Observation, Combination Chemotherapy, Radiation Therapy, and/or Autologous Stem Cell Transplant in Treating Young Patients With Neuroblastoma - Full Text View

Purpose

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving combination chemotherapy may kill more tumor cells. Radiation therapy uses high-energy x-rays to kill tumor cells. An autologous stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy and radiation therapy. This may allow more chemotherapy to be given so that more tumor cells are killed. Sometimes, after surgery, the tumor may not need more treatment until it progresses. In this case, observation may be sufficient. It is not yet known whether observation is more effective than combination chemotherapy, radiation therapy, and/or autologous stem cell transplant in treating neuroblastoma.

PURPOSE: This randomized phase III and phase IV trial is studying observation, combination chemotherapy, radiation therapy, and/or autologous stem cell transplant to compare how well they work in treating young patients with neuroblastoma.

Condition	Intervention	Phase
Neuroblastoma	Biological: filgrastim Drug: carboplatin Drug: cisplatin Drug: cyclophosphamide Drug: dacarbazine Drug: doxorubicin hydrochloride Drug: etoposide phosphate Drug: ifosfamide Drug: isotretinoin Drug: melphalan Drug: topotecan hydrochloride Drug: vincristine sulfate Drug: vindesine Procedure: autologous hematopoietic stem cell transplantation Procedure: conventional surgery Procedure: peripheral blood stem cell transplantation Radiation: iobenguane I 131 Radiation: radiation therapy	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Masking: Open Label Primary Purpose: Treatment
Official Title:	NB2004 Trial Protocol for Risk Adapted Treatment of Children With Neuroblastoma

Resource links provided by NLM:

Genetics Home Reference related topics: neuroblastoma

MedlinePlus related topics: Cancer Neuroblastoma

Drug Information available for: Cyclophosphamide Melphalan Vincristine sulfate Melphalan hydrochloride Ifosfamide Dacarbazine Isotretinoin Cisplatin Doxorubicin Doxorubicin hydrochloride Etoposide Carboplatin Etoposide phosphate Topotecan hydrochloride Filgrastim Topotecan Lenograstim Granulocyte colony-stimulating factor

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Event-free survival (EFS) [ Designated as safety issue: No ]
Locoregional EFS [ Designated as safety issue: No ]

Secondary Outcome Measures:

Time from diagnosis to transition to stage 4 disease, to death from disease, or to the last follow-up (if no transition to stage 4 disease is observed) [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]
Time to the beginning of primary tumor regression (in patients in the low-risk group [LRG]) [ Designated as safety issue: No ]
Time to the normalization of tumor markers HVA and VMA in urine [ Designated as safety issue: No ]
Time to no evidence of disease (in patients in the LRG with stage 4S disease) [ Designated as safety issue: No ]
Status of the primary tumor 12 months after diagnosis (LRG) [ Designated as safety issue: No ]
Best status of the primary tumor within the first 12 months (LRG) [ Designated as safety issue: No ]
Status of chromosome 1p (unblinded) and status of chromosome 11q (blinded) [ Designated as safety issue: No ]
Comparison of the extent of initial surgery (incomplete resection vs macroscopic complete resection) (LRG) [ Designated as safety issue: No ]
Comparison of the extent of best surgery during protocol treatment (incomplete resection vs macroscopic complete resection) [ Designated as safety issue: No ]
Surgery-related complications (i.e., bleeding, infection, intestinal obstruction, or other) [ Designated as safety issue: No ]
Disease progression and symptoms controlled after the first, second, third, and fourth N4 course (LRG) [ Designated as safety issue: No ]
Disease progression and symptoms not controlled after four N4 courses (LRG) [ Designated as safety issue: No ]
Transition to stage 4 disease at any time (LRG) [ Designated as safety issue: No ]
Acute and late side effects of external-beam radiotherapy (medium-risk group [MRG] and high-risk group [HRG]) [ Designated as safety issue: Yes ]
Early response after 2 courses of induction therapy (N5 and N6 or two courses of N8) (HRG) [ Designated as safety issue: No ]
Response to induction therapy prior to conditioning therapy or after 280 days (HRG) [ Designated as safety issue: No ]
Grade of toxicity observed during induction therapy course 1 (N5 or N8) (HRG) [ Designated as safety issue: Yes ]
Grade of toxicity observed during induction therapy course 2 (N6 or N8) (HRG) [ Designated as safety issue: Yes ]
Frequency of grade 3 or 4 toxicity observed during the last 6 courses of induction therapy (3 courses of N5 and N6) (HRG) [ Designated as safety issue: Yes ]
Activity and whole body dose of radiotherapy [ Designated as safety issue: No ]

Estimated Enrollment:	642
Study Start Date:	October 2004
Estimated Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Show Detailed Description

Eligibility

Ages Eligible for Study:	up to 21 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of neuroblastoma by histology using tumor tissue or as evidenced by the presence of distinct neuroblastoma cells in the bone marrow AND elevated catecholamine metabolites (i.e., homovanillic acid [HVA] and vanillylmandelic acid [VMA]) in blood or urine
- Newly diagnosed disease (for patients in the low-risk group)
- Diagnosis from tumor tissue (for patients in the medium-risk group)
Meets criteria for 1 of the following risk groups:
- Low-risk group
  - No MYCN amplification AND meets 1 of the following criteria:
    - Stage 1 disease
    - Stage 2 disease with no chromosome 1p deletion or imbalance
    - Stage 3 disease with no chromosome 1p deletion or imbalance (for patients < 2 years of age)
    - Stage 4S disease (for patients < 1 year of age)
- Medium-risk group
  - No MYCN amplification AND meets 1 of the following criteria:
    - Stage 2 disease with chromosome 1p deletion or imbalance
    - Stage 3 disease with chromosome 1p deletion or imbalance
      - Any chromosome 1p status (for patients ≥ 2 years of age)
    - Stage 4 disease (for patients < 1 year of age)
- High-risk group, meeting 1 of the following criteria:
  - Any stage disease with MYCN amplification
    - Any MYCN status (for patients ≥ 1 year of age)

PATIENT CHARACTERISTICS:

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

No prior nephrectomy or other mutilating surgery as initial surgery (for patients in the low-risk group)
No other concurrent anticancer therapy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00410631

Show 80 Study Locations

Sponsors and Collaborators

Gesellschaft fur Padiatrische Onkologie und Hamatologie - Germany

Investigators

Study Chair:

Frank Berthold, MD

Children's Hospital Medical Center, Cincinnati

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

ClinicalTrials.gov Identifier:	NCT00410631 History of Changes
Other Study ID Numbers:	CDR0000517312, GPOH-NB2004, EU-20661
Study First Received:	December 11, 2006
Last Updated:	May 7, 2009
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

localized resectable neuroblastoma
localized unresectable neuroblastoma
regional neuroblastoma

stage 4S neuroblastoma
disseminated neuroblastoma
recurrent neuroblastoma

Additional relevant MeSH terms:

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
Etoposide phosphate
Isophosphamide mustard
Cisplatin
Cyclophosphamide
Dacarbazine

Doxorubicin
Etoposide
Ifosfamide
Melphalan
Vincristine
Vindesine
3-Iodobenzylguanidine
Carboplatin
Topotecan
Lenograstim
Isotretinoin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on June 17, 2013