Radiation Therapy Compared With Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Primary Central Nervous System (CNS) Germ Cell Tumor
Condition: Brain Tumor; Central Nervous System Tumor
MeSH terms: Neoplasms; Nervous System Neoplasms; Central Nervous System Neoplasms
Intervention: filgrastim; carboplatin; cisplatin; cyclophosphamide; etoposide; radiation therapy
Intervention description: Given by infusion or injection; Given IV over 1 hour; Given IV over 6 hours; Given IV over 1 hour; Given IV over 2 hours; Patients undergo radiotherapy 5 days a week
Intervention MeSH terms: Cyclophosphamide; Cisplatin; Carboplatin; Etoposide; Lenograstim
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 3 Years
Maximum age: 25 Years
Healthy volunteers: No
Keywords: childhood central nervous system germ cell tumor

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.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  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

        PATIENT CHARACTERISTICS:

        Age

          -  3 to 25

        Performance status

          -  Not specified

        Life expectancy

          -  Not specified

        Hematopoietic

          -  Absolute neutrophil count > 1,000/mm^3

          -  Platelet count > 100,000/mm^3 (transfusion independent)

          -  Hemoglobin > 10.0 g/dL (transfusion allowed)

        Hepatic

          -  Bilirubin ≤ 1.5 times upper limit of normal (ULN)

          -  aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5 times ULN

        Renal

          -  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

        Other

          -  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

        PRIOR CONCURRENT THERAPY:

        Biologic therapy

          -  Not specified

        Chemotherapy

          -  Not specified

        Endocrine therapy

          -  Concurrent replacement hormones allowed (e.g., corticosteroids, levothyroxine sodium,
             and desmopressin acetate)

        Radiotherapy

          -  Not specified

        Surgery

          -  Prior surgery for germ cell tumor allowed

        Other

          -  No other prior therapy for germ cell tumor

          -  Concurrent anticonvulsants allowed