Phase II Pilot Combination Chemotherapy Including IPP/ADR plus Hyperfractionated Radiotherapy in Children with Clinical Group IV Rhabdomyosarcoma
Basic Trial Information
|Phase II||Treatment||Completed||under 21||NCI||IRS-IV-P-GROUP4|
CCG-6881, POG-8889, INT-0092
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.
See General Eligibility Criteria
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).
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.
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.
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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]
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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]
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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]
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Trial Contact Information
Trial Lead Organizations
Soft Tissue Sarcoma Committee
Pediatric Oncology Group
Children's Cancer Group
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.