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A Study of High Risk Induction Chemotherapy for Neuroblastoma Without Prophylactic Administration of Myeloid Growth Factors

NCT02786719

Description:

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.

Related Conditions:
  • Neuroblastoma
Recruiting Status:

Active, not recruiting

Phase:

N/A

Trial Eligibility

Document

A Study of High Risk Induction <span class="go-doc-concept go-doc-intervention">Chemotherapy</span> for <span class="go-doc-concept go-doc-disease">Neuroblastoma</span> Without Prophylactic Administration of Myeloid Growth Factors

Title

  • Brief Title: A Study of High Risk Induction Chemotherapy for Neuroblastoma Without Prophylactic Administration of Myeloid Growth Factors
  • Official Title: A Safety Pilot Study of High Risk Induction Chemotherapy for Neuroblastoma Without Prophylactic Administration of Myeloid Growth Factors
  • Clinical Trial IDs

    NCT ID: NCT02786719

    ORG ID: H-38179 (SPRING)

    NCI ID: SPRING

    Trial Conditions

    Neuroblastoma

    Trial Interventions

    Drug Synonyms Arms
    Topotecan Neuroblastoma treatment without G-CSF
    Cyclophosphamide Neuroblastoma treatment without G-CSF
    Cisplatin Neuroblastoma treatment without G-CSF
    Etoposide Neuroblastoma treatment without G-CSF
    Vincristine Neuroblastoma treatment without G-CSF
    Cyclophosphamide Neuroblastoma treatment without G-CSF
    Doxorubicin Neuroblastoma treatment without G-CSF
    Sargramostim Neuroblastoma treatment without G-CSF

    Trial Purpose

    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.

    Trial Arms

    Name Type Description Interventions
    Neuroblastoma treatment without G-CSF Experimental Induction chemotherapy only, including 6 cycles of chemotherapy, tumor resection, and stem cell collection Topotecan, Cyclophosphamide, Cisplatin, Etoposide, Vincristine, Cyclophosphamide, Doxorubicin, Sargramostim

    Eligibility Criteria

    Inclusion Criteria:

    - Age greater than 12 months and less than 18 years old at diagnosis

    - Newly diagnosed neuroblastoma or ganglioneuroblastoma as verified by histology and/or
    demonstration of tumor cells in bone marrow with elevated urinary catecholamine
    metabolites

    - Must meet criteria for High Risk disease

    - Patients with International Neuroblastoma Staging System (INSS) stage 4 disease
    are eligible with the following: MYCN gene amplification (greater than four-fold
    increase in MYCN signals as compared to reference signals), regardless of age or
    additional biologic features, Age greater than 18 months ( greater than 547
    days) regardless of biologic features, Age 12 -18 months (365 - 547 days) with
    any of the following unfavorable biologic features (unfavorable pathology and/or
    DNA index = 1) or any biologic feature that is
    indeterminate/unsatisfactory/unknown

    - Patients with INSS stage 3 disease are eligible with the following: MYCN
    amplification, regardless of age or additional biologic features, Age greater
    than 18 months ( greater than 547 days) with unfavorable pathology, regardless
    of MYCN status

    - Patients with INSS stage 2a/2b with MYCN amplification regardless of age or
    additional biologic features

    - Patients greater than or equal to 365 days initially diagnosed with INSS stage 1
    or 2 who progressed to a stage 4 without interval chemotherapy

    - Patients may have had no prior systemic therapy except: Localized emergency radiation
    to sites of life threatening or functioning disease, No more than 1 cycle of
    chemotherapy according to low or intermediate risk regimens prior to determination of
    MYCN amplification and histology, as long as the patient DID NOT receive any type of
    granulocyte colony stimulating factor (G-CSF) as part of that therapy.

    - Patients must have adequate hematopoietic function defined as: Absolute neutrophil
    count (ANC) greater than or equal to 750/L, Platelet count greater than or equal to
    75,000/L, The above criteria do not have to be met if the patient has bone marrow
    involvement of tumor.

    - Patients must have adequate liver function defined as: Direct bilirubin less than or
    equal to 1.5 mg/dL or total bilirubin 1.5 mg/dL, aspartate aminotrasnferase (AST)
    and alanine aminotransferase (ALT) less than or equal to10 x upper limit of normal
    for age

    - Patients must have adequate renal function as defined as: Creatinine clearance (CrCl)
    or radioisotope glomerular filtration rate (GFR) greater than or equal to 70
    mL/min/.73 m2 OR A serum creatinine based on age/gender.

    - Patients must have adequate cardiac function as defined as: Shortening fraction of
    greater than or equal to 27 % by echocardiogram, or Ejection fraction of greater than
    or equal to 50 % by radionuclide angiogram

    Exclusion Criteria:

    - Patients who do not meet inclusion criteria

    - Patients who are pregnant or lactating

    - Patients who have received G-CSF since the time of diagnosis of the current disease

    Minimum Eligible Age: 12 Months

    Maximum Eligible Age: 18 Years

    Eligible Gender: Both

    Primary Outcome Measures

    the incidence of infections in chemotherapy cycles NOT followed by hematopoietic growth factors

    Secondary Outcome Measures

    incidence of delay in chemotherapy administration due to prolonged neutrophil recovery

    the number of antibiotic days and hospital days due to fever and/or infection

    number of platelet transfusions in in patients undergoing induction chemotherapy

    the response rate following induction chemotherapy without prophylactic granulocyte colony stimulating factor (G-CSF)

    Trial Keywords

    Sargramostim

    Cyclophosphamide

    Topotecan

    Cisplatin

    Dexrazoxane

    Doxorubicin

    Etoposide

    Filgrastim

    Vincristine

    Mesna