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

Sarcoma Clinical Trial

Official title:

Localized Non-Rhabdomyosarcoma Soft Tissue Sarcomas

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00334854
• Other study ID #: CCLG-EPSSG-NRSTS-2005
• Secondary ID: CDR0000482277EU-
• Status: Recruiting
• Phase: Phase 3
• First received: June 7, 2006
• Last updated: August 9, 2013
• Start date: March 2006

Study information

• Verified date: July 2009
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Unspecified
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 250
• Est. primary completion date: May 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 20 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Childhood Malignant Fibrous Histiocytoma of Bone
• Histiocytoma
• Histiocytoma, Malignant Fibrous
• Sarcoma

Intervention

Drug:
• doxorubicin hydrochloride

• ifosfamide

Procedure:
• adjuvant therapy

• conventional surgery

• neoadjuvant therapy

Radiation:
• radiation therapy

Locations

Country	Name	City	State
Austria	St. Anna Children's Hospital	Vienna
Belgium	Clinique de l'Esperance	Montegnee
Denmark	Rigshospitalet - Copenhagen University Hospital	Copenhagen
France	Institut Curie Hopital	Paris
Ireland	Our Lady's Hospital for Sick Children Crumlin	Dublin
Spain	Vall d'Hebron University Hospital	Barcelona
Sweden	Uppsala University Hospital	Uppsala
Switzerland	University Children's Hospital	Zurich
United Kingdom	Royal Aberdeen Children's Hospital	Aberdeen	Scotland
United Kingdom	Royal Belfast Hospital for Sick Children	Belfast	Northern Ireland
United Kingdom	Birmingham Children's Hospital	Birmingham	England
United Kingdom	Institute of Child Health at University of Bristol	Bristol	England
United Kingdom	Addenbrooke's Hospital	Cambridge	England
United Kingdom	Childrens Hospital for Wales	Cardiff	Wales
United Kingdom	Royal Hospital for Sick Children	Edinburgh	Scotland
United Kingdom	Royal Hospital for Sick Children	Glasgow	Scotland
United Kingdom	Leeds Cancer Centre at St. James's University Hospital	Leeds	England
United Kingdom	Leicester Royal Infirmary	Leicester	England
United Kingdom	Royal Liverpool Children's Hospital, Alder Hey	Liverpool	England
United Kingdom	Great Ormond Street Hospital for Children	London	England
United Kingdom	Middlesex Hospital	London	England
United Kingdom	Royal Manchester Children's Hospital	Manchester	England
United Kingdom	Sir James Spence Institute of Child Health at Royal Victoria Infirmary	Newcastle-Upon-Tyne	England
United Kingdom	Queen's Medical Centre	Nottingham	England
United Kingdom	Oxford Radcliffe Hospital	Oxford	England
United Kingdom	Children's Hospital - Sheffield	Sheffield	England
United Kingdom	Southampton General Hospital	Southampton	England
United Kingdom	Royal Marsden - Surrey	Sutton	England

Sponsors (5)

Lead Sponsor	Collaborator
European Paediatric Soft Tissue Sarcoma Study Group	Children's Cancer and Leukaemia Group, Cooperative Weichteilsarkom Studie, Dutch Childhood Oncology Group, Italian Association for Pediatric Hematology Oncology

Countries where clinical trial is conducted

Austria,  Belgium,  Denmark,  France,  Ireland,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-free survival			No
Primary	Local relapse-free survival			No
Primary	Metastases-free survival			No
Primary	Overall survival			No
Primary	Response rate (complete response, very good partial response [PR], PR, minor PR, and stable disease)			No