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

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

250 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-03-31

Brief Summary

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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

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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

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Childhood Malignant Fibrous Histiocytoma of Bone Sarcoma

Keywords

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childhood synovial sarcoma nonmetastatic childhood soft tissue sarcoma childhood alveolar soft-part sarcoma childhood angiosarcoma childhood epithelioid sarcoma childhood fibrosarcoma childhood leiomyosarcoma childhood liposarcoma childhood neurofibrosarcoma localized childhood malignant fibrous histiocytoma of bone childhood malignant hemangiopericytoma dermatofibrosarcoma protuberans chondrosarcoma

Study Design

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Allocation Method

NON_RANDOMIZED

Primary Study Purpose

TREATMENT

Interventions

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doxorubicin hydrochloride

Intervention Type DRUG

ifosfamide

Intervention Type DRUG

adjuvant therapy

Intervention Type PROCEDURE

conventional surgery

Intervention Type PROCEDURE

neoadjuvant therapy

Intervention Type PROCEDURE

radiation therapy

Intervention Type RADIATION

Eligibility Criteria

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Inclusion 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

Maximum Eligible Age

20 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Principal Investigators

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Andrea Ferrari, MD

Role: STUDY_CHAIR

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Modesto Carli, MD

Role: STUDY_CHAIR

Azienda Ospedaliera di Padova

Joern Treuner, MD

Role: STUDY_CHAIR

Olgahospital

Bernadette Brennan, MD

Role: STUDY_CHAIR

Royal Manchester Children's Hospital

Max Van Noesel, MD, PhD

Role: STUDY_CHAIR

Erasmus MC-Sophia Children's Hospital

Locations

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St. Anna Children's Hospital

Vienna, , Austria

Site Status RECRUITING

Clinique de l'Esperance

Montegnée, , Belgium

Site Status RECRUITING

Rigshospitalet - Copenhagen University Hospital

Copenhagen, , Denmark

Site Status RECRUITING

Institut Curie Hopital

Paris, , France

Site Status RECRUITING

Our Lady's Hospital for Sick Children Crumlin

Dublin, , Ireland

Site Status RECRUITING

Vall d'Hebron University Hospital

Barcelona, , Spain

Site Status RECRUITING

Uppsala University Hospital

Uppsala, , Sweden

Site Status RECRUITING

University Children's Hospital

Zurich, , Switzerland

Site Status RECRUITING

Birmingham Children's Hospital

Birmingham, England, United Kingdom

Site Status RECRUITING

Institute of Child Health at University of Bristol

Bristol, England, United Kingdom

Site Status RECRUITING

Addenbrooke's Hospital

Cambridge, England, United Kingdom

Site Status RECRUITING

Leeds Cancer Centre at St. James's University Hospital

Leeds, England, United Kingdom

Site Status RECRUITING

Leicester Royal Infirmary

Leicester, England, United Kingdom

Site Status RECRUITING

Royal Liverpool Children's Hospital, Alder Hey

Liverpool, England, United Kingdom

Site Status RECRUITING

Middlesex Hospital

London, England, United Kingdom

Site Status RECRUITING

Great Ormond Street Hospital for Children

London, England, United Kingdom

Site Status RECRUITING

Royal Manchester Children's Hospital

Manchester, England, United Kingdom

Site Status RECRUITING

Sir James Spence Institute of Child Health at Royal Victoria Infirmary

Newcastle upon Tyne, England, United Kingdom

Site Status RECRUITING

Queen's Medical Centre

Nottingham, England, United Kingdom

Site Status RECRUITING

Oxford Radcliffe Hospital

Oxford, England, United Kingdom

Site Status RECRUITING

Children's Hospital - Sheffield

Sheffield, England, United Kingdom

Site Status RECRUITING

Southampton General Hospital

Southampton, England, United Kingdom

Site Status RECRUITING

Royal Marsden - Surrey

Sutton, England, United Kingdom

Site Status RECRUITING

Royal Belfast Hospital for Sick Children

Belfast, Northern Ireland, United Kingdom

Site Status RECRUITING

Royal Aberdeen Children's Hospital

Aberdeen, Scotland, United Kingdom

Site Status RECRUITING

Royal Hospital for Sick Children

Edinburgh, Scotland, United Kingdom

Site Status RECRUITING

Royal Hospital for Sick Children

Glasgow, Scotland, United Kingdom

Site Status RECRUITING

Childrens Hospital for Wales

Cardiff, Wales, United Kingdom

Site Status RECRUITING

Countries

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Germany Austria Belgium Denmark France Ireland Spain Sweden Switzerland United Kingdom

Facility Contacts

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Ruth Ladenstein, MD

Role: primary

Nadine Francotte, MD

Role: primary

Catherine Rechnitzer, MD, PhD

Role: primary

Daniel Orbach, MD

Role: primary

Anne O'Meara, MD

Role: primary

Soledad Gallego, MD, PhD

Role: primary

Gustaf Ljungman, MD

Role: primary

Felix Niggli, MD

Role: primary

David Hobin, MD

Role: primary

M. C. G. Stevens, MD

Role: primary

Denise Williams, MD

Role: primary

Adam Glaser, MD

Role: primary

Johann Visser, MD

Role: primary

Heather P. McDowell, MD

Role: primary

Ananth Shankar, MD

Role: primary

Julia Chisholm, MD

Role: primary

Bernadette Brennan, MD

Role: primary

Juliet Hale, MD

Role: primary

Martin Hewitt, MD, BSc, FRCP, FRCPCH

Role: primary

Kate Wheeler, MD

Role: primary

Mary P. Gerrard, MBChB, FRCP, FRCPCH

Role: primary

Janice A. Kohler, MD, FRCP

Role: primary

Kathy Pritchard-Jones, MD

Role: primary

Anthony McCarthy, MD

Role: primary

Derek King, MD

Role: primary

W. Hamish Wallace, MD

Role: primary

Milind D. Ronghe, MD

Role: primary

Heidi Traunecker, MD, PhD

Role: primary