Phase III Management of Good-, Intermediate-, and Selected Poor-Prognosis Neuroblastomas on the Basis of Age, Stage, and Risk Factors
Last Modified: 11/26/2007
Basic Trial Information Objectives Entry Criteria Expected Enrollment Outline Published Results Related Publications Trial Contact Information
Basic Trial Information
Phase | Type | Status | Age | Protocol IDs |
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Phase III | Treatment | Completed | under 18 | CCG-3881
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Objectives
I. Evaluate in patients with favorable stages (Stages I, II, and IV-S) of
neuroblastoma the prognostic significance of a number of biological and
clinical factors, including serum ferritin, serum neuron-specific enolase, the
number of copies of the N-myc oncogene and N-myc protein expression in the
primary tumor and in bone marrow metastases, tumor histopathology, the
presence of subclinical involvement of the bone marrow as detected with
immunohistologic techniques, and regional lymph node involvement.
II. Determine whether "good-prognosis" neuroblastoma patients (i.e., patients
with Stage I disease and those with Stage II disease with fewer than 3 copies
of N-myc) have a 3-year progression-free survival (PFS) in excess of 90%
following surgery alone.
III. Determine whether "intermediate-prognosis" neuroblastoma patients (i.e.,
patients of any age with Stage III disease, favorable histopathology, fewer
than 3 copies of N-myc, and normal serum ferritin and patients under the age
of 1 year with Stage IV disease and neuron-specific enolase less than 100
ng/ml) have a 3-year PFS in excess of 70% with combination chemotherapy
together with surgery and radiotherapy for residual disease.
IV. Determine the PFS of selected "poor-prognosis" neuroblastoma patients
(i.e., Stage II patients under the age of 1 year with at least 3 copies of
N-myc, Stage III patients under the age of 1 year with unfavorable
histopathology, at least 3 copies of N-myc, or elevated serum ferritin, and
Stage IV patients under the age of 1 year with neuron-specific enolase of at
least 100 ng/ml) following treatment with combination chemotherapy together
with surgery and radiotherapy for residual disease.
V. Determine whether patients with Stage IV-S neuroblastoma have a 3-year PFS
in excess of 90% with standardized supportive care alone and whether those
requiring additional therapy can be identified at diagnosis.
Entry Criteria Disease Characteristics:
Newly diagnosed neuroblastoma in one of the following groups:
Stage I and less than 18 years of age
Stage II and less than 18 years of age
Children age 1 to 18 years found to have 10 or more copies of N-myc are
transferred to CCG-3891; transfer must occur within 6 weeks of diagnosis
Stage III and less than 18 years of age
Children age 1 to 18 years found to have unfavorable histology, 10 or
more copies of N-myc, or elevated ferritin are transferred to CCG-3891
Children under age 1 with unfavorable characteristics remain on this
study
Stage IV/IV-S and under 1 year
Infants subsequently found to have 10 or more copies of N-myc are
transferred to CCG-3891
Entry within 4 weeks of diagnosis or, as applicable, 96 hours of starting
induction chemotherapy required
Final determination of N-myc must be obtained from the Neuroblastoma Reference
Laboratory
Prior/Concurrent Therapy:
Biologic therapy:
No prior therapy
Chemotherapy:
No prior therapy (except as noted above for patients transferring from
CCG-3891)
Endocrine therapy:
No prior therapy
Radiotherapy:
No prior therapy
Surgery:
No prior therapy
Patient Characteristics:
Age:
Under 18 (see Disease Characteristics)
Performance status:
Not specified
Hematopoietic:
Not specified
Hepatic:
Not specified
Renal:
Not specified
Expected Enrollment
171 patients will be entered over approximately 3 years. Outline
All Stage I patients and Stage II patients with fewer than 10 copies of N-myc
are treated on Regimen A. Stage II patients under the age of 1 year with 10
or more copies of N-myc and all Stage III and Stage IV patients are treated on
Regimen B, and patients with Stage IV-S disease are managed on Regimen C.
Regimen A: Surgery plus (if indicated) Radiotherapy. Primary tumor
resection; plus (in selected cases of cord compression) irradiation of the
site of cord compression using megavoltage equipment.
Regimen B:
Dose-Intense Induction followed by Standard Induction. 4-Drug Combination
Chemotherapy. Cyclophosphamide, CTX, NSC-26271; Cisplatin, CDDP, NSC-119875;
Doxorubicin, DOX, NSC-123127; Etoposide, VP-16, NSC-141540; followed by the
same drugs at standard doses.
Consolidation: Surgery followed by 2-Drug Combination Chemotherapy plus
Radiotherapy. Total resection of residual disease or debulking as
appropriate; followed by a single course of CTX/VP-16; plus irradiation of
residual disease using Co60 or 4-10 MV photons (electron beams may be used for
appropriately superficial lesions).
Maintenance: 4-Drug Combination Chemotherapy followed by Surgery. CTX; DOX;
CDDP; VP-16; followed by resection of residual disease if appropriate.
Regimen C: Standardized supportive care with surgical intervention,
radiotherapy, and/or treatment with CTX as dictated by individual clinical
circumstances.
Published ResultsMatthay K, Lukens J, Stram D, et al.: Prognosis for stage IV neuroblastoma less than one year at diagnosis: a prospective Childrens Cancer Group study. [Abstract] Proceedings of the American Society of Clinical Oncology 14: A-1425, 446, 1995. Matthay KK, Stram D, Seeger RC, et al.: A prospective Childrens Cancer Group study of stage II neuroblastoma treated with surgery alone. [Abstract] Proceedings of the American Society of Clinical Oncology 12: A-1420, 414, 1993. Related PublicationsGurney JG, Tersak JM, Ness KK, et al.: Hearing loss, quality of life, and academic problems in long-term neuroblastoma survivors: a report from the Children's Oncology Group. Pediatrics 120 (5): e1229-36, 2007.[PUBMED Abstract] Kobayashi C, Monforte-Munoz HL, Gerbing RB, et al.: Enlarged and prominent nucleoli may be indicative of MYCN amplification: a study of neuroblastoma (Schwannian stroma-poor), undifferentiated/poorly differentiated subtype with high mitosis-karyorrhexis index. Cancer 103 (1): 174-80, 2005.[PUBMED Abstract] London WB, Castleberry RP, Matthay KK, et al.: Evidence for an age cut-off greater than 365 days for neuroblastoma risk group stratification in the Children's Oncology Group (COG). [Abstract] J Clin Oncol 23 (Suppl 16): A-8500, 800s, 2005. London WB, Castleberry RP, Matthay KK, et al.: Evidence for an age cutoff greater than 365 days for neuroblastoma risk group stratification in the Children's Oncology Group. J Clin Oncol 23 (27): 6459-65, 2005.[PUBMED Abstract] Shimada H, Umehara S, Monobe Y, et al.: International neuroblastoma pathology classification for prognostic evaluation of patients with peripheral neuroblastic tumors: a report from the Children's Cancer Group. Cancer 92 (9): 2451-61, 2001.[PUBMED Abstract] Umehara S, Nakagawa A, Matthay K, et al.: Ganglioneuroblastoma, nodular - prognostic subsets determined by histopathologic evaluation: a report from the Children's Cancer Group. [Abstract] Proceedings of the American Society of Clinical Oncology 19: A-2307, 2000. Matthay KK, Perez C, Seeger RC, et al.: Successful treatment of stage III neuroblastoma based on prospective biologic staging: a Children's Cancer Group study. J Clin Oncol 16 (4): 1256-64, 1998.[PUBMED Abstract] Haase GM, Atkinson JB, Stram DO, et al.: Surgical management and outcome of locoregional neuroblastoma: comparison of the Childrens Cancer Group and the international staging systems. J Pediatr Surg 30 (2): 289-94; discussion 295, 1995.[PUBMED Abstract] Matthay KK, Sather HN, Seeger RC, et al.: Excellent outcome of stage II neuroblastoma is independent of residual disease and radiation therapy. J Clin Oncol 7 (2): 236-44, 1989.[PUBMED Abstract]
Trial Contact Information
Trial Lead Organizations Children's Cancer Group | | | John Lukens, MD, Protocol chair(Contact information may not be current) | | Ph: 615-936-1782; 800-811-8480 |
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Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol. |