Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Infants With Malignant Brain or Spinal Cord Tumors

Overview

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctors to give higher doses of chemotherapy drugs and kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy plus peripheral stem cell transplantation in treating infants with malignant brain or spinal cord tumors.

Full Title of Study: “A Pilot Study of Intensive Chemotherapy With Peripheral Stem Cell Support for Infants With Malignant Brain Tumors”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: December 2007

Detailed Description

OBJECTIVES: – Determine the maximum tolerated dose of thiotepa in infants with malignant brain or spinal cord tumors receiving intensive chemotherapy. – Determine the feasibility and toxicity of intensive chemotherapy with peripheral blood stem cell (PBSC) rescue in these patients. – Assess the feasibility of harvesting PBSCs in these patients. – Determine the complete response rate and overall event-free survival rate in patients treated with this regimen. OUTLINE: This is a pilot, multicenter study. Patients undergo surgery for diagnosis and maximal tumor resection. Within 6 weeks of surgery or when stable, patients begin induction chemotherapy comprising cisplatin IV over 6 hours on day 0; vincristine IV on days 0, 7, and 14; cyclophosphamide IV over 1 hour on days 1-2; and etoposide IV over 1 hour on days 0-2. Twenty four hours after the last cyclophosphamide dose, patients receive filgrastim (G-CSF) subcutaneously (SC) and undergo peripheral blood stem cell harvest 2 days later. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Within 6 weeks after induction chemotherapy, patients receive consolidation chemotherapy comprising carboplatin IV over 2 hours on days 0-1 followed immediately by escalating doses of thiotepa IV over 2 hours. Patients then undergo peripheral blood stem cell transplantation 48 hours after the last thiotepa dose. Patients receive G-CSF SC daily on days 3 to 21. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients experiencing dose-limiting toxicity due to thiotepa are removed from the study. Patients are followed at 4 weeks, every 3 months for 1 year, every 6 months for 3 years, and then annually for 3 years or until relapse. PROJECTED ACCRUAL: A total of 83 patients will be accrued for this study within 1 year.

Interventions

  • Biological: filgrastim
    • Given IV
  • Drug: carboplatin
    • Given IV
  • Drug: cisplatin
    • Given IV
  • Drug: cyclophosphamide
    • Given IV
  • Drug: etoposide
    • Given IV
  • Drug: thiotepa
    • Given IV
  • Drug: vincristine sulfate
    • Given IV
  • Procedure: conventional surgery
  • Procedure: peripheral blood stem cell transplantation

Arms, Groups and Cohorts

  • Experimental: Treatment (combination chemotherapy, PBSC transplant)
    • Pts undergo conventional surgery for diagnosis & max tumor resection. In 6 wks of surgery or when stable pts begin induction chemotherapy(cisplatin IV over 6 hrs on day 0; vincristine sulfate IV on days 0,7,14; cyclophosphamide IV over 1 hr on days 1-2; and etoposide IV over 1 hr on days 0-2. 24 hrs after the last cyclophosphamide dose, pts receive filgrastim (G-CSF) & undergo peripheral blood stem cell harvest 2 days later. Treatment repeats every 21 days for up to 3 crs. Within 6 wks after induction, pts receive consolidation (carboplatin IV over 2 hrs on days 0-1 next esc. doses of thiotepa IV over 2 hrs. Pts undergo peripheral blood stem cell transplantation 48 hrs after last thiotepa dose. Pts receive G-CSF SC daily on days 3-21. Treatment repeats every 21 days for up to 3 crs. Pts with dose-limiting toxicity due to thiotepa are removed from study. Pts are followed at 4 wks, 3 mths for 1 yr, 6 mths for 3 yrs, annually for 3 yrs or until relapse.

Clinical Trial Outcome Measures

Primary Measures

  • Feasibility
    • Time Frame: Up to 4 weeks after completion of study treatment
    • Demonstrate the feasibility of administering this regimen, to select an acceptable Thiotepa dose for Consolidation therapy, and to document significant toxicities and estimate their overall rates
  • Maximal tolerated dose of thiotepa for consolidation therapy
    • Time Frame: 9 weeks
    • The dose level will be assigned within 3 working days prior to beginning Consolidation.
  • Overall rates of significant toxicities including grade IV ototoxicity, electrolytic wasting (grade IV), and hemorrhagic cystitis (grade IV)
    • Time Frame: Up to 6 years
    • Estimates will be obtained using life-table methods with an event defined as the first occurrence of toxicity. Graded using the CCG Toxicity and Complications Criteria.

Secondary Measures

  • Event Free Survival
    • Time Frame: From the time of study entry to the first occurrence of death by any cause, progression or recurrence of disease or occurrence of a second malignant neoplasm, assessed up

Participating in This Clinical Trial

DISEASE CHARACTERISTICS:

  • Histologically proven malignant brain or spinal cord tumor, including the following: – Primitive neuroectodermal tumor – Ganglioneuroblastoma – Medulloblastoma neuroblastoma – Desmoplastic medulloblastoma – Medulloepithelioma – Ependymoma neuroepithelioma – Anaplastic ependymoma germ cell tumor – Astrocytoma germinoma – Anaplastic astrocytoma – Embryonal carcinoma – Glioblastoma endodermal sinus tumor – Gliosarcoma malignant teratoma – Choroid plexus carcinoma – Mixed germ cell tumor – Cerebellar sarcoma – Pineoblastoma – Atypical teratoid/rhabdoid tumor – Choriocarcinoma – Teratoma (malignant or with malignant transformations) – Diffusely involved brain stem tumors allowed if there is evidence of brain stem glioma by CT scan or MRI PATIENT CHARACTERISTICS: Age: – 6 months to less than 3 years Performance Status: – Not specified Life Expectancy: – More than 8 weeks Hematopoietic: – Absolute neutrophil count greater than 1,000/mm^3 – Platelet count greater than 100,000/mm^3 Hepatic: – Bilirubin less than 2.0 mg/dL Renal: – Glomerular filtration rate or creatinine clearance greater than 70 mL/min PRIOR CONCURRENT THERAPY: Biologic therapy: – No prior biologic therapy Chemotherapy: – No prior chemotherapy Endocrine therapy: – Prior corticosteroids allowed Radiotherapy: – No prior radiotherapy Surgery: – No more than 6 weeks since prior surgery – Recovered from prior surgery (stable)

Gender Eligibility: All

Minimum Age: N/A

Maximum Age: 2 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Children’s Oncology Group
  • Collaborator
    • National Cancer Institute (NCI)
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Bruce H. Cohen, MD, Study Chair, The Cleveland Clinic

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