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

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified July 2009 by National Cancer Institute (NCI).
Recruitment status was:  Recruiting
Sponsor:
Collaborators:
Italian Association for Pediatric Hematology Oncology
Cooperative Weichteilsarkom Studie
Children's Cancer and Leukaemia Group
Dutch Childhood Oncology Group
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00334854
First received: June 7, 2006
Last updated: August 9, 2013
Last verified: July 2009
  Purpose

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.


Condition Intervention Phase
Childhood Malignant Fibrous Histiocytoma of Bone
Sarcoma
Drug: doxorubicin hydrochloride
Drug: ifosfamide
Procedure: adjuvant therapy
Procedure: conventional surgery
Procedure: neoadjuvant therapy
Radiation: radiation therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Primary Purpose: Treatment
Official Title: Localized Non-Rhabdomyosarcoma Soft Tissue Sarcomas

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Event-free survival
  • Local relapse-free survival
  • Metastases-free survival
  • Overall survival
  • Response rate (complete response, very good partial response [PR], PR, minor PR, and stable disease)

Estimated Enrollment: 250
Study Start Date: March 2006
Estimated Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
  Hide Detailed Description

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.

  Eligibility

Ages Eligible for Study:   up to 20 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00334854

Locations
Austria
St. Anna Children's Hospital
Vienna, Austria, A-1090
Belgium
Clinique de l'Esperance
Montegnee, Belgium, 4420
Denmark
Rigshospitalet - Copenhagen University Hospital
Copenhagen, Denmark, 2100
France
Institut Curie Hopital
Paris, France, 75248
Ireland
Our Lady's Hospital for Sick Children Crumlin
Dublin, Ireland, 12
Spain
Vall d'Hebron University Hospital
Barcelona, Spain, 08035
Sweden
Uppsala University Hospital
Uppsala, Sweden, SE-75185
Switzerland
University Children's Hospital
Zurich, Switzerland, CH-8032
United Kingdom
Birmingham Children's Hospital
Birmingham, England, United Kingdom, B16 8ET
Institute of Child Health at University of Bristol
Bristol, England, United Kingdom, BS2 8AE
Addenbrooke's Hospital
Cambridge, England, United Kingdom, CB2 2QQ
Leeds Cancer Centre at St. James's University Hospital
Leeds, England, United Kingdom, LS9 7TF
Leicester Royal Infirmary
Leicester, England, United Kingdom, LE1 5WW
Royal Liverpool Children's Hospital, Alder Hey
Liverpool, England, United Kingdom, L12 2AP
Middlesex Hospital
London, England, United Kingdom, W1T 3AA
Great Ormond Street Hospital for Children
London, England, United Kingdom, WC1N 3JH
Royal Manchester Children's Hospital
Manchester, England, United Kingdom, M27 4HA
Sir James Spence Institute of Child Health at Royal Victoria Infirmary
Newcastle-Upon-Tyne, England, United Kingdom, NE1 4LP
Queen's Medical Centre
Nottingham, England, United Kingdom, NG7 2UH
Oxford Radcliffe Hospital
Oxford, England, United Kingdom, 0X3 9DU
Children's Hospital - Sheffield
Sheffield, England, United Kingdom, S10 2TH
Southampton General Hospital
Southampton, England, United Kingdom, SO16 6YD
Royal Marsden - Surrey
Sutton, England, United Kingdom, SM2 5PT
Royal Belfast Hospital for Sick Children
Belfast, Northern Ireland, United Kingdom, BT12 6BE
Royal Aberdeen Children's Hospital
Aberdeen, Scotland, United Kingdom, AB25 2ZG
Royal Hospital for Sick Children
Edinburgh, Scotland, United Kingdom, EH9 1LF
Royal Hospital for Sick Children
Glasgow, Scotland, United Kingdom, G3 8SJ
Childrens Hospital for Wales
Cardiff, Wales, United Kingdom, CF14 4XW
Sponsors and Collaborators
European Paediatric Soft Tissue Sarcoma Study Group
Italian Association for Pediatric Hematology Oncology
Cooperative Weichteilsarkom Studie
Children's Cancer and Leukaemia Group
Dutch Childhood Oncology Group
Investigators
Study Chair: Andrea Ferrari, MD Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Study Chair: Modesto Carli, MD Azienda Ospedaliera di Padova
Study Chair: Joern Treuner, MD Olgahospital
Study Chair: Bernadette Brennan, MD Royal Manchester Children's Hospital
Study Chair: Max Van Noesel, MD, PhD Erasmus MC - Sophia Children's Hospital
  More Information

ClinicalTrials.gov Identifier: NCT00334854     History of Changes
Other Study ID Numbers: CCLG-EPSSG-NRSTS-2005  CDR0000482277  EU-20620  EUDRACT-2005-001139-31  UKCCSG-CTA-21275/0215/001/0001  CCLG-EpSSG-STS-2006-03 
Study First Received: June 7, 2006
Last Updated: August 9, 2013

Keywords provided by National Cancer Institute (NCI):
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

Additional relevant MeSH terms:
Sarcoma
Histiocytoma
Histiocytoma, Benign Fibrous
Histiocytoma, Malignant Fibrous
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Fibrous Tissue
Neoplasms, Connective Tissue
Doxorubicin
Liposomal doxorubicin
Isophosphamide mustard
Ifosfamide
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on January 23, 2017