Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Related Publications
Trial Contact Information
Registry Information

Alternate Title

Chemotherapy and Radiation Therapy With or Without Peripheral Stem Cell Transplantation in Treating Patients With Neuroblastoma

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Closed 20 and under Other GPOH-GERMANY-NB97 EU-20102, GER-GPOH-NB97, NCT00017225

Objectives

1. Determine the frequency of spontaneous remission in pediatric patients with localized neuroblastoma.
2. Determine the course of regression in patients with spontaneous remission.
3. Determine the event-free survival rate of patients with high-risk neuroblastoma treated with maintenance chemotherapy OR consolidation chemotherapy followed by autologous stem cell rescue.
4. Determine if a correlation exists between long-term overall survival and catecholamine response in these high-risk patients.
5. Determine if a correlation exists between cytotoxic and conditioning chemotherapies, in terms of bone marrow toxicity, in these high-risk patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed neuroblastoma



• Observation stratum:
  • MYCN gene not amplified
  • Infants with stage I-IVS disease

    OR

  • Over 1 year of age and stage I or II resectable disease



• Standard-risk stratum:
  • MYCN gene not amplified
  • Infants with serious symptoms and stage II-IVS disease

    OR

  • Over 1 year of age with stage II or III unresectable disease



• High-risk stratum:
  • Stage IV disease

    OR

  • Stage I-IVS MYCN gene-amplified disease

Prior/Concurrent Therapy:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy within 6 months after diagnosis

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified

Patient Characteristics:

Age:

• 20 and under

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• No kidney insufficiency

Cardiovascular:

• No cardiac insufficiency

Other:

• Not pregnant
• Fertile patients must use effective contraception
• No other serious illness

Expected Enrollment

Approximately 130 patients (50 in high-risk stratum, 15 in standard-risk stratum, and 65 in observation stratum) will be accrued for this study within 1 year.

Outline

This is a multicenter study. Patients are stratified according to risk (low vs standard vs high).

• Observation stratum (low risk): Patients undergo surgical biopsy followed by observation for 6-12 months. Patients may also undergo second-look surgery. Patients with tumor regression receive no further therapy. Patients with disease progression or no tumor regression receive standard-risk chemotherapy as in the standard-risk stratum.



• Standard-risk stratum: Patients undergo surgical biopsy.

  Patients at least 6 months of age receive 1 course of chemotherapy comprising cisplatin IV and etoposide IV continuously on days 1-4 and vindesine IV over 1 hour on day 1. Patients then receive 1 course of chemotherapy comprising vincristine IV over 1 hour on days 1 and 8, dacarbazine IV over 1 hour on days 1-5, ifosfamide IV continuously on days 1-5, and doxorubicin IV over 4 hours on days 6 and 7.

  Patients under 6 months of age receive doxorubicin IV over 30 minutes and vincristine IV on days 1, 3, and 5 and cyclophosphamide IV over 5 minutes on days 1-7. Treatment repeats every 3 weeks for 2 courses in the absence of unacceptable toxicity.

  After chemotherapy, patients may undergo second-look surgery followed by 2 additional courses of chemotherapy as above. Patients with complete response or very good partial response receive no further therapy. Patients with partial response, minimal response, no response, or progressive disease undergo local radiotherapy daily 5 days a week for approximately 6 weeks. Patients with no response after radiotherapy may then receive therapy as in the high-risk stratum.




• High-risk stratum: Patients undergo surgical biopsy.

  Patients at least 6 months of age receive induction chemotherapy comprising cisplatin, etoposide, and vindesine as in the standard-risk stratum combined with filgrastim (G-CSF) subcutaneously (SC) daily beginning on day 8 and continuing until blood counts recover. Patients also receive alternating courses of vincristine, dacarbazine, ifosfamide, and doxorubicin as in the standard-risk stratum combined with G-CSF SC daily beginning on day 9 and continuing until blood counts recover. Treatment repeats every 3 weeks for up to 6 courses in the absence of unacceptable toxicity.

  Patients under 6 months of age receive 2 courses of induction chemotherapy as in the standard-risk stratum followed by 4 courses of alternating chemotherapy as above.

  Patients may also undergo second-look surgery.

  Patients then receive consolidation chemotherapy comprising melphalan IV over 30 minutes on days -8 to -5, etoposide IV over 4 hours on day -4, and carboplatin IV over 1 hour on days -4 to -2. Patients undergo autologous stem cell transplantation (ASCT) on day 0. Patients also receive G-CSF SC or IV over 2 hours daily beginning on day 0. Patients may then undergo radiotherapy daily 5 days a week for 6 weeks.

  Patients who were diagnosed less than 1 year ago and who do not demonstrate MYCN amplication receive maintenance chemotherapy comprising oral cyclophosphamide on days 1-8 (instead of consolidation chemotherapy and ASCT as above). Treatment repeats every 3 weeks for 4 courses.

  Beginning 4-6 weeks after transplantation or 4 weeks after initiation of the last course of maintenance chemotherapy, all patients receive consolidation therapy with oral tretinoin 3 times daily on days 1-14. Treatment repeats every 28 days for 6 courses followed by a 3-month rest. Patients then receive 3 additional courses.

Patients are followed at 6 weeks, every 3 months for 5 years, and then every 6 months thereafter.

Simon T, Hero B, Bongartz R, et al.: Intensified external-beam radiation therapy improves the outcome of stage 4 neuroblastoma in children > 1 year with residual local disease. Strahlenther Onkol 182 (7): 389-94, 2006.[PUBMED Abstract]

Kremens B, Hero B, Esser J, et al.: Ocular symptoms in children treated with human-mouse chimeric anti-GD2 mAb ch14.18 for neuroblastoma. Cancer Immunol Immunother 51 (2): 107-10, 2002.[PUBMED Abstract]

Krams M, Hero B, Berthold F, et al.: Proliferation marker KI-S5 discriminates between favorable and adverse prognosis in advanced stages of neuroblastoma with and without MYCN amplification. Cancer 94 (3): 854-61, 2002.[PUBMED Abstract]

Simon T, Hero B, Dupuis W, et al.: The incidence of hearing impairment after successful treatment of neuroblastoma. Klin Padiatr 214 (4): 149-52, 2002 Jul-Aug.[PUBMED Abstract]

Spitz R, Hero B, Westermann F, et al.: Fluorescence in situ hybridization analyses of chromosome band 1p36 in neuroblastoma detect two classes of alterations. Genes Chromosomes Cancer 34 (3): 299-305, 2002.[PUBMED Abstract]

Hero B, Simon T, Spitz R, et al.: Localized infant neuroblastomas often show spontaneous regression: results of the prospective trials NB95-S and NB97. J Clin Oncol 26 (9): 1504-10, 2008.[PUBMED Abstract]

Simon T, Hero B, Benz-Bohm G, et al.: Review of image defined risk factors in localized neuroblastoma patients: Results of the GPOH NB97 trial. Pediatr Blood Cancer 50 (5): 965-9, 2008.[PUBMED Abstract]

Berthold F, Hero B, Kremens B, et al.: Long-term results and risk profiles of patients in five consecutive trials (1979-1997) with stage 4 neuroblastoma over 1 year of age. Cancer Lett 197 (1-2): 11-7, 2003.[PUBMED Abstract]

Spitz R, Hero B, Ernestus K, et al.: Deletions in chromosome arms 3p and 11q are new prognostic markers in localized and 4s neuroblastoma. Clin Cancer Res 9 (1): 52-8, 2003.[PUBMED Abstract]

Spitz R, Hero B, Ernestus K, et al.: FISH analyses for alterations in chromosomes 1, 2, 3, and 11 define high-risk groups in neuroblastoma. Med Pediatr Oncol 41 (1): 30-5, 2003.[PUBMED Abstract]

Spitz R, Hero B, Ernestus K, et al.: Gain of distal chromosome arm 17q is not associated with poor prognosis in neuroblastoma. Clin Cancer Res 9 (13): 4835-40, 2003.[PUBMED Abstract]

von Schweinitz D, Hero B, Berthold F: The impact of surgical radicality on outcome in childhood neuroblastoma. Eur J Pediatr Surg 12 (6): 402-9, 2002.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Gesellschaft fuer Paediatrische Onkologie und Haematologie - Germany

Frank Berthold, MD, Protocol chair		Ph: 49-221-478-4380 Email: frank.berthold@uk-koeln.de

Registry Information
Official Title		Neuroblastoma Study Phase II Study of Various Therapies in Patients with Neuroblastoma
Trial Start Date		1997-05-01
Registered in ClinicalTrials.gov		NCT00017225
Date Submitted to PDQ		2001-04-11
Information Last Verified		2002-08-30

Back to Top