Chemotherapy Followed by Radiation Therapy in Treating Younger Patients With Newly Diagnosed Localized Central Nervous System Germ Cell Tumors
Condition: Central Nervous System Nongerminomatous Germ Cell Tumor; Childhood Central Nervous System Germinoma
MeSH terms: Neoplasms, Germ Cell and Embryonal; Germinoma
Intervention: 3-Dimensional Conformal Radiation Therapy; Carboplatin; Etoposide; Ifosfamide; Intensity-Modulated Radiation Therapy
Intervention description: Undergo 3D-CRT; Given IV; Given IV; Given IV; Undergo IMRT
Intervention MeSH terms: Carboplatin; Etoposide; Etoposide phosphate; Ifosfamide; Isophosphamide mustard; Podophyllotoxin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 262.0
Sex: All
Minimum age: 3 Years
Maximum age: 21 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well chemotherapy followed by radiation therapy work in
      treating younger patients with newly diagnosed central nervous system germ cell tumors that
      have not spread to other parts of the brain, spinal canal, or body (localized). Drugs used as
      chemotherapy, such as carboplatin, etoposide, and ifosfamide, work in different ways to stop
      the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by
      stopping them from spreading. Radiation therapy uses high-energy x rays to kill tumor cells.
      Giving chemotherapy followed by radiation therapy may kill more tumor cells.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must be newly diagnosed with localized primary CNS NGGCT (Stratum 1) or
             localized primary CNS germinoma (Stratum 2); germ cell tumors located in the
             suprasellar, pineal, bifocal (pineal + suprasellar) and ventricles are eligible;
             tumors present in the above mentioned locations and with unifocal parenchymal
             extension are eligible

               -  Stratum 1(NGGCT): Patients must have one of the following criteria:

                    -  Patients with serum and/or CSF hCGbeta > 100 mIU/mL or any elevation of
                       serum and/or CSF alpha-fetoprotein (AFP) > 10 ng/mL or greater than the
                       institutional normal are eligible, irrespective of biopsy results

                    -  Patients with any of the following elements on biopsy/resection are
                       eligible, irrespective of serum and/or CSF hCGbeta and AFP levels:
                       endodermal sinus tumor (yolk sac), embryonal carcinoma, choriocarcinoma,
                       malignant/immature teratoma, and mixed GCT with malignant GCT elements

               -  Stratum 2 (Germinoma): Patients must have both serum and CSF markers obtained
                  (unless obtaining CSF is medically contraindicated) and must have one of the
                  following criteria to be eligible:

                    -  Patients with institutional normal AFP (or =< 10 ng/mL if no institutional
                       normal exists) in both serum and CSF (unless medically contraindicated) AND
                       hCGbeta 5 to =< 50 mIU/mL in serum and/or CSF (unless medically
                       contraindicated) (only 1 is required to be elevated) are eligible; no
                       histologic confirmation required

                    -  Patients with bifocal (pineal + suprasellar) involvement or pineal lesion
                       with diabetes insipidus (D1) AND hCGbeta =< 100 mIU/mL in serum and/or CSF
                       AND institutional normal AFP (or =< 10 ng/mL if no institutional normal
                       exists) in both serum and CSF (unless medically contraindicated) are
                       eligible; no histologic confirmation required

                    -  Patients with histologically confirmed germinoma or germinoma mixed with
                       mature teratoma and hCGbeta =< 100 mIU/mL in serum and/or CSF and
                       institutional normal AFP (or =< 10 ng/mL if no institutional normal exists)
                       in both serum and CSF (unless medically contraindicated) are eligible

          -  All patients must have a cranial MRI with and without gadolinium at diagnosis/prior to
             enrollment; if surgical resection is performed, patients must have pre-operative and
             post-operative cranial MRI with and without gadolinium; the post-operative brain MRI
             should be obtained within 72 hours of surgery; if patient has a biopsy only,
             post-operative cranial MRI is recommended but not required; all patients must have a
             spine MRI with gadolinium obtained at diagnosis/prior to enrollment; Note: if the
             spine study is performed for the first time after surgical resection or biopsy, it is
             recommended to be obtained with and without gadolinium

          -  Lumbar CSF must be obtained prior to study enrollment unless medically
             contraindicated; if a patient undergoes surgery and lumbar CSF cannot be obtained at
             this time, then it should be performed at least 10 days following surgery before study
             enrollment; false positive cytology can occur within 10 days of surgery; Note:
             patients with positive CSF cytology obtained prior to 10 days after surgery may have
             cytology repeated to determine eligibility

          -  Patients must have CSF tumor markers obtained prior to enrollment unless medically
             contraindicated; ventricular CSF obtained at the time of CSF diversion procedure (if
             performed) is acceptable for tumor markers but lumbar CSF is preferred; in case CSF
             diversion and biopsy/surgery are combined, CSF tumor markers should be collected first

          -  Patients must be enrolled on ALTE07C1 prior to enrollment on ACNS1123; patients must
             be enrolled within 31 days of definitive diagnostic surgery (day 0) or clinical
             diagnosis

          -  Peripheral absolute neutrophil count (ANC) >= 1,000/uL

          -  Platelet count >= 100,000/uL (transfusion independent)

          -  Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions)

          -  Creatinine clearance or radioisotope glomular filtration rate (GFR) >= 70 mL/min/1.73
             m^2 OR serum creatinine based on age/gender as follows:

               -  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)

               -  1.5 mg/dL (male) and 1.4 mg/dL (female) (13 to < 16 years of age)

               -  1.7 mg/dL (male) and 1.4 mg/dL (female) (>= 16 years of age)

          -  Total bilirubin =< 1.5 times upper limit of normal (ULN) for age

          -  Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and
             serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5
             times ULN

          -  Patients with seizure disorder may be enrolled if well controlled

          -  Patients must not be in status, coma, or assisted ventilation prior to study
             enrollment

        Exclusion Criteria:

          -  Patients with mature teratoma or completely resected immature teratoma with normal
             tumor markers are not eligible

          -  Patients with tumors located outside the ventricles (basal ganglia, thalamus) are not
             eligible

          -  Patients with metastatic disease by cranial or spinal MRI evaluation or CSF cytology
             (unless medically contraindicated) are not eligible

          -  Patients must not have received any prior tumor-directed therapy other than surgical
             intervention and corticosteroids

          -  Female patients who are pregnant are ineligible

          -  Lactating females are not eligible unless they have agreed not to breastfeed their
             infants

          -  Female patients of childbearing potential are not eligible unless a negative pregnancy
             test result has been obtained

          -  Sexually active patients of reproductive potential are not eligible unless they have
             agreed to use an effective contraceptive method for the duration of their study
             participation

          -  All patients and/or their parents or legal guardians must sign a written informed
             consent

          -  All institutional, Food and Drug Administration (FDA), and National Cancer Institute
             (NCI) requirements for human studies must be met