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Combination Chemotherapy in Treating Children With Neuroblastoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00003093
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : August 1, 2014
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Study Description
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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.


Condition or disease Intervention/treatment Phase
Neuroblastoma Biological: filgrastim Biological: sargramostim Drug: carboplatin Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: etoposide Procedure: conventional surgery Procedure: neoadjuvant therapy Phase 3

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 573 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Treatment for Infants and Children With Intermediate Risk Neuroblastoma: A Phase III Intergroup CCG/POG Study
Study Start Date : March 1988
Actual Primary Completion Date : September 2006
Actual Study Completion Date : January 2011

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Neuroblastoma

Arms and Interventions
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Arm Intervention/treatment
Experimental: Treatment
See detailed description.
 Biological: filgrastim
Other Names:
  • Granulocyte Colony-Stimulating Factor
  • r-metHuG-CSF
  • G-CSF
  • Neupogen®
  • NSC #614629

Biological: sargramostim
Other Names:
  • Granulocyte Macrophage-Colony Stimulating Factor
  • rhu GM-CSF
  • GM-CSF
  • Prokine
  • Leukine
  • NSC #613795

Drug: carboplatin
Other Names:
  • Paraplatin
  • NSC-241240

Drug: cyclophosphamide
Other Names:
  • Cytoxan
  • NSC-26271

Drug: doxorubicin hydrochloride
Other Names:
  • Adriamycin
  • NSC-123127

Drug: etoposide
Other Names:
  • VP-16
  • VePesid
  • NSC-141540

Procedure: conventional surgery
Procedure: neoadjuvant therapy


Outcome Measures
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Primary Outcome Measures :
  1. Event Free Survival

Eligibility Criteria
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Ages Eligible for Study:   up to 20 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00003093


Locations
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Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
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Study Chair: David L. Baker, MD, MBBS, FRACP, FRCPA Princess Margaret Hospital for Children
More Information
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Publications of Results:
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.

Other Publications:
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.
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.

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Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00003093    
Other Study ID Numbers: A3961
COG-A3961 ( Other Identifier: Children's Oncology Group )
CCG-A3961 ( Other Identifier: Children's Cancer Group )
POG-A3961 ( Other Identifier: Pediatric Oncology Group )
CDR0000065804 ( Other Identifier: Clinical Trials.gov )
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: August 1, 2014
Last Verified: July 2014
Keywords provided by Children's Oncology Group:
regional neuroblastoma
disseminated neuroblastoma
stage 4S neuroblastoma
localized unresectable neuroblastoma
Additional relevant MeSH terms:
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Neuroblastoma
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Cyclophosphamide
Carboplatin
Doxorubicin
Liposomal doxorubicin
Etoposide
 Molgramostim
Lenograstim
Sargramostim
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors