High-Risk Neuroblastoma Chemotherapy Without G-CSF
Condition: Neuroblastoma
MeSH terms: Neuroblastoma
Study type: Interventional

Summary: 
      Patients will be asked to participate in this study because patients have been diagnosed with
      high-risk neuroblastoma, a common childhood cancer which has aggressive features. If left
      untreated, high-risk neuroblastoma is fatal. Children with high-risk neuroblastoma often
      respond to current available treatments, but there is a high risk that the cancer will
      return.

      This study will test the safety of giving standard induction treatment for high-risk
      neuroblastoma without one of the drugs commonly used to prevent side effects. Current
      treatment for high-risk neuroblastoma includes anti-cancer drugs (chemotherapy), surgery,
      radiation therapy and high-dose chemotherapy with hematopoietic stem cell rescue. Treatment
      takes about one year to complete and occurs in 3 phases: induction, consolidation, and
      maintenance. This study is limited to the induction phase of treatment.

      Induction therapy includes six chemotherapy drugs given in different combinations every 3
      weeks for a total of 6 courses. For the past decade, induction chemotherapy has been followed
      by a drug called granulocyte colony stimulating factor (G-CSF, filgrastim, peg-filgrastim,
      Neupogen, or Neulasta) to prevent side effects from the chemotherapy. G-CSF is routinely
      given to patients with high risk neuroblastoma after chemotherapy to stimulate white blood
      cell production and shorten the time period when the absolute neutrophil count (ANC), a type
      of white blood cell, is low after chemotherapy. G-CSF is known to shorten the period of low
      ANC by approximately 3 days. When the ANC is lowest, a patient is most at risk of getting a
      bacterial infection.

      Recent lab experiments in mice have shown that neuroblastoma tumor cells may respond to G-CSF
      by growing faster and metastasizing (spreading to other parts of the body). There have been
      no clinical trials comparing the survival of children with high risk neuroblastoma with or
      without G-CSF. This clinical trial is the first step towards giving induction chemotherapy
      with less G-CSF.

      The goal of this study is to determine if it is safe to give induction chemotherapy to
      children with neuroblastoma without giving G-CSF routinely.
    

Detailed description: 
      Chemotherapy:

      CYCLE 1+2: Topotecan and cyclophosphamide

      Cycle 3+5: Cisplatin and Etoposide

      Cycle 4+6: Vincristine, Cyclophosphamide and Doxorubicin

      Stem cell collection: After the third cycle of chemotherapy, stem cells will be collected for
      possible stem cell transplantation at a later date using apheresis. In order to have enough
      stem cells present in the blood, the patient will need to receive daily G-CSF injections
      before this collection.

      Surgery: After the 5th cycle of chemotherapy, most patients will have surgery to remove as
      much remaining tumor as possible.

      Growth factor support: Growth factors to increase the number of white blood cells, G-CSF and
      GM-CSF(granulocyte-macrophage colony stimulating factor) will not be given routinely in this
      study. GM-CSF will be given for patients who have serious bacterial infections or delays in
      administering chemotherapy because of low neutrophil counts. All people enrolled on the study
      will receive GM-CSF prior to having surgical removal of the main tumor. All people enrolled
      on the study will also receive G-CSF prior to having patients stem cells collected.

      Optional survey: This research study includes an optional survey regarding quality of life
      while on the study. This survey will be filled out after cycles 1 and 4 of chemotherapy.

      Drug Shortages:

      In the event of a drug shortage of a medication that is not a G-CSF or GM-CSF product, the
      provider may use best clinical judgment regarding omission of the agent or substitution with
      a different agent. The medical and research records of study patients should reflect that the
      patient was informed of any delays and/or modifications in protocol therapy related to the
      shortage of the agent and the associated risks.
    

Intervention name(s): Topotecan; Cyclophosphamide; Cisplatin; Etoposide; Vincristine; Cyclophosphamide; Doxorubicin; Sargramostim
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): CYCLE 1+2 (given by intravenous catheter daily for 5 days); CYCLE 1+2 (given by intravenous catheter daily for 5 days); Cycle 3+5 (given daily x 4 days); Cycle 3+5 (given daily for 3 days); Cycle 4+6 (given daily for 3 days); Cycle 4+6 (given daily for 2 days); Cycle 4+6 (given daily for 3 days); Granulocyte macrophage colony stimulating factor (rhu GM-CSF, rGM-CSF, GM-CSF)
Other intervention name(s): hycamtin; Cytoxan; CDDP; Platinol; Oncovin; Cytoxan; Adriamycin; GM-CSF
Intervention MeSH terms: Cyclophosphamide; Doxorubicin; Etoposide; Vincristine; Topotecan; Sargramostim
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Sargramostim; Cyclophosphamide; Topotecan; Cisplatin; Dexrazoxane; Doxorubicin; Etoposide; Filgrastim; Vincristine; Mesna