Trial | NCT00334854  Report issue

Title

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

  • Phase

    Phase 3

  • Study Type

    Interventional

  • Status

    Unknown status

  • Intervention/Treatment

    doxorubicin ifosfamide ...

  • Study Participants

    250
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.
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.
Study Started
Mar 31
2006
Primary Completion
May 31
2010
Anticipated
Last Update
Aug 12
2013
Estimate

Drug doxorubicin hydrochloride

Drug ifosfamide

Procedure adjuvant therapy

Procedure conventional surgery

Procedure neoadjuvant therapy

Radiation radiation therapy

Criteria 

DISEASE CHARACTERISTICS:

Histologically confirmed synovial sarcoma or adult-type soft-tissue sarcoma

Adult-type soft tissue sarcoma includes any of the following:

Fibrosarcoma (adult-type)

No infantile fibrosarcoma

Malignant peripheral nerve sheath tumor

Malignant schwannoma
Neurofibrosarcoma
Epithelioid sarcoma
Leiomyosarcoma
Clear cell sarcoma
Liposarcoma
Alveolar soft-part sarcoma
Malignant fibrous histiocytoma
Hemangiopericytoma
Angiosarcoma
Dermatofibrosarcoma protuberans
Mesenchymal chondrosarcoma
No borderline tumors (e.g., hemangioendothelioma)
No small round cell tumors (e.g., extraosseous Ewing's sarcoma/primitive neuroectodermal tumor or desmoplastic small round cell tumor)
Post-irradiation soft-part sarcomas allowed
Diagnostic surgery performed within the past 8 weeks (for patients who require adjuvant chemotherapy)

No evidence of metastatic disease

Involved locoregional lymph nodes are allowed

PATIENT CHARACTERISTICS:

No prior malignancy
No pre-existing illness precluding study treatment*
Normal renal function (nephrotoxicity grade 0-1)*
No history of cardiac disease*
Normal shortening fraction (> 28%)*
Ejection fraction > 47%* NOTE: * For patients who require adjuvant chemotherapy

PRIOR CONCURRENT THERAPY:

No prior cancer treatment except primary surgery
No Results Posted