapy plus radiation therapy in treating germ cell tumor.

PURPOSE: This randomized phase III trial is studying radiation therapy alone to see how well it works compared to chemotherapy and radiation therapy in treating patients with newly diagnosed primary CNS germ cell tumor.

Condition or disease Intervention/treatment Phase
Brain Tumor Central Nervous System Tumor Biological: filgrastim Drug: carboplatin Drug: cisplatin Drug: cyclophosphamide Drug: etoposide Radiation: radiation therapy Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Radiotherapy Alone Versus Chemotherapy Followed By Response-Based Radiotherapy For Newly Diagnosed Primary CNS Germinoma
Study Start Date : January 2007
Actual Primary Completion Date : May 2009
Actual Study Completion Date : May 2009

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Regimen A (radiotherapy only)
Within 52 days of surgery, patients will undergo standard-dose radiation therapy 5 days a week for approximately 5-6 weeks.
Radiation: radiation therapy
Patients undergo radiotherapy 5 days a week

Experimental: Regimen B (chemotherapy plus radiotherapy)

Courses 1 and 2: Patients receive carboplatin IV over 1 hour on days 1 and 2 and etoposide IV over 2 hours on days 1-3. Treatment repeats every 21 days for 2 courses.

Within 3 weeks of completing chemotherapy, patients with CR undergo low-dose radiation therapy 5 days a week for 5 weeks. Patients with MRD, a PR, or SD receive chemotherapy courses 3 and 4 as outlined below.

Courses 3 and 4: Patients receive cisplatin IV over 6 hours on day 1, cyclophosphamide IV over 1 hour on days 2 and 3, and filgrastim (G-CSF), subcutaneous (SC) or IV beginning on day 4 and continuing until blood counts recover.

Treatment repeats every 21 days for 2 courses. Patients achieving a CR or MRD proceed to reduced-dose radiotherapy. Patients with a PR, SD, or progressive disease (PD) are restaged and may undergo standard radiation therapy as in regimen A. Reduced-dose radiation therapy: Within 6 weeks of starting course 4, patients undergo lower-dose radiation therapy once daily on days 1-5 for 5 weeks

Biological: filgrastim
Given by infusion or injection
Other Names:
  • Granulocyte Colony-Stimulating Factor
  • r-metHuG-CSF
  • G-CSF
  • Neupogen
  • NSC #61462

Drug: carboplatin
Given IV over 1 hour
Other Names:
  • Paraplatin
  • NSC #241240

Drug: cisplatin
Given IV over 6 hours
Other Names:
  • Cis-diamminedichloroplatinum II
  • Platinol-AQ
  • NSC #119875

Drug: cyclophosphamide
Given IV over 1 hour
Other Names:
  • Cytoxan
  • NSC #26271

Drug: etoposide
Given IV over 2 hours
Other Names:
  • VePesid
  • Etopophos
  • VP-16
  • NSC #141540

Radiation: radiation therapy
Patients undergo radiotherapy 5 days a week

Primary Outcome Measures :
  1. Event-free Survival [ Time Frame: Study enrollment until date of earliest qualifying event (QE), date last known to be QE-free if the patient is followed for less than three years and is QE-free at the time of analysis, or 3 years if the patient is QE-free at 3 years ]

    Data will be summarized as number of patients in the following categories at the time of data cutoff for analyses of 3-year EFS: 1)Experienced a qualifying event (QE) (see below);2)Event-free through 3 years of follow-up;3)Event-free until data cutoff (if less than 3 years of follow-up);4)Withdrew from study;5)Lost to follow-up.

    QEs: 1)disease progression, defined as increase >= 40% in tumor volume or >= 25% in tumor area of target lesions;2)development of new lesions;3)occurrence of a second malignant neoplasm, defined as a malignancy with different histological type from trial-qualifying diagnosis;4)death from any cause.

    Stat. analyses will be based on time from enrollment to the earliest of: 1)occurrence of any of the QEs;2)withdrawal from study or lost to follow-up;3)completion of three years of follow-up event-free;4)data cutoff for completion of the statistical analyses for the protocol's primary objective.

    NOTE: Reported data are through May 2009 (see Caveats section).

Secondary Outcome Measures :
  1. Number of Participants With a Response to Regimen B [ Time Frame: 5 years from beginning of treatment ]
    To assess the complete response rate to pre-radiotherapy chemotherapy (Reg B only). Response was determined after completing 2-4 cycles of chemotherapy on Reg B. Complete Response (CR) is defined as disappearance of all target lesions.

  2. Toxicity and Safety as Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 [ Time Frame: From the beginning of treatment, assessed up to 5 years ]
    The analysis of toxicity will focus on estimating the rates of key acute and subacute toxicity occurring during the first induction chemotherapy. The list of toxicities of interest include Anemia or Febrile Neutropenia; Nausea or Vomiting; Infections and Infestations; Neutrophil or White blood count decrease; and Hypokalemia or Hyponatremia

  3. Quality of Life (QOL) and Neurocognitive Assessment (NP) [ Time Frame: 2 years from beginning of treatment ]
    The primary endpoints for QOL and NP assessments will be the global scale value from each of these instruments at the two-year time point. Analyses of subscales (if they exist) and of assessments at other times will be of secondary interest. It is assumed that scale values are standardized to a reference normal population. The scores range from 0 to 100 with higher score reflecting better QoL or neurocognitive assessment.

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Ages Eligible for Study:   3 Years to 25 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically confirmed primary CNS pure germ cell tumor

    • Diagnosed within the past 31 days
  • Meets any 1 OR none (i.e., M0 [localized disease]) of the following staging criteria:

    • M+ (disseminated disease)

      • Leptomeningeal or intraventricular metastases visualized on MRI scans of the brain and spine
      • Clumps of tumor cells on lumbar cerebrospinal fluid (CSF) cytology
      • Visible tumor studding the walls of the lateral or third ventricles noted during endoscopy or surgery
      • Primary tumor arising within the parenchyma of the brain, brainstem, or spinal cord
      • Measurable multi-focal tumors arising in both the pineal and suprasellar regions (i.e., multiple midline tumors)
      • Infiltrative, intra-axial extension on brain MRI > 1 cm beyond enhancing tumor
    • Modified M+ (occult multi-focal disease)

      • M0 at diagnosis with a localized pineal region tumor with signs and symptoms of diabetes insipidus without measurable disease in the suprasellar region
  • Lumbar CSF assay meeting criteria for the following marker profiles:

    • Serum and CSF beta human chorionic gonadotropin (β-HCG) ≤ 50 IU/dL
    • Serum alpha fetoprotein (AFP) ≤ 10 IU/L AND ≤ institutional norm
    • CSF AFP ≤ 2.0 IU/L AND ≤ institutional norm



  • 3 to 25

Performance status

  • Not specified

Life expectancy

  • Not specified


  • Absolute neutrophil count > 1,000/mm^3
  • Platelet count > 100,000/mm^3 (transfusion independent)
  • Hemoglobin > 10.0 g/dL (transfusion allowed)


  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5 times ULN


  • Creatinine adjusted according to age as follows*:

    • No greater than 0.4 mg/dL (≤ 5 months)
    • No greater than 0.5 mg/dL (6 months -11 months)
    • No greater than 0.6 mg/dL (1 year-23 months)
    • No greater than 0.8 mg/dL (2 years-5 years)
    • No greater than 1.0 mg/dL (6 years-9 years)
    • No greater than 1.2 mg/dL (10 years-12 years)
    • No greater than 1.4 mg/dL (13 years and over [female])
    • No greater than 1.5 mg/dL (13 years to 15 years [male])
    • No greater than 1.7 mg/dL (16 years and over [male]) AND
  • Creatinine clearance OR radioisotope glomerular filtration rate > 70 mL/min


  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Euthyroid (with or without levothyroxine sodium therapy) as determined by normal T4 ± thyroid-stimulating hormone levels*
  • Diabetes insipidus allowed provided patient is relatively stable on desmopressin acetate
  • Normal endogenous cortisol function*
  • Adequate antidiuretic hormone reserves* NOTE: *Unless receiving replacement therapy


Biologic therapy

  • Not specified


  • Not specified

Endocrine therapy

  • Concurrent replacement hormones allowed (e.g., corticosteroids, levothyroxine sodium, and desmopressin acetate)


  • Not specified


  • Prior surgery for germ cell tumor allowed


  • No other prior therapy for germ cell tumor
  • Concurrent anticonvulsants allowed

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): NCT00085098

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Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
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Study Chair: Jeffrey C. Allen, MD NYU Langone Health
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Responsible Party: Children's Oncology Group Identifier: NCT00085098    
Other Study ID Numbers: ACNS0232
CDR0000367294 ( Other Identifier: Clinical )
COG-ACNS0232 ( Other Identifier: Children's Oncology Group )
First Posted: June 11, 2004    Key Record Dates
Results First Posted: November 6, 2013
Last Update Posted: September 7, 2018
Last Verified: August 2018
Keywords provided by Children's Oncology Group:
childhood central nervous system germ cell tumor
Additional relevant MeSH terms:
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Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms by Site
Nervous System Diseases
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Adjuvants, Immunologic