Phase III Management of Good-, Intermediate-, and Selected Poor-Prognosis Neuroblastomas on the Basis of Age, Stage, and Risk Factors
Basic Trial Information
|Phase III||Treatment||Completed||under 18||NCI||CCG-3881|
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.
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
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
Age: Under 18 (see Disease Characteristics) Performance status: Not specified Hematopoietic: Not specified Hepatic: Not specified Renal: Not specified
171 patients will be entered over approximately 3 years.
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.
Matthay 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.
Marachelian A, Shimada H, Sano H, et al.: The significance of serial histopathology in a residual mass for outcome of intermediate risk stage 3 neuroblastoma. Pediatr Blood Cancer 58 (5): 675-81, 2012.[PUBMED Abstract]
Gurney 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
Ph: 615-936-1782; 800-811-8480
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.