Combination Chemotherapy Plus Peripheral Stem Cell Transplantation Followed by Surgery and/or Radiation Therapy in Treating Young Patients With Advanced Neuroblastoma
Condition: Neuroblastoma
MeSH terms: Neuroblastoma
Study type: Interventional
Phase: Phase 1

Summary: 
      RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so
      they stop growing or die. Peripheral stem cell transplantation may allow doctors to give
      higher doses of chemotherapy drugs and kill more tumor cells. Radiation therapy uses
      high-energy x-rays to damage tumor cells.

      PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy plus peripheral
      stem cell transplantation followed by surgery and/or radiation therapy in treating young
      patients who have newly diagnosed advanced neuroblastoma.
    

Detailed description: 
      OBJECTIVES: I. Estimate the maximum tolerated dose of carboplatin that can be given in
      combination with cyclophosphamide (CTX) and etoposide following high dose CTX, doxorubicin,
      and vincristine in patients with newly diagnosed stage IV neuroblastoma. II. Determine the
      hematologic and nonhematologic toxic effects of this regimen in this patient population. III.
      Determine the change in neuroblastoma tumor cell content in peripheral blood stem cells
      (PBSC) collected following chemotherapy. IV. Assess the feasibility of repetitive collection,
      storage, and infusion of PBSC with multicycle high-dose chemotherapy in pediatric patients.
      V. Assess hematopoietic recovery following PBSC infusion as well as the CD34 content and
      CFU-GM yield of the PBSC products. VI. Assess the response rate and disease-free survival in
      the context of a phase I pilot study. VII. Determine the feasibility of administering
      twice-daily radiotherapy fractions to post-chemotherapy residual tumor volumes in
      neuroblastoma patients.

      OUTLINE: This is a dose escalation study of carboplatin. Patients receive induction
      chemotherapy consisting of vincristine IV over 24 hours, cyclophosphamide IV over 4 hours,
      and doxorubicin IV over 24 hours on days 0, 1, 21, and 22. Patients receive filgrastim
      (G-CSF) subcutaneously (SQ) or IV beginning on days 3 and 24 and continuing until blood
      counts recover. Patients undergo peripheral blood stem cell (PBSC) collection after course 2
      of induction chemotherapy. Patients receive G-CSF SQ or IV for 2 days prior to and during
      collection. PBSC are collected daily for 1-3 days. Patients may undergo autologous bone
      marrow collection after course 1 of consolidation therapy (after PBSC collection). Following
      mobilization, patients receive consolidation chemotherapy consisting of etoposide IV over 4
      hours on days 0, 1, and 2 and carboplatin IV over 1 hour and cyclophosphamide IV over 4 hours
      on days 0 and 1. Patients receive G-CSF SQ or IV beginning on day 3 (within 4 hours of PBSC
      infusion) and continuing until blood counts recover. Patients receive PBSC reinfusion at
      48-72 hours following completion of each chemotherapy course. Treatment repeats every 3 weeks
      for 3 courses in the absence of disease progression or unacceptable toxicity. Upon recovery
      from consolidation chemotherapy, patients with no disease progression undergo tumor resection
      with or without radiotherapy. Patients undergoing radiotherapy receive therapy twice daily
      over 7 days. Patients with no disease progression, less than 2% detectable bone marrow
      disease, and adequate bone marrow cellularity may undergo additional therapy consisting of
      autologous bone marrow transplantation per appropriate transplant protocol. Cohorts of 6-12
      patients receive escalating doses of carboplatin until the maximum tolerated dose (MTD) is
      determined. The MTD is defined as the dose preceding that at which 3 of 6 or 4 of 12 patients
      experience dose limiting toxicity. Patients are followed every 3 months for 2 years, every 6
      months for 3 years, and then annually thereafter.

      PROJECTED ACCRUAL: A total of 24-30 patients will be accrued for this study within
      approximately 2 years.
    

Intervention name(s): filgrastim; carboplatin; cyclophosphamide; doxorubicin hydrochloride; etoposide; mesna; vincristine sulfate; conventional surgery; peripheral blood stem cell transplantation; low-LET cobalt-60 gamma ray therapy; low-LET photon therapy
Intervention type(s): Biological; Drug; Drug; Drug; Drug; Drug; Drug; Procedure; Procedure; Radiation; Radiation
Other intervention name(s): G-CSF (Granulocyte colony stimulating factor; Neupogen; NSC# 614629; CBDCA; Cis-diamine [1,1-cyclobutane-dicarboxylato] platinum); NSC# 241240; Cytoxan; CTX; NSC# 26271; Adriamycin; NSC #123127; VP-16; NSC# 141540; Sodium 2-mercaptoethane sulfonate; NSC# 113891; Oncovin; VCR; Leucocristine; NSC# 67474
Intervention MeSH terms: Cobalt; Cyclophosphamide; Carboplatin; Doxorubicin; Liposomal doxorubicin; Etoposide; Vincristine; Lenograstim; Mesna
Primary purpose: Treatment
Keywords: disseminated neuroblastoma