Chemotherapy Followed by Radiation Therapy in Treating Younger Patients With Newly Diagnosed Localized Central Nervous System Germ Cell Tumors

• 3-year PFS rate with NGGCT [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  Kaplan-Meier estimates will be provided.
• PFS distribution of localized CNS germinoma [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  Kaplan-Meier estimates will be provided.
• Neurocognitive function using the ALTE07C1 protocol [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]

• 3-year PFS rate with NGGCT [ Designated as safety issue: No ]
• PFS distribution of localized CNS germinoma at 3 years [ Designated as safety issue: No ]
• Neurocognitive function from baseline to up to 5 years using the ALTE07C1 protocol [ Designated as safety issue: No ]

• Estimation of the PFS distribution of patients with NGGCT treated with IFR [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  Kaplan-Meier estimates will be provided.
• Estimation of the OS distribution of patients with NGGCT treated with IFR assessed [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  Kaplan-Meier estimates will be provided.
• Estimation of the PFS distribution of patients with localized germinoma patients and CSF serum hCGβ of 50 mIU/mL or less or CSF serum hCGβ greater than 50 mIU/mL and less than or equal to 100 mIU/mL [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  Kaplan-Meier estimates will be provided.
• Estimation of the OS distribution of patients with localized germinoma patients and CSF serum hCGβ of 50 mIU/mL or less or CSF serum hCGβ greater than 50 mIU/mL and less than or equal to 100 mIU/mL [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  Kaplan-Meier estimates will be provided.

• Estimation of the PFS distribution of patients with NGGCT treated with IFR assessed up to 5 years [ Designated as safety issue: No ]
• Estimation of the OS distribution of patients with NGGCT treated with IFR assessed up to 5 years [ Designated as safety issue: No ]
• Estimation of the PFS distribution of patients with localized germinoma patients and CSF serum hCGβ ≤ 50 mIU/mL or CSF serum hCGβ > 50 mIU/mL and ≤ 100 mIU/mL assessed up to 5 years [ Designated as safety issue: No ]
• Estimation of the OS distribution of patients with localized germinoma patients and CSF serum hCGβ ≤ 50 mIU/mL or CSF serum hCGβ > 50 mIU/mL and ≤ 100 mIU/mL assessed up to 5 years [ Designated as safety issue: No ]

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 or by stopping them from dividing. Radiation therapy uses high-energy x rays to kill tumor cells. Giving chemotherapy with radiation therapy may kill more tumor cells. This phase II trial studies how well chemotherapy and radiation therapy work in treating younger patients with newly diagnosed central nervous system germ cell tumors.

PRIMARY OBJECTIVES:

I. To determine, as measured by the 3-year progression-free survival (PFS) rate and patterns of failure, whether dose and volume of irradiation can be safely reduced to 30.6 Gy whole ventricular-field irradiation (WVI) plus 23.4 Gy primary site boost instead of 36 Gy craniospinal irradiation (CSI) plus primary site boost in the subgroup of children and young adults with localized nongerminomatous germ cell tumor (NGGCT) who have a magnetic resonance imaging (MRI) and tumor marker criteria (CSF and serum) for confirmed complete response (CR) or partial response (PR) to induction chemotherapy and negative serum and cerebrospinal fluid (CSF) tumor markers OR in patients who have less than a PR after induction chemotherapy with negative tumor markers who undergo a second-look surgery and are found to have only mature teratoma, residual scar or fibrosis, and fit the definition of CR/PR after second-look surgery.

II. To determine, as measured by the 3-year PFS rate and patterns of failure, whether simplified chemotherapy followed by dose-reduced radiation therapy is effective for treating children and young adults with localized primary central nervous system (CNS) germinoma who present with serum and/or CSF human chorionic gonadotropin-beta (hCGβ) =< 50 mIU/mL.

III. To prospectively evaluate and longitudinally model the cognitive, social, and behavioral functioning of children and young adults who are treated with reduced radiation dose and volume of irradiation in Stratum 1 (NGGCT) and with dose-reduced radiation therapy in Stratum 2 (Germinoma) using the ALTE07C1 protocol (This objective will be assessed independently for the two strata).

SECONDARY OBJECTIVES:

To estimate the PFS and overall survival (OS) distributions of patients with NGGCT treated with 30.6 Gy WVI and involved-field radiation therapy (IFR) focal boost to 54 Gy. II. To estimate the PFS and OS distributions of localized-germinoma patients who present with serum and/or CSF hCGβ ≤ 50 mIU/mL vs serum and/or CSF hCGβ > 50 mIU/mL and =< 100 mIU/mL.

OUTLINE: This is a multicenter study. Patients are stratified according to localized primary disease (nongerminomatous germ cell tumor [NGGCT] vs germinoma).

Stratum 1 (NGGCT): Patients receive induction therapy comprising carboplatin IV over 15-60 minutes on day 1 and etoposide IV over 1-2 hours on days 1-3 of courses 1, 3, and 5. Patients also receive ifosfamide IV over 1 hour and etoposide over 1-2 hours on days 1-5 of courses 2, 4, and 6. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients with responsive disease (complete [CR] or partial response [PR]) to induction chemotherapy undergo radiotherapy once daily (QD) 5 days a week for 6 weeks. Patients with PR, stable disease (SD), or progressive disease (PD) and normalization of tumor levels undergo second-look surgery. Patients who achieve CR or PR after second-look surgery undergo radiotherapy.

Stratum 2 (Germinoma): Patients receive induction therapy comprising carboplatin IV over 15-60 minutes on day 1 and etoposide IV over 1-2 hours on days 1-3. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with CR or continued CR undergo radiotherapy QD 5 days a week for approximately 4 weeks. Patients with PR, SD, or PD with normal tumor markers may undergo second-look surgery. Patients found to have mature teratoma or non-viable tumor during surgery undergo radiotherapy. Patients with PR or SD with residual disease (=< 1.5 cm) and suprasellar (> 0.5 cm) or pineal (> 1 cm) involvement and normal tumor markers undergo radiotherapy after chemotherapy without second-look surgery.

After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for 2 years, and then annually for up to 3 years.

• Childhood Central Nervous System Choriocarcinoma
• Childhood Central Nervous System Embryonal Tumor
• Childhood Central Nervous System Germ Cell Tumor
• Childhood Central Nervous System Germinoma
• Childhood Central Nervous System Mixed Germ Cell Tumor
• Childhood Central Nervous System Teratoma
• Childhood Central Nervous System Yolk Sac Tumor
• Childhood Pineal Parenchymal Tumor

• Procedure: therapeutic conventional surgery
  Undergo surgery
• Radiation: 3-dimensional conformal radiation therapy
  Undergo 3D-CRT
  Other Names:

  • 3D conformal radiation therapy
  • 3D-CRT
• Radiation: intensity-modulated radiation therapy
  Undergo IMRT
  Other Name: IMRT
• Drug: carboplatin
  Given IV
  Other Names:

  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
• Drug: etoposide
  Given IV
  Other Names:

  • EPEG
  • VP-16
  • VP-16-213
• Drug: ifosfamide
  Given IV
  Other Names:

  • Cyfos
  • Holoxan
  • IFF
  • IFX
  • IPP

Inclusion Criteria:

• Patients must be newly diagnosed with localized primary CNS non germinomatous germ cell tumor (NGGCT) (Stratum 1) or localized primary CNS germinoma (Stratum 2); germ cell tumors (GCTs) 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 hCGβ > 100 mIU/mL or any elevation of serum and 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 hCGβ 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 one of the following criteria:

    • Patients with institutional normal AFP AND hCGβ 5 to ≤ 50 mIU/mL in serum and/or CSF are eligible; no histologic confirmation required
    • Patients with bifocal (pineal + suprasellar) involvement or pineal lesion with diabetes insipidus AND hCGβ ≤ 100 mIU/mL and institutional normal AFP in serum and/or CSF are eligible; no histologic confirmation required
    • Patients with histologically confirmed germinoma or germinoma mixed with mature teratoma and hCGβ ≤ 100 mIU/mL and institutional normal AFP in serum and/or CSF are eligible
• Patients must have negative lumbar CSF cytology; lumbar CSF must be obtained unless medically contraindicated
• Patients must be enrolled on ALTE07C1 prior to enrollment on ACNS1123
• Patients with mature 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 either MRI evaluation or lumbar CSF cytology are not eligible
• Peripheral absolute neutrophil count (ANC) ≥ 1,000/μL
• Platelet count ≥ 100,000/μL (transfusion independent)
• Hemoglobin ≥ 8.0 g/dL (may receive red blood cell [RBC] transfusions)

• Creatinine clearance or radioisotope GFR ≥ 70 mL/min/1.73 m² OR serum creatinine based on age/gender as follows:

  • 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)
  • 1.5 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)
• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamic 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
• 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
• Patients who had more than 1 prior surgery/biopsy are eligible
• Patients must not have received any prior tumor-directed therapy other than surgical intervention and corticosteroids