|Phase III||Treatment||Closed||under 21||NCI||POG-7898|
I. Determine whether removal of cyclophosphamide from VAC (vincristine/actinomycin-D/cyclophosphamide) jeopardizes disease control and survival in patients with completely resected, localized disease. II. Compare pulse VAC vs. cyclic-sequential vincristine plus actinomycin-D in patients with microscopic residual or regional disease. III. Compare the effect of pulse VAC vs. pulse VADRC (vincristine/adriamycin/cyclophosphamide) on remission rate, remission duration, and survival in patients with gross residual or metastatic disease. IV. Determine whether pulse VAC improves remission and survival in patients subjected to primary major amputation. V. Determine the efficacy of prophylactic local meningeal radiation with or without intrathecal chemotherapy in the prevention of direct meningeal extension of disease. VI. Determine whether primary chemotherapy and radiotherapy can replace radical surgery in rhabdomyosarcoma localized to the pelvis. VII. Study the frequency and significance of lymph node involvement in relation to primary tumor site.
See General Eligibility Criteria
See General Eligibility Criteria
General Eligibility Criteria:
Patients under 21 years of age with one of 4 cell types of rhabdomyosarcoma or with small cell mesenchymal or undifferentiated sarcoma. Patients must not have had prior chemotherapy or radiotherapy.
Estimated entry of patients per year in Clinical Groups 1 to 4 is 23, 31, 57, and 28, respectively. Protocol closed November 1984.
Randomized study. Separately randomize patients receiving primary chemotherapy and those receiving primary surgery. Patients with completely resected, localized disease (Group 1) are randomized to Arms I and II; those with microscopic residual or regional disease (Group 2) are randomized to Arms III and IV. Group 1 and 2 patients who require amputation enter Arm V. Patients with gross residual or metastatic disease (Groups 3 and 4) are randomized to Arms V and VI. Enter patients with primary pelvic disease to Arm VII when institution has elected primary chemotherapy. Enter patients with primary disease of the nasopharynx, nasal cavity, paranasal sinuses or middle ear with evidence of meningeal disease to Arm VIII. Enter those patients with skull erosion but negative CSF cytology to Arm IX. Addendum 1, March 1979. For all patients in Groups 1 and 2 with alveolar extremity primary tumors: pulse VAC therapy alone, as in Arm V, for Group 1; VAC therapy plus Radiotherapy beginning at 6 weeks for Group 2. Arm I: 3-Drug Combination Chemotherapy. VAC: Vincristine, VCR, NSC-67574; Actinomycin-D, ACT-D, NSC-3053; Cyclophosphamide, CTX, NSC-26271. Arm II: 2-Drug Combination Chemotherapy. VCR, ACT-D. Arm III: 2-Drug Combination Chemotherapy plus Radiotherapy. VCR, ACT-D; plus supervoltage irradiation. Arm IV: 3-Drug Combination Chemotherapy plus Radiotherapy. VAC; plus supervoltage irradiation. Arm V: 3-Drug Combination Chemotherapy plus Radiotherapy. VAC; plus supervoltage irradiation. Arm VI: Alternating 3-Drug Combination Chemotherapies plus Radiotherapy. VADRC: VCR; CTX; Adriamycin, ADR, NSC-123127; alternating with VAC. Arm VII: 3-Drug Combination Chemotherapy plus Surgery or Radiotherapy. VAC; plus tumor resection or supervoltage irradiation. Arm VIII: 4-Drug Combination Chemotherapy plus Radiotherapy. Cytosine arabinoside, ARA-C, NSC-63878; Hydrocortisone, HC, NSC-10483; Methotrexate, MTX, NSC-740; Citrovorum factor, CF, NSC-3590; plus supervoltage irradiation. Arm IX: 4-Drug Combination Chemotherapy plus Radiotherapy. ARA-C; HC; MTX; CF; plus supervoltage irradiation.Published Results
Wharam MD, Hanfelt JJ, Tefft MC, et al.: Radiation therapy for rhabdomyosarcoma: local failure risk for Clinical Group III patients on Intergroup Rhabdomyosarcoma Study II. Int J Radiat Oncol Biol Phys 38 (4): 797-804, 1997.[PUBMED Abstract]
Maurer HM, Gehan EA, Beltangady M, et al.: The Intergroup Rhabdomyosarcoma Study-II. Cancer 71 (5): 1904-22, 1993.[PUBMED Abstract]
Hays DM, Lawrence W Jr, Wharam M, et al.: Primary reexcision for patients with 'microscopic residual' tumor following initial excision of sarcomas of trunk and extremity sites. J Pediatr Surg 24 (1): 5-10, 1989.[PUBMED Abstract]Related Publications
Million L, Anderson J, Breneman J, et al.: Influence of noncompliance with radiation therapy protocol guidelines and operative bed recurrences for children with rhabdomyosarcoma and microscopic residual disease: a report from the Children's Oncology Group. Int J Radiat Oncol Biol Phys 80 (2): 333-8, 2011.[PUBMED Abstract]
Huh WW, Anderson JR, Rodeberg D, et al.: Orbital sarcoma with metastases at diagnosis: a report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group. Pediatr Blood Cancer 54 (7): 1045-7, 2010.[PUBMED Abstract]
Hayes-Jordan A, Stoner JA, Anderson JR, et al.: The impact of surgical excision in chest wall rhabdomyosarcoma: a report from the Children's Oncology Group. J Pediatr Surg 43 (5): 831-6, 2008.[PUBMED Abstract]
Qualman S, Lynch J, Bridge J, et al.: Prevalence and clinical impact of anaplasia in childhood rhabdomyosarcoma : a report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group. Cancer 113 (11): 3242-7, 2008.[PUBMED Abstract]
Raney RB, Meza J, Anderson JR, et al.: Treatment of children and adolescents with localized parameningeal sarcoma: experience of the Intergroup Rhabdomyosarcoma Study Group protocols IRS-II through -IV, 1978-1997. Med Pediatr Oncol 38 (1): 22-32, 2002.[PUBMED Abstract]
Walterhouse D, Pappo A, Baker S, et al.: Rhabdomyosarcoma of the parotid region: a report of the Intergroup Rhabdomyosarcoma Study (IRS) Group, studies I to IV. [Abstract] Proceedings of the American Society of Clinical Oncology 19: A2340, 2000.
Raney RB, Asmar L, Vassilopoulou-Sellin R, et al.: Late complications of therapy in 213 children with localized, nonorbital soft-tissue sarcoma of the head and neck: A descriptive report from the Intergroup Rhabdomyosarcoma Studies (IRS)-II and - III. IRS Group of the Children's Cancer Group and the Pediatric Oncology Group. Med Pediatr Oncol 33 (4): 362-71, 1999.[PUBMED Abstract]
Wolden SL, Anderson JR, Crist WM, et al.: Indications for radiotherapy and chemotherapy after complete resection in rhabdomyosarcoma: A report from the Intergroup Rhabdomyosarcoma Studies I to III. J Clin Oncol 17 (11): 3468-75, 1999.[PUBMED Abstract]
Kodet R, Newton WA Jr, Hamoudi AB, et al.: Orbital rhabdomyosarcomas and related tumors in childhood: relationship of morphology to prognosis--an Intergroup Rhabdomyosarcoma study. Med Pediatr Oncol 29 (1): 51-60, 1997.[PUBMED Abstract]
Lawrence W Jr, Anderson JR, Gehan EA, et al.: Pretreatment TNM staging of childhood rhabdomyosarcoma: a report of the Intergroup Rhabdomyosarcoma Study Group. Children's Cancer Study Group. Pediatric Oncology Group. Cancer 80 (6): 1165-70, 1997.[PUBMED Abstract]
Hays DM, Raney RB, Wharam MD, et al.: Children with vesical rhabdomyosarcoma (RMS) treated by partial cystectomy with neoadjuvant or adjuvant chemotherapy, with or without radiotherapy. A report from the Intergroup Rhabdomyosarcoma Study (IRS) Committee. J Pediatr Hematol Oncol 17 (1): 46-52, 1995.[PUBMED Abstract]
Raney RB, Asmar L, Vassilopoulou-Sellin R, et al.: Late sequelae in 162 patients with non-orbital soft-tissue sarcoma of the head and neck: report from Intergroup Rhabdomyosarcoma Studies (IRS) -II and -III. [Abstract] Proceedings of the American Society of Clinical Oncology 14: A-1459, 454, 1995.
Douglass EC, Shapiro DN, Valentine M, et al.: Alveolar rhabdomyosarcoma with the t(2;13): cytogenetic findings and clinicopathologic correlations. Med Pediatr Oncol 21 (2): 83-7, 1993.[PUBMED Abstract]
Shapiro DN, Parham DM, Douglass EC, et al.: Relationship of tumor-cell ploidy to histologic subtype and treatment outcome in children and adolescents with unresectable rhabdomyosarcoma. J Clin Oncol 9 (1): 159-66, 1991.[PUBMED Abstract]
Crist WM, Garnsey L, Beltangady MS, et al.: Prognosis in children with rhabdomyosarcoma: a report of the intergroup rhabdomyosarcoma studies I and II. Intergroup Rhabdomyosarcoma Committee. J Clin Oncol 8 (3): 443-52, 1990.[PUBMED Abstract]
Newton WA Jr, Soule EH, Hamoudi AB, et al.: Histopathology of childhood sarcomas, Intergroup Rhabdomyosarcoma Studies I and II: clinicopathologic correlation. J Clin Oncol 6 (1): 67-75, 1988.[PUBMED Abstract]
Trial Lead Organizations
Pediatric Oncology Group
|Harold Maurer, MD, Protocol chair|
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.