NCT00334854

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

Localized Non-Rhabdomyosarcoma Soft Tissue Sarcomas

• Status: Unknown
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 250 (estimated)
• Sponsor: European Paediatric Soft Tissue Sarcoma Study Group · Academic / Other
• Sex: All
• Age: 20 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Childhood Malignant Fibrous Histiocytoma of Bone
• Sarcoma

Interventions

Type	Name	Description
DRUG	doxorubicin hydrochloride
DRUG	ifosfamide
PROCEDURE	adjuvant therapy
PROCEDURE	conventional surgery
PROCEDURE	neoadjuvant therapy
RADIATION	radiation therapy

Timeline

• Start date: 2006-03-01
• Primary completion: 2010-05-01
• First posted: 2006-06-08
• Last updated: 2013-08-12

Locations

28 sites across 9 countries: Austria, Belgium, Denmark, France, Ireland, Spain, Sweden, Switzerland, United Kingdom