Neoadjuvant Chemotherapy With or Without Second-Look Surgery Followed by Radiation Therapy With or Without Peripheral Stem Cell Transplantation in Treating Patients With Intracranial Germ Cell Tumors
Condition: Brain Tumor; Central Nervous System Tumors; Childhood Germ Cell Tumor
MeSH terms: Neoplasms; Neoplasms, Germ Cell and Embryonal; Nervous System Neoplasms; Central Nervous System Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from
      dividing so they stop growing or die. Giving a chemotherapy drug before surgery may shrink
      the tumor so that it is no longer present by conventional imaging and tumor markers from
      serum and cerebrospinal fluid. Radiation therapy uses high-energy x-rays to damage tumor
      cells. Peripheral stem cell transplantation may allow the doctor to give higher doses of
      chemotherapy drugs and kill more tumor cells. Combining different types of therapy may kill
      more tumor cells.

      PURPOSE: This Phase II trial is studying how well neoadjuvant chemotherapy with or without
      surgery and with or without high dose chemotherapy and peripheral stem cell transplantation,
      can increase response rates prior to radiation therapy and increase progression free and
      overall surviving patients with newly diagnosed intracranial germ cell tumors.
    

Detailed description: 
      OBJECTIVES:

        -  Determine the response rate of patients with non-germinomatous germ cell tumors treated
           with neoadjuvant chemotherapy.

        -  Determine the progression-free survival and overall survival of patients treated with
           neoadjuvant chemotherapy with or without second-look surgery followed by radiotherapy
           with or without autologous peripheral blood stem cell transplantation (PBSCT).

        -  Determine whether additional complete responses can be achieved after high-dose thiotepa
           and etoposide with PBSCT in patients with persistently positive markers, histological
           evidence of residual malignant elements, or unresectable residual tumors after initial
           neoadjuvant chemotherapy.

        -  Determine patterns of recurrence in patients treated with this regimen.

        -  Correlate tumor marker response with radiographic and clinical measures of response, as
           well as findings at second-look surgery in patients with radiological evidence of
           residual disease.

      OUTLINE:

        -  Induction chemotherapy:

             -  Courses 1, 3, and 5: Patients receive carboplatin IV over 1 hour on day 1 and
                etoposide IV over 1 hour on days 1-3. Beginning on day 4, patients receive
                filgrastim (G-CSF) IV or subcutaneously (SC) for 10 days or until blood counts
                recover. Courses are 3 weeks in duration.

             -  Courses 2, 4, and 6: Patients receive etoposide IV over 1 hour followed by
                ifosfamide IV over 1 hour on days 1-5. Beginning on day 6, patients receive G-CSF
                IV or SC for 10 days or until blood counts recover. Courses are 3 weeks in
                duration.

      Patients undergo re-evaluation. Patients with a complete response (CR) go directly to
      radiotherapy. Approximately 3 weeks after completion of induction chemotherapy, all patients
      with less than a CR are encouraged to undergo second-look surgery.

      After second-look surgery, patients with a CR or a partial response (PR) go directly to
      radiotherapy. Patients with less than a PR undergo consolidation chemotherapy with peripheral
      blood stem cell rescue (PBSC) followed by radiotherapy.

        -  Consolidation chemotherapy: Patients undergo PBSC collection. Patients receive G-CSF SC
           until PBSC collection is complete. Patients then receive thiotepa IV over 3 hours
           followed by etoposide IV over 3 hours on days -5 to -3. PBSCs are reinfused on day 0.
           Beginning on day 1 and continuing until blood counts recover, patients receive G-CSF SC
           daily.

        -  Radiotherapy: All patients receive radiotherapy once daily 5 days a week for 5-6 weeks
           beginning after recovery from induction chemotherapy or second-look surgery or within 9
           weeks after PBSC reinfusion.

      Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months
      for 1 year, and then annually thereafter.

      PROJECTED ACCRUAL: A total of 80-100 patients will be accrued for this study within 36-42
      months.
    

Intervention name(s): carboplatin; etoposide; ifosfamide; thiotepa; adjuvant therapy; conventional surgery; neoadjuvant therapy; peripheral blood stem cell transplantation; radiation therapy
Intervention type(s): Drug; Drug; Drug; Drug; Procedure; Procedure; Procedure; Procedure; Radiation
Intervention description(s): Given IV; Given IV; Given IV; Given IV; craniospinal irradiation
Other intervention name(s): Paraplatin; NSC #241240; VP-16; VePesid; Etopophos; NSC #141540; Isophosphamide; Iphosphamide; Z4942; Ifex; NSC #109724; Tespa; Thiophosphamide; Triethylenethiophosphoramide Tspa; WR-45312; NSC #6396; Craniospinal irradiation (CSI) followed by boost radiation to the sites of gross disease at diagnosis.
Intervention MeSH terms: Carboplatin; Etoposide; Ifosfamide; Isophosphamide mustard; Thiotepa
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: childhood central nervous system germ cell tumor; childhood teratoma; recurrent childhood malignant germ cell tumor; childhood central nervous system choriocarcinoma; childhood central nervous system embryonal 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; recurrent childhood central nervous system embryonal tumor