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Clinical Trials (PDQ®)

IRS Study IV: Phase III Comparison of VAC (VCR/DACT/CTX) vs VAI (VCR/DACT/IFF) vs VIE (VCR/IFF/VP-16) in Patients with Stage 1 Rhabdomyosarcoma

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

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IIITreatmentClosedunder 21 at diagnosisNCIIRS-IV-STAGE-1
CCG-6901, POG-9150, INT-0117, IRS-IV

Objectives

I.  Compare, in a phase III setting, progression-free survival of patients 
with stage 1 rhabdomyosarcoma and undifferentiated sarcoma randomly assigned 
to treatment with vincristine/dactinomycin/cyclophosphamide (VAC) vs. 
vincristine/dactinomycin/ifosfamide (VAI) vs. vincristine/ifosfamide/etoposide 
(VIE).

II.  Compare hyperfractionated irradiation vs. conventional radiotherapy with 
regard to local relapse rates and acute and late toxicity.

III.  Investigate the relationship between immunohistochemical patterns of 
tumor and prognosis, and evaluate newly identified immunohistochemical markers 
in diagnosis.

IV.  Correlate clinical features of disease and prognosis with tumor 
cytogenetics, DNA labeling index, and amplification or rearrangement of 
specific cellular proto-oncogenes.

V.  Provide a bank of frozen tumor tissue for use in tumor biology studies.

VI.  Evaluate recombinant granulocyte colony-stimulating factor as a 
supportive measure for amelioration of hematopoietic toxicity.

Entry Criteria

Disease Characteristics:


Pathologically documented rhabdomyosarcoma or undifferentiated
sarcoma, type indeterminate
 Stage 1 disease eligible if have intermediate risk features
  Group II, N1
  Group III, N0 other than orbit/eyelid primaries
  Group III, N1, all primary sites
  No metastatic disease (i.e., not Group IV)

Primary brain and spinal cord rhabdomyosarcoma excluded



Prior/Concurrent Therapy:


Biologic therapy:
  Not specified

Chemotherapy:
  No prior chemotherapy

Endocrine therapy:
  Prior steroid therapy allowed

Radiotherapy:
  No prior radiotherapy

Surgery:
  Treatment must begin within 42 days of the surgical procedure (e.g., biopsy)
  that produced the definitive diagnosis


Patient Characteristics:


Age:
  Under 21 at diagnosis

Performance status:
  Not specified

Hematopoietic:
  Not specified

Hepatic:
  Not specified

Renal:
  Creatinine normal for age if randomized

Other:
  Patients who qualify are registered on companion protocol
  CCG-B904/POG-9153/NCI-INT-0120 (tumor biology protocol)


Expected Enrollment

It is estimated that 39 patients with Stage 1 disease (exclusive of those with 
paratesticular and Groups I and II orbit/eyelid tumors) will be entered per 
year and that 4.7 years of accrual will be necessary.  It is estimated that 9 
paratesticular patients, less than 1 Clinical Group I orbit/eyelid patient, 
and 4 Clinical Group II orbit/eyelid patients will be entered per year.

Outline

Randomized study.  Patients will have undergone excision of as much gross 
tumor as possible prior to entry.  All patients except those with Clinical 
Group I paratesticular lesions and Clinical Groups I and II orbit/eyelid 
lesions are randomized on Arms I, II, and III.  Patients with Clinical Group I 
paratesticular and orbit/eyelid lesions are nonrandomly assigned to Regimen A, 
and Clinical Group II orbit/eyelid patients are nonrandomly assigned to 
Regimen A with conventional radiotherapy.  Clinical Group III patients (except 
those with vulvar/vaginal primaries) are randomized for hyperfractionated vs. 
conventional radiotherapy on Arms IV and V; Clinical Group II patients and 
Group III patients with vulvar/vaginal primaries are nonrandomly assigned to 
Arm V for conventional radiotherapy.  Clinical Group I patients do not receive 
radiotherapy.

Arm I:  3-Drug Combination Chemotherapy with Urothelial Protection and 
Hematopoietic Stimulation.  VAC (Regimens 40 and 41):  Vincristine, VCR, 
NSC-67574; Dactinomycin, DACT, NSC-3053; Cyclophosphamide, CTX, NSC-26271; 
with Mesna, NSC-113891; and Granulocyte Colony-Stimulating Factor (Amgen); 
G-CSF; NSC-614629.

Arm II:  3-Drug Combination Chemotherapy with Urothelial Protection and 
Hematopoietic Stimulation.  VAI (Regimen 42):  VCR; DACT; Ifosfamide, IFF, 
NSC-109724; with Mesna; and G-CSF.  (VAC replaces VAI for the last 2 
continuation courses.)

Arm III:  3-Drug Combination Chemotherapy with Urothelial Protection and 
Hematopoietic Stimulation.  VIE (Regimen 43):  VCR; IFF; Etoposide, VP-16, 
NSC-141540; with Mesna; and G-CSF.  (VAC replaces VIE for the last 2 
continuation courses.)

Regimen A:  2-Drug Combination Chemotherapy with Hematopoietic Stimulation.  
Regimen 44:  DACT; VCR; with G-CSF.

Arm IV:  Radiotherapy.  Involved-field irradiation using Co60 equipment or 
linear accelerators with minimum beam energies of 4-20 MV (electrons and 
brachytherapy may be appropriate in certain situations).  Hyperfractionated 
schedule.

Arm V:  Radiotherapy.  Involved-field irradiation as in Arm IV.  Conventional 
schedule.

Published Results

Gupta AA, Anderson JR, Pappo AS, et al.: Patterns of chemotherapy-induced toxicities in younger children and adolescents with rhabdomyosarcoma: a report from the Children's Oncology Group Soft Tissue Sarcoma Committee. Cancer 118 (4): 1130-7, 2012.[PUBMED Abstract]

Rodeberg DA, Garcia-Henriquez N, Lyden ER, et al.: Prognostic significance and tumor biology of regional lymph node disease in patients with rhabdomyosarcoma: a report from the Children's Oncology Group. J Clin Oncol 29 (10): 1304-11, 2011.[PUBMED Abstract]

Raney B, Stoner J, Anderson J, et al.: Impact of tumor viability at second-look procedures performed before completing treatment on the Intergroup Rhabdomyosarcoma Study Group protocol IRS-IV, 1991-1997: a report from the children's oncology group. J Pediatr Surg 45 (11): 2160-8, 2010.[PUBMED Abstract]

Arndt C, Rodeberg D, Breitfeld PP, et al.: Does bladder preservation (as a surgical principle) lead to retaining bladder function in bladder/prostate rhabdomyosarcoma? Results from intergroup rhabdomyosarcoma study iv. J Urol 171 (6 Pt 1): 2396-403, 2004.[PUBMED Abstract]

Crist WM, Anderson JR, Meza JL, et al.: Intergroup rhabdomyosarcoma study-IV: results for patients with nonmetastatic disease. J Clin Oncol 19 (12): 3091-102, 2001.[PUBMED Abstract]

Crist W, Anderson J, Maurer H, et al.: Preliminary results for patients with local/regional tumors treated on the Intergroup Rhabdomyosarcoma Study-IV (1991-1997). [Abstract] Proceedings of the American Society of Clinical Oncology 18: 2141A, 555a, 1999.

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]

Ortega JA, Donaldson S, Ivy SP, et al.: Venocclusive disease (VOD) of the liver following vincristine-actinomycin D-cyclophosphamide (VAC) therapy for rhabdomyosarcoma (RMS): a report from the Intergroup Rhabdomyosarcoma Study (IRS) group. [Abstract] Proceedings of the American Society of Clinical Oncology 14: A-1401, 440, 1995.

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]

Malempati S, Rodeberg DA, Donaldson SS, et al.: Rhabdomyosarcoma in infants younger than 1 year: a report from the Children's Oncology Group. Cancer 117 (15): 3493-501, 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]

Davicioni E, Anderson JR, Buckley JD, et al.: Gene expression profiling for survival prediction in pediatric rhabdomyosarcomas: a report from the children's oncology group. J Clin Oncol 28 (7): 1240-6, 2010.[PUBMED Abstract]

Minn AY, Lyden ER, Anderson JR, et al.: Early treatment failure in intermediate-risk rhabdomyosarcoma: results from IRS-IV and D9803--a report from the Children's Oncology Group. J Clin Oncol 28 (27): 4228-32, 2010.[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.

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]

Trial Contact Information

Trial Lead Organizations

Soft Tissue Sarcoma Committee

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

Pediatric Oncology Group

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

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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