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Clinical Trials (PDQ®)

Phase III Combined Modality Therapy for Group I, II, and III Rhabdomyosarcoma

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

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IIITreatmentCompletedunder 21NCIIRS-III
CCG-631, POG-8451, INT-0032

Objectives

I.  Determine whether the 2-year relapse-free survival rate can be increased 
in patients with rhabdomyosarcoma with clinical Group I disease and favorable 
histology using cyclic-sequential courses of vincristine/actinomycin-D and 
whether one year of chemotherapy with 
vincristine/adriamycin/cyclophosphamide/actinomycin-D/cis-platinum plus 
postoperative radiation to the tumor bed will improve the 2-year relapse-free 
survival rate of Group I patients with unfavorable histology.
II.  Determine whether the addition of adriamycin pulses to cyclic-sequential 
vincristine/actinomycin-D increases the 2-year relapse-free survival rate in 
patients with Group II disease with favorable histology who also receive 
postoperative radiation to the tumor bed, and determine whether chemotherapy 
with VadrC (vincristine/adriamycin/cyclophosphamide) and VAC 
(vincristine/actinomycin-D/cyclophosphamide) plus cis-platinum increases the 
2-year relapse-free survival rate in Group II patients with unfavorable 
histology.
III.  Determine whether the addition of cis-platinum or cis-platinum/VP-16213 
to VadrC and VAC increases the complete response and relapse-free survival 
rates of patients with Group III disease who also receive irradiation to the 
tumor bed and sites of metastases.
IV.  Determine whether the use of second- and third-look surgery, performed to 
provide pathologic confirmation of the completeness of response and to resect 
residual tumor, improves local disease control in Group III patients.
V.  Determine whether chemotherapy with adriamycin/DTIC or 
actinomycin-D/VP-16213 or actinomycin-D/DTIC produces a complete response in 
patients with Group III disease who have achieved only a partial response with 
induction chemotherapy, radiation, and second surgery with incomplete tumor 
resection.
VI.  Attempt to improve the complete response rate, remission duration, and 
survival in patients with localized disease in the orbit or head (Groups II 
and III), selected head and neck sites, or selected pelvic sites.

Entry Criteria

Disease Characteristics:

See General Eligibility Criteria

Patient Characteristics:

See General Eligibility Criteria

General Eligibility Criteria:

Patients under 21 years of age with 
rhabdomyosarcoma or undifferentiated sarcoma, type indeterminate, or 
extraosseous Ewing's sarcoma.  Prior chemotherapy or radiotherapy is not 
allowed.  As of October 1988, study is closed to patients with Clinical Group 
IV disease and to Clinical Group III patients with tumors in the bladder, 
prostate, vagina, and uterus; such patients are now registered on POG-8788 and 
POG-8889.  The study remains open to patients with Clincal Groups I and II 
disease and to Clinical Group III patients with favorable histology 
(nonalveolar) head or paratestes primaries.

Expected Enrollment

The estimated entry per year in clinical Groups I, II, III, and IV is 14, 15, 
53, and 29 patients, respectively.  Patient entry per year for pelvic sites, 
unfavorable histologies, and orbit or head sites is expected to be 18, 25, and 
10 patients, respectively.  Study duration is estimated to be 4 years.  As of 
October, 1988, study is closed to Clincal Group IV patients and Clinical group 
III patients with special pelvic tumors (bladder, prostate, vagina, and 
uterus) and all other Group III patients except those with tumors of the 
orbit, scalp, parotid gland, oral cavity, larynx, oropharynx, and cheek.

Outline

Group I patients with favorable histology enter Regimen 31; Group I and II 
patients with unfavorable histology enter Regimen 38.  Group II patients with 
favorable histology are randomized to Regimens 32 and 33; Group III patients 
are randomized to Regimens 34, 35, and 36.  Special Group II and III patients 
(primaries in the orbit, scalp, parotid, oral cavity, larynx, oropharynx, and 
cheek) are assigned to Regimen 32.  Group III patients with primary disease in 
the dome of the bladder, the vagina, or uterus are assigned to Regimen 37A, 
and those with a primary in the bladder neck, bladder trigone region, or the 
prostate are assigned to Regimen 37B (Group III patients with pelvic primaries 
no longer eligible as of october, 1988).  Patients with cranial parameningeal 
sarcoma are concurrently treated with Cranial Therapy (as well as the regimen 
appropriate for their disease).  Therapy on all regimens must begin within 21 
days following the final surgical procedure or within 42 days of the initial 
surgical procedure (e.g., biopsy).
Regimen 31:  2-Drug Combination Chemotherapy.  Actinomycin-D, ACT-D, NSC-3053; 
Vincristine, VCR, NSC-67574.
Regimen 32:  Radiotherapy plus 2-Drug Combination Chemotherapy.  Postoperative 
tumor bed irradiation using megavoltage photons (Co60 or accelerator with beam 
energy of 4 MeV or greater); plus ACT-D; VCR.
Regimen 33:  Radiotherapy plus 3-Drug Combination Chemotherapy.  Postoperative 
tumor bed irradiation; plus ACT-D; VCR; Adriamycin, ADR, NSC-123127.
Regimen 34 (regimen closed as of October, 1988):  3-Drug Combination 
Chemotherapy plus Radiotherapy plus Surgery plus 2-Drug Combination 
Chemotherapy.  VAC:  VCR; ACT-D; Cyclophosphamide, CTX, NSC-26271; plus 
irradiation of the tumor bed and metastases; plus resection of local residual 
disease or pulmonary metastasis or surgical evaluation of disease response; 
plus ADR; DTIC, NSC-45388.
Regimen 35 (regimen closed as of October, 1988):  5-Drug Combination 
Chemotherapy plus Radiotherapy plus Surgery plus Two Alternating 3-Drug 
Chemotherapy Combinations plus 2-Drug Combination Chemotherapy.  VCR; ADR; 
CTX; cis-Platinum, CACP, NSC-119875; ACT-D; plus irradiation of tumor bed and 
metastases; plus resection or surgical evaluation as appropriate; plus VadrC:  
VCR; ADR; CTX; alternating with VAC; plus ACT-D; VP-16213, VP-16, NSC-141540.
Regimen 36 (regimen closed as of October, 1988):  6-Drug Combination 
Chemotherapy plus Radiotherapy plus Surgery plus Two Alternating 3-Drug 
Chemotherapy Combinations plus 2-Drug Combination Chemotherapy.  VCR; ADR; 
CTX; CACP; VP-16; ACT-D; plus irradiation of tumor bed and metastases; plus 
resection or surgical evaluation as appropriate; plus VadrC alternating with 
VAC; plus ACT-D; DTIC.
Regimen 37A (regimen closed as of October, 1988):  Therapy as on Regimen 35 on 
an altered schedule.
Regimen 37B (regimen closed as of October, 1988):  Therapy as on Regimen 35 on 
an altered schedule.
Regimen 38:  4-Drug Combination Chemotherapy plus Radiotherapy plus Two 
Alternating 3-Drug Chemotherapy Combinations.  VCR; CACP; ADR; CTX; plus 
irradiation of the tumor bed; plus VadrC alternating with VAC.
Cranial Therapy:  Radiotherapy plus Triple Intrathecal Therapy (TIT) with 
Leucovorin Rescue.  Cranial and primary tumor irradiation; plus it 
Methotrexate, MTX, NSC-740; Hydrocortisone, HC, NSC-10483; Cytosine 
arabinoside, ARA-C, NSC-63878; with Citrovorum Factor, CF, NSC-3590.

Published Results

Grufferman S, Ruymann F, Ognjanovic S, et al.: Prenatal X-ray exposure and rhabdomyosarcoma in children: a report from the children's oncology group. Cancer Epidemiol Biomarkers Prev 18 (4): 1271-6, 2009.[PUBMED Abstract]

Barr FG, Smith LM, Lynch JC, et al.: Examination of gene fusion status in archival samples of alveolar rhabdomyosarcoma entered on the Intergroup Rhabdomyosarcoma Study-III trial: a report from the Children's Oncology Group. J Mol Diagn 8 (2): 202-8, 2006.[PUBMED Abstract]

Heyn R, Newton WA, Raney RB, et al.: Preservation of the bladder in patients with rhabdomyosarcoma. J Clin Oncol 15 (1): 69-75, 1997.[PUBMED Abstract]

Andrassy RJ, Corpron CA, Hays D, et al.: Extremity sarcomas: an analysis of prognostic factors from the Intergroup Rhabdomyosarcoma Study III. J Pediatr Surg 31 (1): 191-6, 1996.[PUBMED Abstract]

Andrassy RJ, Hays DM, Raney RB, et al.: Conservative surgical management of vaginal and vulvar pediatric rhabdomyosarcoma: a report from the Intergroup Rhabdomyosarcoma Study III. J Pediatr Surg 30 (7): 1034-6; discussion 1036-7, 1995.[PUBMED Abstract]

Crist W, Gehan EA, Ragab AH, et al.: The Third Intergroup Rhabdomyosarcoma Study. J Clin Oncol 13 (3): 610-30, 1995.[PUBMED Abstract]

Heyn R, Han F, Ensign L, et al.: Acute nonlymphoblastic leukemia (ANLL) in patients treated for rhabdomyosarcoma with cyclophosphamide (CPM) and etoposide (VP 16) on Intergroup Rhabdomyosarcoma Study (IRS) III. [Abstract] Proceedings of the American Society of Clinical Oncology 12: A-1447, 421, 1993.

Pappo AS, Crist WM, Kuttesch J, et al.: Tumor-cell DNA content predicts outcome in children and adolescents with clinical group III embryonal rhabdomyosarcoma. The Intergroup Rhabdomyosarcoma Study Committee of the Children's Cancer Group and the Pediatric Oncology Group. J Clin Oncol 11 (10): 1901-5, 1993.[PUBMED Abstract]

Pappo AS, Crist WM, Newton W, et al.: Tumor cell DNA content predicts outcome in children and adolescents with clinical group III embryonal rhabdomyosarcoma (RMS). [Abstract] Proceedings of the American Society of Clinical Oncology 12: A-1409, 411, 1993.

Ragab A, Gehan E, Maurer H, et al.: Intergroup Rhabdomyosarcoma Study (IRS) III: preliminary report of the major results. [Abstract] Proceedings of the American Society of Clinical Oncology 11: A-1251, 1992.

Hays D, Raney R, Crist W, et al.: Improved survival and bladder preservation among patients with bladder/prostate primary tumors in Intergroup Rhabdomyosarcoma Study III (IRS). [Abstract] Proceedings of the American Society of Clinical Oncology 10: A-1119, 318, 1991.

Raney B, Crist W, Ragab A, et al.: Results of intensive treatment of children with advanced soft-tissue sarcoma (STS): an Intergroup Rhabdomyosarcoma Study (IRS)-III pilot program. [Abstract] Proceedings of the American Society of Clinical Oncology 4: C-957, 246, 1985.

Related Publications

Raney B, Huh W, Hawkins D, et al.: Outcome of patients with localized orbital sarcoma who relapsed following treatment on Intergroup Rhabdomyosarcoma Study Group (IRSG) Protocols-III and -IV, 1984-1997: a report from the Children's Oncology Group. Pediatr Blood Cancer 60 (3): 371-6, 2013.[PUBMED Abstract]

La TH, Wolden SL, Rodeberg DA, et al.: Regional nodal involvement and patterns of spread along in-transit pathways in children with rhabdomyosarcoma of the extremity: a report from the Children's Oncology Group. Int J Radiat Oncol Biol Phys 80 (4): 1151-7, 2011.[PUBMED Abstract]

La TH, Wolden SL, Su Z, et al.: Local therapy for rhabdomyosarcoma of the hands and feet: is amputation necessary? A report from the Children's Oncology Group. Int J Radiat Oncol Biol Phys 80 (1): 206-12, 2011.[PUBMED Abstract]

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]

Pressey JG, Anderson JR, Crossman DK, et al.: Hedgehog pathway activity in pediatric embryonal rhabdomyosarcoma and undifferentiated sarcoma: a report from the Children's Oncology Group. Pediatr Blood Cancer 57 (6): 930-8, 2011.[PUBMED Abstract]

Raney RB, Anderson JR, Brown KL, et al.: Treatment results for patients with localized, completely resected (Group I) alveolar rhabdomyosarcoma on Intergroup Rhabdomyosarcoma Study Group (IRSG) protocols III and IV, 1984-1997: a report from the Children's Oncology Group. Pediatr Blood Cancer 55 (4): 612-6, 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, Chintagumpala M, Anderson J, et al.: Results of treatment of patients with superficial facial rhabdomyosarcomas on protocols of the Intergroup Rhabdomyosarcoma Study Group (IRSG), 1984-1997. Pediatr Blood Cancer 50 (5): 958-64, 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.

Pappo AS, Anderson JR, Crist WM, et al.: Survival after relapse in children and adolescents with rhabdomyosarcoma: A report from the Intergroup Rhabdomyosarcoma Study Group. J Clin Oncol 17 (11): 3487-93, 1999.[PUBMED Abstract]

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]

Pawel BR, Hamoudi AB, Asmar L, et al.: Undifferentiated sarcomas of children: pathology and clinical behavior--an Intergroup Rhabdomyosarcoma study. Med Pediatr Oncol 29 (3): 170-80, 1997.[PUBMED Abstract]

Corpron CA, Andrassy RJ, Hays DM, et al.: Conservative management of uterine pediatric rhabdomyosarcoma: a report from the Intergroup Rhabdomyosarcoma Study III and IV pilot. J Pediatr Surg 30 (7): 942-4, 1995.[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.

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]

Hays DM, Lawrence W Jr, Crist WM, et al.: Partial cystectomy in the management of rhabdomyosarcoma of the bladder: a report from the Intergroup Rhabdomyosarcoma Study. J Pediatr Surg 25 (7): 719-23, 1990.[PUBMED Abstract]

Crist WM, Raney RB, Ragab A, et al.: Intensive chemotherapy including cisplatin with or without etoposide for children with soft-tissue sarcomas. Med Pediatr Oncol 15 (2): 51-7, 1987.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Soft Tissue Sarcoma Committee

Harold Maurer, MD, Protocol chair
Ph: 402-559-4200

Pediatric Oncology Group

Harold Maurer, MD, Protocol chair
Ph: 402-559-4200

Children's Cancer Group

R. Beverly Raney, MD, Protocol chair (Contact information may not be current)
Ph: 512-420-8180; 800-392-1611

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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