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

Basic Trial Information

Objectives

I.  Determine the feasibility of and toxicity associated with 
ifosfamide/doxorubicin as induction chemotherapy and, subsequently, as part of 
maintenance chemotherapy along with vincristine/actinomycin-D/cyclophosphamide 
in children with Clinical Group IV rhabdomyosarcoma and similar sarcomas.
II.  Determine the feasibility of and toxicity associated with a 
hyperfractionated radiotherapy regimen following induction chemotherapy in 
these patients.

Entry Criteria

Disease Characteristics:

See General Eligibility Criteria

Patient Characteristics:

See General Eligibility Criteria

General Eligibility Criteria:

Patients under the age of 21 years at 
diagnosis with pathologically documented Clinical Group IV rhabdomyosarcoma, 
undifferentiated sarcoma type indeterminate, or extraosseous Ewing's sarcoma, 
provided they have received no prior chemotherapy (steroids excepted) or 
radiotherapy.  Patients must be registered on study and begun on protocol 
treatment within 21 days of the final surgical procedure or within 42 days of 
the initial surgical procedure (e.g., biopsy).

Expected Enrollment

About 36 patients will be entered into the pilot study over about 12 months.  
It is anticipated that following completion of the pilot study, ID 
chemotherapy will be incorporated into a 3-arm open randomized study and 
hyperfractionated radiotherapy will be incorporated into a 2-arm randomized 
radiation study.

Outline

Nonrandomized study.  All patients receive Induction therapy on Regimen F 
Induction, and responders are treated on Regimen F Continuation.  Patients who 
do not respond to ifosfamide/doxorubicin receive Continuation therapy on 
Regimen G.  Patients with cranial parameningeal sarcoma (primary sites in the 
nasopharynx, nasal cavity, paranasal sinuses, middle ear-mastoid, 
pterygopalatine and infratemporal fossae) receive specialized treatment on 
Regimen I, II, or III, as appropriate, concomitantly with Induction 
chemotherapy:  patients with tumors that extend intracranially from the 
primary site as determined by MRI or CT are treated on Regimen I; those with 
tumors causing base of skull erosion and/or cranial nerve palsy but not 
extending intracranially from the primary site as determined by MRI or CT are 
treated on Regimen II; and those with tumors that do not extend into the 
cranial cavity or cause base of skull erosion and/or cranial nerve palsy as 
determined by MRI or CT are treated on Regimen III.
Regimen F Induction:  2-Drug Combination Chemotherapy plus Urothelial 
Protection followed by 3-Drug Combination Chemotherapy plus Urothelial 
Protection plus Radiotherapy.  ID:  Ifosfamide, IPP, NSC-109724; Doxorubicin, 
Adriamycin, ADR, NSC-123127; plus Mercaptoethane sulfonate, Mesna, NSC-113891; 
followed by VAC:  Vincristine, VCR, NSC-67574; Actinomycin-D, ACT-D, NSC-3053; 
Cyclophosphamide, CTX, NSC-26271; plus Mesna; plus involved field irradiation 
using Co60 equipment or linear accelerators with beam energies of 4-10 MeV.
Regimen F Continuation:  3-Drug Combination Chemotherapy plus Urothelial 
Protection Alternating with 3-Drug Combination Chemotherapy plus Urothelial 
Protection and Followed by 3-Drug Combination Chemotherapy plus Urothelial 
Protection.  VID:  VCR; IPP; ADR; plus Mesna; alternating with VAC plus Mesna 
and followed by VAC plus Mesna.
Regimen G Continuation.  3-Drug Combination Chemotherapy plus Urothelial 
Protection.  VAC; plus Mesna.
Regimen I:  3-Drug Combination Intrathecal Chemotherapy plus Leucovorin Rescue 
plus Radiotherapy.  Triple Intrathecal Therapy, TIT:  Methotrexate, MTX, 
NSC-740; Hydrocortisone, HC, NSC-10483; Cytosine arabinoside, ARA-C, 
NSC-63878; plus Leucovorin calcium, Citrovorum Factor, CF, NSC-3590; plus 
irradiation of the primary tumor site plus whole-brain irradiation plus (as 
indicated) irradiation of entire spinal meninges beginning on day 0.
Regimen II:  3-Drug Combination Intrathecal Chemotherapy plus Leucovorin 
Rescue plus Radiotherapy.  TIT; plus CF; plus irradiation of primary tumor 
with limited margin beginning on day 0.
Regimen III:  Radiotherapy.  Irradiation of the primary site plus a limited 
margin beginning on week 18.5.

Sandler E, Lyden E, Ruymann F, et al.: Efficacy of ifosfamide and doxorubicin given as a phase II "window" in children with newly diagnosed metastatic rhabdomyosarcoma: a report from the Intergroup Rhabdomyosarcoma Study Group. Med Pediatr Oncol 37 (5): 442-8, 2001.[PUBMED Abstract]

Raney RB, Crist WM, Donaldson SS, et al.: A pilot study of ifosfamide/MESNA and doxorubicin (IFOS/DOX) followed by vincristine, actinomycin D, cyclophosphamide (VAC) and hyperfractionated irradiation (HFRT) for children with metastatic soft-tissue sarcoma: a report from the Intergroup Rhabdomyosarcoma Study. [Abstract] Proceedings of the American Society of Clinical Oncology 10: A-1098, 1991.

Lager JJ, Lyden ER, Anderson JR, et al.: Pooled analysis of phase II window studies in children with contemporary high-risk metastatic rhabdomyosarcoma: a report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group. J Clin Oncol 24 (21): 3415-22, 2006.[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]

Arndt C, Tefft M, Gehan E, et al.: A feasibility, toxicity, and early response study of etoposide, ifosfamide, and vincristine for the treatment of children with rhabdomyosarcoma: a report from the Intergroup Rhabdomyosarcoma Study (IRS) IV pilot study. J Pediatr Hematol Oncol 19 (2): 124-9, 1997 Mar-Apr.[PUBMED Abstract]

Donaldson SS, Asmar L, Breneman J, et al.: Hyperfractionated radiation in children with rhabdomyosarcoma--results of an Intergroup Rhabdomyosarcoma Pilot Study. Int J Radiat Oncol Biol Phys 32 (4): 903-11, 1995.[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]

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]

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.

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]

Raney B, Ensign LG, Foreman J, et al.: Renal toxicity of ifosfamide in pilot regimens of the intergroup rhabdomyosarcoma study for patients with gross residual tumor. Am J Pediatr Hematol Oncol 16 (4): 286-95, 1994.[PUBMED Abstract]

Raney B, Ensign L, Foreman J, et al.: Renal toxicity in patients receiving ifosfamide/mesna on Intergroup Rhabdomyosarcoma Study (IRS)-IV pilot regimens for gross residual sarcoma. [Abstract] Proceedings of the American Society of Clinical Oncology 12: A-1435, 418, 1993.

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

Jorge Ortega, MD, Protocol chair		Ph: 213-669-2163 Email: jortega@chlais.usc.edu

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