Clinical Trial: 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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase II Study To Assess The Ability Of Neoadjuvant Chemotherapy Plus/Minus Second Look Surgery To Eliminate All Measurable Disease Prior To Radiotherapy For NGGCT

Brief 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 Summary:

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
    Sponsor: Children's Oncology Group
    

    Current Primary Outcome: Response to Induction Chemotherapy [ Time Frame: 18 weeks ]

    A patient who achieves a complete or partial response, defined a reduction of at least 65% in tumor size without complete disappearance of tumor after induction chemotherapy will be considered to have experienced response.
    
    
    

    Original Primary Outcome:
    
    

    Current Secondary Outcome:

    • Event-free Survival [ Time Frame: From time from study entry to death from any cause, disease progression or recurrence, or second malignant neoplasm. ]
    • Progression-free Survival [ Time Frame: From the time of the first progressive, non-metastatic event until the subsequent occurrence of relapse or progressive disease ]
      From study entry to disease progression or recurrence. Deaths that are clearly unrelated to disease progression, and second neoplasms, are censored in this analysis.
    • Overall Survival [ Time Frame: Time from study entry to death from any cause ]
    • Toxic Death [ Time Frame: 18 weeks ]
      Defined as death predominantly attributable to treatment-related causes.
    • Occurrence of Nonhematological Grade 4 Toxicity [ Time Frame: 18 weeks ]
    
    
    

    Original Secondary Outcome:
    
    Information By: Children's Oncology Group
    

    Dates:
    Date Received: October 3, 2002
    Date Started: January 2004
    Date Completion:
    Last Updated: February 7, 2017
    Last Verified: February 2017