Ifosfamide and Doxorubicin, Radiation Therapy, and/or Surgery in Treating Young Patients With Localized Soft Tissue Sarcoma

• Event-free survival [ Designated as safety issue: No ]
  
• Local relapse-free survival [ Designated as safety issue: No ]
  
• Metastases-free survival [ Designated as safety issue: No ]
  
• Overall survival [ Designated as safety issue: No ]
  
• Response rate (complete response, very good partial response [PR], PR, minor PR, and stable disease) [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Determine survival rates (event-free survival and overall survival [OS]) and the pattern of treatment failure in patients with synovial sarcoma or adult-type soft tissue sarcoma treated with ifosfamide and doxorubicin hydrochloride, radiotherapy, and/or surgery.
• Determine the role of ifosfamide and doxorubicin hydrochloride in improving the response rate in patients with unresectable synovial sarcoma or adult-type soft tissue sarcoma.

Secondary

• Evaluate clinical/pathological prognostic factors, particularly tumor grade and radiological and pathological response to neoadjuvant treatment.
• Determine the impact of omitting adjuvant chemotherapy in patients with low-risk synovial sarcoma (tumor < 5 cm).
• Determine the role of adjuvant chemotherapy in improving the metastases-free survival and OS in patients with adult-type soft tissue sarcoma (Intergroup Rhabdomyosarcoma Study [IRS] postsurgical grouping system I-II, tumor grade 3, tumor size > 5 cm).

OUTLINE: This is a nonrandomized, prospective, historically controlled, multicenter study. Patients with synovial sarcoma are stratified according to the Intergroup Rhabdomyosarcoma Study (IRS) postsurgical grouping system (I vs II vs III) and tumor size ( ≤ 5 cm vs > 5 cm). Patients with adult-type soft tissue sarcoma are stratified according to the IRS postsurgical grouping system (I vs II vs III), tumor size ( ≤ 5 cm vs > 5 cm), and tumor grade (G1 vs G2 vs G3). Patients are assigned to 1 of 9 treatment groups according to disease and stratification.

Synovial sarcoma

• Group 1 (IRS group I, tumor ≤ 5 cm): Patients undergo surgical resection of tumor.
• Group 2 (IRS group I, tumor > 5 cm): Patients receive ifosfamide IV over 3 hours on days 1-3 and doxorubicin hydrochloride IV over 4-6 hours on days 1 and 2 (IFO-DOX). Treatment repeats every 21 days for 4 courses.
• Group 3 (IRS group II, tumor ≤ 5 cm): Patients receive 3 courses of IFO-DOX. After the completion of chemotherapy, patients undergo radiotherapy 5 days a week for 5-6 weeks.
• Group 4 (IRS group II, tumor > 5 cm): Patients receive 3 courses of IFO-DOX. Patients then receive ifosfamide alone IV over 3 hours on days 1-3. Treatment with ifosfamide repeats every 21 days for 2 courses. Patients also receive concurrent radiotherapy (concurrently with ifosfamide) 5 days a week for 5-6 weeks. After completion of radiotherapy, patients receive 1 additional course of IFO-DOX.

• Group 5 (IRS group III, N1): Patients receive 3 courses of IFO-DOX. Patients with no response to chemotherapy receive 1 of the following local therapies:

  • Delayed complete resection*
  • Radiotherapy (as in group 3) followed by surgery*
  • Delayed complete resection* followed by radiotherapy** (as in group 3)
  • Delayed incomplete resection* followed by radiotherapy** (as in group 3)
  • Radiotherapy (as in group 3) Patients with major or minor response to chemotherapy receive 2 courses of ifosfamide with concurrent radiotherapy followed by 1 additional course of IFO-DOX (as in group 4, above).

NOTE: * Patients undergo surgery 5 weeks after completion of chemotherapy and/or radiotherapy.

NOTE: **Patients undergo radiotherapy beginning < 21 days after surgery.

Adult-type soft tissue sarcoma

• Group 1 (IRS group I, tumor ≤ 5 cm): Patients undergo surgical resection of tumor.

• Group 2 (IRS group I, tumor > 5 cm): Patients receive therapy according to tumor grade:

  • G1 disease: Patients undergo surgical resection.
  • G2 disease: Patients undergo radiotherapy 5 days a week for 5-6 weeks.
  • G3 disease: Patients receive the following sequential treatment: 3 courses of IFO-DOX followed by 2 courses of ifosfamide with concurrent radiotherapy followed by 1 course of IFO-DOX.

• Group 3 (IRS group II, N0): Patients receive therapy according to tumor grade:

  • G1 disease: Patients undergo surgical resection.
  • G2-3 disease (≤ 5 cm) and G2 disease (> 5 cm): Patients undergo radiotherapy 5 days a week for 5-6 weeks.
  • G3 disease (> 5 cm): Patients undergo sequential treatment (as in group 2, adult-type soft tissue sarcoma).
• Group 4 (IRS group III, N1): Patients receive 3 courses of IFO-DOX. Patients with no response to chemotherapy receive local therapy (as in group 5 synovial sarcoma). Patients with major or minor response to chemotherapy receive 2 courses of ifosfamide with concurrent radiotherapy followed by 2 additional courses of IFO-DOX (as in group 4, synovial sarcoma).

After completion of study therapy, patients are followed periodically for up to 10 years.

PROJECTED ACCRUAL: A total of 250 patients will be accrued for this study.