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NCT00003093 · CITED IN SOURCE DOCUMENTS

Combination Chemotherapy in Treating Children With Neuroblastoma

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE3
Status at capture
COMPLETED
Registry last update
2014-08-01

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. Combination chemotherapy plus surgery may be an effective treatment for neuroblastoma. PURPOSE: This phase III trial is studying how well combination chemotherapy followed by surgery works in treating young patients with neuroblastoma.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

No posted result sections were captured. Registered plans do not establish that a treatment works.

Who could take part
eligibility Criteria
DISEASE CHARACTERISTICS: * Histologically proven neuroblastoma or maturing ganglioneuroma that is judged to be intermediate risk by one of the following criteria: * International Neuroblastoma Staging System (INSS) stage III * Under 1 year old, MYCN oncogene nonamplified, and any ploidy * 1 to 20 years old, MYCN nonamplified, favorable Shimada histology * INSS stage IV * Under 1 year old, MYCN nonamplified, any ploidy * INSS stage IVS * Under 1 year old, MYCN nonamplified, unfavorable Shimada histology and any ploidy OR favorable Shimada histology and diploidy * All patients must be registered on the companion neuroblastoma biology study (COG-ANBL00B1) PATIENT CHARACTERISTICS: Age: * Under 21 Performance status: * Not specified Life expectancy: * Not specified Hematopoietic: * Not specified Hepatic: * Not specified Renal: * Not specified Other: * No abnormal organ function that would prohibit chemotherapy unless due to neuroblastoma PRIOR CONCURRENT THERAPY: Biologic therapy: * Not specified Chemotherapy: * Prior chemotherapy for patients with intradural extension and emergent paresis allowed provided biopsy was performed within 96 hours after treatment Endocrine therapy: * Not specified Radiotherapy: * Not specified Surgery: * Not specified Other: * No other prior therapy
healthy Volunteers
false
maximum Age
20 Years
sex
ALL
std Ages
  1. CHILD
  2. ADULT
Treatment arms and interventions
arm Groups
  1. description
    See detailed description.
    intervention Names
    1. Biological: filgrastim
    2. Biological: sargramostim
    3. Drug: carboplatin
    4. Drug: cyclophosphamide
    5. Drug: doxorubicin hydrochloride
    6. Drug: etoposide
    7. Procedure: conventional surgery
    8. Procedure: neoadjuvant therapy
    label
    Treatment
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Treatment
    name
    filgrastim
    other Names
    1. Granulocyte Colony-Stimulating Factor
    2. r-metHuG-CSF
    3. G-CSF
    4. Neupogen®
    5. NSC #614629
    type
    BIOLOGICAL
  2. arm Group Labels
    1. Treatment
    name
    sargramostim
    other Names
    1. Granulocyte Macrophage-Colony Stimulating Factor
    2. rhu GM-CSF
    3. GM-CSF
    4. Prokine
    5. Leukine
    6. NSC #613795
    type
    BIOLOGICAL
  3. arm Group Labels
    1. Treatment
    name
    carboplatin
    other Names
    1. Paraplatin
    2. NSC-241240
    type
    DRUG
  4. arm Group Labels
    1. Treatment
    name
    cyclophosphamide
    other Names
    1. Cytoxan
    2. NSC-26271
    type
    DRUG
  5. arm Group Labels
    1. Treatment
    name
    doxorubicin hydrochloride
    other Names
    1. Adriamycin
    2. NSC-123127
    type
    DRUG
  6. arm Group Labels
    1. Treatment
    name
    etoposide
    other Names
    1. VP-16
    2. VePesid
    3. NSC-141540
    type
    DRUG
  7. arm Group Labels
    1. Treatment
    name
    conventional surgery
    type
    PROCEDURE
  8. arm Group Labels
    1. Treatment
    name
    neoadjuvant therapy
    type
    PROCEDURE
Study design
allocation
NA
intervention Model
SINGLE_GROUP
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
573
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. measure
    Event Free Survival
Full study description
brief Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. Combination chemotherapy plus surgery may be an effective treatment for neuroblastoma. PURPOSE: This phase III trial is studying how well combination chemotherapy followed by surgery works in treating young patients with neuroblastoma.
detailed Description
OBJECTIVES: * Determine whether the use of selected prognostic variables to assign treatment increases the event-free survival and overall survival in children with intermediate-risk neuroblastoma. * Determine the acute and long-term morbidity and toxicity of surgery and combination chemotherapy in this patient population. * Assess the relationship between extent of tumor resection and event-free and overall survival in patients treated with this regimen. OUTLINE: Patients receive carboplatin IV over 1 hour on days 0, 21, and 63; cyclophosphamide IV over 1 hour on days 21 and 42; doxorubicin IV over 15-60 minutes on days 21 and 63; and etoposide IV over 2 hours on days 0-2, 42-44, and 63-65. Patients under 60 days of age also receive filgrastim (G-CSF) or sargramostim (GM-CSF) subcutaneously beginning 24 hours after the last chemotherapy administration and continuing until blood counts recover. Patients with favorable biology who do not achieve complete remission then undergo surgery to remove or debulk residual disease on day 84 or when blood counts recover. Patients with favorable biology who achieve partial response and surgery to the primary site is not deemed in the best interest of the patient may receive additional chemotherapy (as below) and delay surgery to the primary site after completion of chemotherapy. Patients with unfavorable biology receive additional chemotherapy comprising cyclophosphamide IV over 1 hour on days 84, 105, and 147; etoposide IV over 2 hours on days 84-86 and 126-128; carboplatin IV over 1 hour on days 105 and 126; and doxorubicin IV over 15-60 minutes on days 105 and 147. Patients then undergo debulking surgery on day 168 or when blood counts recover. Some patients may then undergo radiotherapy after surgery. Patients are followed monthly for 6 months, every 2 months for 6 months, every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter. PROJECTED ACCRUAL: A total of 400 patients will be accrued for this study.
Source references
references
  1. citation
    Dubois SG, Geier E, Batra V, Yee SW, Neuhaus J, Segal M, Martinez D, Pawel B, Yanik G, Naranjo A, London WB, Kreissman S, Baker D, Attiyeh E, Hogarty MD, Maris JM, Giacomini K, Matthay KK. Evaluation of Norepinephrine Transporter Expression and Metaiodobenzylguanidine Avidity in Neuroblastoma: A Report from the Children's Oncology Group. Int J Mol Imaging. 2012;2012:250834. doi: 10.1155/2012/250834. Epub 2012 Sep 25.
    pmid
    23050139
    type
    BACKGROUND
  2. citation
    Marachelian A, Shimada H, Sano H, Jackson H, Stein J, Sposto R, Matthay KK, Baker D, Villablanca JG. The significance of serial histopathology in a residual mass for outcome of intermediate risk stage 3 neuroblastoma. Pediatr Blood Cancer. 2012 May;58(5):675-81. doi: 10.1002/pbc.23250.
    pmid
    22493777
    type
    BACKGROUND
  3. citation
    Meany HJ, Attiyeh EF, Naranjo A, et al.: Outcome analysis of non-high-risk neuroblastoma patients enrolled on Children's Oncology Group trials P9641 and A3961. [Abstract] J Clin Oncol 30 (Suppl 15): A-9533, 2012.
    type
    BACKGROUND
  4. citation
    Attiyeh EF, Mosse YP, Diskin S, et al.: Identification of genomic DNA signatures predicting relapse in low- and intermediate- risk neuroblastoma using a case control design and high-density SNP genotyping: a Children's Oncology Group (COG) study. [Abstract] J Clin Oncol 25 (Suppl 18): A-9500, 526s, 2007.
    type
    BACKGROUND
  5. citation
    Baker DL, Schmidt ML, Cohn SL, Maris JM, London WB, Buxton A, Stram D, Castleberry RP, Shimada H, Sandler A, Shamberger RC, Look AT, Reynolds CP, Seeger RC, Matthay KK; Children's Oncology Group. Outcome after reduced chemotherapy for intermediate-risk neuroblastoma. N Engl J Med. 2010 Sep 30;363(14):1313-23. doi: 10.1056/NEJMoa1001527.
    pmid
    20879880
    type
    RESULT
  6. citation
    Baker DL, Schmidt M, Cohn S, et al.: A phase III trial of biologically-based therapy reduction for intermediate risk neuroblastoma. [Abstract] J Clin Oncol 25 (Suppl 18): A-9504, 2007.
    type
    RESULT
Source notices and limitations
    Discovery and provenance
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        90% (&#177; 4%) for children aged 18 months and older.[<a href="#cit/section_1.79">79</a>]</li><li>In the COG intermediate-risk study <a href="/clinicaltrials/NCT00003093">A3961 (NCT00003093)</a> that included only <em class="gene-name">MYCN</em>-nonamplified tumors, infants with INSS stage 3 tumors were compared with children w
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        children aged 18 months and older.[<a href="#cit/section_1.79">79</a>]</li><li>In the COG intermediate-risk study <a href="/clinicaltrials/NCT00003093">A3961 (NCT00003093)</a> that included only <em class="gene-name">MYCN</em>-nonamplified tumors, infants with INSS stage 3 tumors were compared with children with INSS stage 3 fa
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        mes for many subsets of intermediate-risk children who were treated with substantially reduced chemotherapy, compared with the earlier <a href="/clinicaltrials/NCT00003093">COG-A3961 (NCT00003093)</a> study.[<a href="#cit/section_1.102">102</a>]</p> </section> </section><h6 do-not-show="toc">References</h6><ol><li id="s
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        intermediate-risk children who were treated with substantially reduced chemotherapy, compared with the earlier <a href="/clinicaltrials/NCT00003093">COG-A3961 (NCT00003093)</a> study.[<a href="#cit/section_1.102">102</a>]</p> </section> </section><h6 do-not-show="toc">References</h6><ol><li id="section_1.1">Childhood ca
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        biology who were aged 12 to 18 months.[<a href="#cit/section_7.9">9</a>]<div class="pdq-content-list"><ul id="_647"><li>In the legacy (<a href="/clinicaltrials/NCT00003093">A3961 [NCT00003093]</a>) study, the administration of neoadjuvant chemotherapy facilitated at least a partial resection of 99.6% of previously unresectable t
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        d 12 to 18 months.[<a href="#cit/section_7.9">9</a>]<div class="pdq-content-list"><ul id="_647"><li>In the legacy (<a href="/clinicaltrials/NCT00003093">A3961 [NCT00003093]</a>) study, the administration of neoadjuvant chemotherapy facilitated at least a partial resection of 99.6% of previously unresectable tumors. No significan
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        nt is kept low to minimize long-term effects, as used in previous COG trials (<a href="/clinicaltrials/NCT00003119">COG-P9641</a> and <a href="/clinicaltrials/NCT00003093">COG-A3961</a>).[<a href="#cit/section_10.16">16</a>,<a href="#cit/section_10.17">17</a>,<a href="#cit/section_10.19">19</a>] </p> <p id="_801" tabind
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      8. context exact
        be treated according to tumor biology, as defined in the previous COG trials (<a href="/clinicaltrials/NCT00003119">COG-P9641</a> and <a href="/clinicaltrials/NCT00003093">COG-A3961</a>): </p> <div class="pdq-content-list"><ol id="_182"><li>If the biology is completely favorable, metastasis is in a 4S pattern, and the re
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      9. context exact
        emotherapy.[<a href="#cit/section_10.19">19</a>]</p> <p id="_804" tabindex="-1">A COG study for intermediate-risk neuroblastoma (<a href="/clinicaltrials/NCT00003093">COG-A3961</a>) enrolled 479 patients, 42 of whom developed disease progression. The recurrence rate was 10% for those with favorable biology and 17% for those
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      source title
      Neuroblastoma Treatment (PDQ®)–Health Professional Version
      source update dates
      1. context
        Updated: April 28, 2025
        datetime
        2025-04-28T12:00:00Z
        display
        April 28, 2025

    Preserved source evidence · Not medical advice