Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Related Publications
Trial Contact Information
| Phase | Type | Status | Age | Sponsor | Protocol IDs |
|---|---|---|---|---|---|
| Phase III | Treatment | Completed | 30 and under | NCI | POG-8850 CCG-7881, INT-0091 |
Objectives
I. Compare event-free survival and survival among patients with newly diagnosed localized Ewing's sarcoma or primitive neuroectodermal tumors of the bone randomly assigned to standard therapy with VAC (vincristine/doxorubicin or dactinomycin/cyclophosphamide) vs. VAC combined with ifosfamide/etoposide, both groups also receiving local therapy with surgery and/or radiotherapy. II. Determine the toxicity of an intensified regimen of ifosfamide/vincristine/continuous-infusion doxorubicin/cyclophosphamide with granulocyte colony stimulating factor in children with metastatic disease. III. Compare the incidence of serious toxicities and adverse orthopedic outcomes in these treatment groups. IV. Evaluate the significance of tumor site, tumor size, histologic subtype, and electron microscopic pattern in determining response to therapy and ultimate outcome. V. Correlate imaging features observed at diagnosis and sequentially throughout therapy with response to therapy, prognosis, adequacy of radiotherapy volume, and survival (special emphasis will be placed on MRI studies, where available). VI. Determine the prognostic value of cellular DNA content and chromosomal changes, including the t(11;22)(q23;q11) translocation.
Entry Criteria
Disease Characteristics:
Newly diagnosed Ewing's sarcoma, primitive neuroectodermal tumor of a bone, or a diagnosis compatible with primitive sarcoma of bone (as of 12/8/92, only patients with metastatic disease are eligible) No extraosseous tumors Tumors must satisfy the following pathologic criteria: Light microscopic appearance of small round cell neoplasm with the primary in bone H and E staining under light microscopy consistent with Ewing's sarcoma, primitive neuroectodermal tumor of bone, or any other primitive sarcoma of bone No immunohistochemical or ultrastructural evidence to exclude the foregoing light microscopic diagnosis
Prior/Concurrent Therapy:
Biologic therapy: Not specified Chemotherapy: No prior chemotherapy Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy Surgery: Diagnostic biopsy within 1 month prior to registration Complete or partial resection discouraged but allowed
Patient Characteristics:
Age:
No more than 30
Performance status:
Not specified
Hematopoietic:
ANC more than 1,200 (unless marrow involved with tumor)
Platelets more than 150,000 (unless marrow involved with
tumor)
Hepatic:
Bilirubin less than 1.5 x ULN
Renal:
Creatinine normal for age
Cardiovascular:
Normal cardiac function
Expected Enrollment
About 400 patients will be entered over 4 years.
Outline
Randomized study. Patients with metastatic disease at diagnosis are treated on Regimen A. As of 12/8/92, the study is closed for randomized therapy and only Regimen A remains open. Arm I (arm closed as of 12/8/92). Induction: 3-Drug Combination Chemotherapy with Urothelial Protection. VAC: Vincristine, VCR, NSC-67574; Doxorubicin, DOX, NSC-123127; Cyclophosphamide, CTX, NSC-26271; with Mesna, NSC-113891. Local Therapy Phase: Surgery and/or Radiotherapy plus 3-Drug Combination Chemotherapy with Urothelial Protection. Appropriate surgical resection and/or involved-field irradiation using Co60 equipment or 4-25 MV accelerator beams (or electrons if indicated); plus VAC; with Mesna. Maintenance: 3-Drug Combination Chemotherapy with Urothelial Protection. VAC (with DOX or Dactinomycin, DACT, NSC-3053); with Mesna. Arm II (arm closed as of 12/8/92). Induction: 2-Drug Combination Chemotherapy with Urothelial Protection alternating with 3-Drug Combination Chemotherapy with Urothelial Protection. VP-16/IFF: Etoposide, VP-16, NSC-141540; Ifosfamide, IFF, NSC-109724; with Mesna; alternating with VAC; with Mesna. Local Therapy Phase: Surgery and/or Radiotherapy plus 3-Drug Combination Chemotherapy with Urothelial Protection followed by 2-Drug Combination Chemotherapy with Urothelial Protection. Surgical resection and/or involved-field irradiation as on Arm I; plus VAC; with Mesna; followed by VP-16/IFF; with Mesna. Maintenance: 3-Drug Combination Chemotherapy with Urothelial Protection alternating with 2-Drug Combination Chemotherapy with Urothelial Protection. VAC (with DOX or DACT); with Mesna; alternating with VP-16/IFF; with Mesna. Regimen A (dose-intense courses). Induction: 3-Drug Combination Chemotherapy with Urothelial Protection and Hematologic Toxicity Attenuation alternating with 2-Drug Combination Chemotherapy with Urothelial Protection and Hematologic Toxicity Attenuation. VAC; with Mesna; and Granulocyte Colony Stimulating Factor (Amgen), G-CSF, NSC-614629; alternating with VP-16/IFF; with Mesna; and G-CSF. Local Primary Control: Surgery and/or Radiotherapy plus 3-Drug Combination Chemotherapy with Urothelial Protection and Hematologic Toxicity Attenuation followed by 2-Drug Combination Chemotherapy with Urothelial Protection and Hematologic Toxicity Attenuation. Surgical resection and/or involved-field irradiation as on Arm I Local Therapy Phase; plus VAC; with Mesna; and G-CSF; followed by VP-16/IFF; with Mesna; and G-CSF. Interval Therapy: 3-Drug Combination Chemotherapy with Urothelial Protection and Hematologic Toxicity Attenuation alternating with 2-Drug Combination Chemotherapy with Urothelial Protection and Hematologic Toxicity Attenuation. VAC (with DOX or DACT, as indicated); with Mesna; and G-CSF; alternating with VP-16/IFF; with Mesna; and G-CSF. Local Metastasis Control: Surgery and/or Radiotherapy plus 3-Drug Combination Chemotherapy with Urothelial Protection and Hematologic Toxicity Attenuation followed by 2-Drug Combination Chemotherapy with Urothelial Protection and Hematologic Toxicity Attenuation. Surgical resection and/or involved-field irradiation as in Arm I Local Therapy Phase; plus VAC (with DACT); with Mesna; and G-CSF; followed by VP-16/IFF; with Mesna; G-CSF. Maintenance: 3-Drug Combination Chemotherapy with Urothelial Protection and Hematologic Toxicity Attenuation alternating with 2-Drug Combination Chemotherapy with Urothelial Protection and Hematologic Toxicity Attenuation. VAC (with DACT); with Mesna; and G-CSF; alternating with VP-16/IFF; with Mesna; G-CSF.Published Results
Granowetter L, Womer R, Devidas M, et al.: Dose-intensified compared with standard chemotherapy for nonmetastatic Ewing sarcoma family of tumors: a Children's Oncology Group Study. J Clin Oncol 27 (15): 2536-41, 2009.[PUBMED Abstract]
Leavey PJ, Mascarenhas L, Marina N, et al.: Prognostic factors for patients with Ewing sarcoma (EWS) at first recurrence following multi-modality therapy: A report from the Children's Oncology Group. Pediatr Blood Cancer 51 (3): 334-8, 2008.[PUBMED Abstract]
Bhatia S, Krailo MD, Chen Z, et al.: Therapy-related myelodysplasia and acute myeloid leukemia after Ewing sarcoma and primitive neuroectodermal tumor of bone: A report from the Children's Oncology Group. Blood 109 (1): 46-51, 2007.[PUBMED Abstract]
DuBois SG, Krailo MD, Cook EF, et al.: Evaluation of local control in patients with non-metastatic Ewing sarcoma of the bone: a report from the Children's Oncology Group. [Abstract] J Clin Oncol 25 (Suppl 18): A-10013, 548s, 2007.
Leavey P, Mascarenhas L, Marina N, et al.: Prognostic factors for patients with Ewing sarcoma (EWS) at first recurrence. [Abstract] J Clin Oncol 25 (Suppl 18): A-10011, 547s, 2007.
Miser JS, Goldsby RE, Chen Z, et al.: Treatment of metastatic Ewing sarcoma/primitive neuroectodermal tumor of bone: evaluation of increasing the dose intensity of chemotherapy--a report from the Children's Oncology Group. Pediatr Blood Cancer 49 (7): 894-900, 2007.[PUBMED Abstract]
Yock TI, Krailo M, Fryer CJ, et al.: Local control in pelvic Ewing sarcoma: analysis from INT-0091--a report from the Children's Oncology Group. J Clin Oncol 24 (24): 3838-43, 2006.[PUBMED Abstract]
Yock TI, Krailo MD, Grier HE, et al.: A comparison of local control achieved by surgery and radiotherapy in patients with non-metastatic pelvic Ewing sarcoma enrolled on INT-0091. [Abstract] Int J Radiat Oncol Biol Phys 60 (1 Suppl 1): A-192, S247, 2004.
Grier HE, Krailo MD, Tarbell NJ, et al.: Addition of ifosfamide and etoposide to standard chemotherapy for Ewing's sarcoma and primitive neuroectodermal tumor of bone. N Engl J Med 348 (8): 694-701, 2003.[PUBMED Abstract]
Grier H, Krailo M, Link MP, et al.: Improved outcome in nonmetastatic Ewing's sarcoma (EWS) and PNET of bone with addition of ifosfamide (I) and etoposide (E) to vincristine (V), Adriamycin (AD), cyclophosphamide (C), and actinomycin (A). [Abstract] Proceedings of the American Society of Clinical Oncology 13: A1443, 1994.
Related PublicationsAskin FB, Perlman EJ: Neuroblastoma and peripheral neuroectodermal tumors. Am J Clin Pathol 109 (4 Suppl 1): S23-30, 1998.[PUBMED Abstract]
de Alava E, Kawai A, Healey JH, et al.: EWS-FLI1 fusion transcript structure is an independent determinant of prognosis in Ewing's sarcoma. J Clin Oncol 16 (4): 1248-55, 1998.[PUBMED Abstract]
Maale GE, Katz JA, Timmons CC, et al.: Persistent tumor in resected specimens after pretreatment with chemotherapy and radiation for Ewing's sarcoma: an indication for surgical therapy. [Abstract] Proceedings of the American Society of Clinical Oncology 13: A-1423, 416, 1994.
Trial Lead Organizations
Pediatric Oncology Group
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| Holcombe Grier, MD, Protocol chair | |
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Children's Cancer Group
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| James Miser, MD, Protocol chair | |
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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.
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