RATIONALE: Drugs used in chemotherapy, such as ifosfamide and doxorubicin, work in different
      ways to stop the growth of tumor cells, either by killing the cells or by stopping them from
      dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.
      Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination
      chemotherapy with or without radiation therapy before surgery may make the tumor smaller and
      reduce the amount of normal tissue that needs to be removed. Giving radiation therapy after
      surgery may kill any tumor cells that remain after surgery.

      PURPOSE: This phase III trial is studying how well giving ifosfamide and doxorubicin,
      radiation therapy, and/or surgery works in treating young patients with localized soft tissue
      sarcoma.

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

Childhood Malignant Fibrous Histiocytoma of Bone

Sarcoma

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.

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

About this trial

Study ID

Status

Type

Phase

Placebo

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Trial Timing

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