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
Study type: Interventional
Phase: Phase 3

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.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Compare event-free survival and overall survival of patients with newly diagnosed
           primary CNS germ cell tumor treated with conventional radiotherapy alone (regimen A) vs
           chemotherapy followed by tumor response-based radiotherapy (regimen B).

      Secondary

        -  Determine the complete response rate in patients treated with regimen B.

        -  Determine the acute and subacute toxicity of regimen B in these patients.

        -  Compare treatment-related morbidity, in terms of verbal learning and memory, executive
           functioning, and quality of life, in patients treated with these regimens.

        -  Determine the prognostic value of baseline serum, lumbar, and intraventricular levels of
           human chorionic gonadotropin levels from patients treated with these regimens.

        -  Determine the prognostic value of extent of disease (M+ vs modified M+ vs M0) on
           event-free survival and overall survival of patients treated with these regimens.

      OUTLINE: This is a randomized, multicenter study. Patients are stratified according to tumor
      location (pineal vs suprasellar vs pineal + suprasellar or other), and disease stage
      (disseminated vs occult multi-focal vs localized). Patients are randomized to 1 of 2
      treatment regimens.

      All patients undergo an operative procedure (endoscopic biopsy, stereotactic biopsy, or open
      craniotomy) to confirm the diagnosis of pure germ cell germinoma followed by an
      intraoperative and perioperative staging evaluation.

        -  Regimen A (radiotherapy only): Within 52 days of surgery, patients undergo standard-dose
           radiotherapy once daily on days 1-5 for approximately 5-6 weeks.

        -  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.

      Patients achieving a complete response (CR) proceed to reduced-dose radiotherapy. Patients
      with minimal residual disease (MRD), a partial response (PR), or stable disease (SD) receive
      chemotherapy courses 3 and 4 as outlined below. Patients with progressive disease undergo a
      second surgical procedure for biopsy and are restaged. Patients with a confirmed diagnosis of
      germ cell tumor with no change in tumor markers and no new lesions after restaging proceed to
      chemotherapy courses 3 and 4.

        -  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) subcutaneously 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 are restaged. Patients with a confirmed diagnosis of germ cell tumor
      after restaging undergo standard radiotherapy as in regimen A.

        -  Reduced-dose radiotherapy: Within 6 weeks of starting course 4, patients undergo
           lower-dose radiotherapy once daily on days 1-5 for 5 weeks.

      Treatment in both regimens continues in the absence of unacceptable toxicity or in the event
      that a non-germinomatous germ cell tumor is detected.

      Quality of life and neuropsychological function within the domains of intelligence,
      attention-concentration, memory, and executive functioning are assessed at 9, 30, and 60
      months after diagnosis.

      Patients are followed every 4 months for 2 years, and then annually thereafter.

      PROJECTED ACCRUAL: A total of 225 patients (approximately 112 per treatment regimen) will be
      accrued for this study within 5 years.
    

Intervention name(s): filgrastim; carboplatin; cisplatin; cyclophosphamide; etoposide; radiation therapy
Intervention type(s): Biological; Drug; Drug; Drug; Drug; Radiation
Intervention description(s): 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
Other intervention name(s): Granulocyte Colony-Stimulating Factor; r-metHuG-CSF; G-CSF; Neupogen; NSC #61462; Paraplatin; NSC #241240; Cis-diamminedichloroplatinum II; Platinol-AQ; NSC #119875; Cytoxan; NSC #26271; VePesid; Etopophos; VP-16; NSC #141540
Intervention MeSH terms: Cyclophosphamide; Cisplatin; Carboplatin; Etoposide; Lenograstim
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: childhood central nervous system germ cell tumor