Combination Chemotherapy With or Without Hyperthermia Therapy in Treating Patients With Soft Tissue Sarcoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00003052
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : September 17, 2013
The European Society for Hyperthermic Oncology
Information provided by:
National Cancer Institute (NCI)

November 1, 1999
January 27, 2003
September 17, 2013
July 1997
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Local progression-free survival
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Complete list of historical versions of study NCT00003052 on Archive Site
  • Response as assessed by WHO criteria
  • Overall survival
  • Relapse-free survival
  • Acute and late complications as assessed by CTC v 1.0
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Combination Chemotherapy With or Without Hyperthermia Therapy in Treating Patients With Soft Tissue Sarcoma
Randomized Study Comparing Neoadjuvant Chemotherapy Etoposide + Ifosfamide + Adriamycin (EIA) Combined With Regional Hyperthermia (RHT) Versus Neoadjuvant Chemotherapy Alone in the Treatment of High-Risk Soft Tissue Sarcomas in Adults

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Hyperthermia therapy kills tumor cells by heating them to several degrees above body temperature. It is not known whether receiving chemotherapy plus hyperthermia is more effective than receiving chemotherapy alone in treating patients with soft tissue sarcoma.

PURPOSE: This randomized phase III trial is studying combination chemotherapy alone to see how well it works compared to combination chemotherapy and hyperthermia therapy in treating patients with soft tissue sarcoma.


  • Determine local progression-free survival of patients with high-risk soft tissue sarcoma treated with neoadjuvant etoposide, ifosfamide, and doxorubicin with or without regional hyperthermia.
  • Determine the tumor response rate, local disease control rate, and overall survival in patients treated with this regimen.

OUTLINE: This is a randomized study. Patients are stratified according to high-risk category (S1 vs S2 vs S3) and disease site (extremity vs nonextremity). Patients are randomized to one of two treatment arms.

  • Arm I: Patients receive etoposide IV over 30 minutes on days 1 and 4, ifosfamide IV over 60 minutes on days 1-4, and doxorubicin IV over 30 minutes on day 1. Treatment continues every 21 days for a total of 4 courses. Patients also undergo regional hyperthermia.
  • Arm II: Patients receive chemotherapy alone as in arm I. Patients in both arms undergo definitive surgery 4-6 weeks after chemotherapy. Patients also undergo radiotherapy beginning 4-6 weeks after surgery. After completion of surgery and radiotherapy, patients with non-resectable tumors showing no disease progression receive an additional 4 courses of chemotherapy with or without regional hyperthermia according to above treatment schedule.

Patients are followed every 3 months for 1 year, every 4 months for 2 years, and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 340 patients (170 patients per arm) will be accrued for this study within 3.5 years.

Phase 3
Allocation: Randomized
Primary Purpose: Treatment
  • Drug: doxorubicin hydrochloride
  • Drug: etoposide
  • Drug: ifosfamide
  • Procedure: conventional surgery
  • Procedure: hyperthermia treatment
  • Radiation: radiation therapy
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*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
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June 2010
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  • Histologically proven grade II or III soft tissue sarcoma of one of following high-risk groups:

    • Grade II/III primary tumor with lesion size of at least 5 cm, deep, and extracompartmental (S1)
    • Local recurrence of primary tumor (S2)
    • Inadequate surgical excision of S1 or S2 (S3)
  • Disease recurrence after prior surgery allowed
  • The following histological types are eligible:

    • Malignant fibrous histiocytoma
    • Liposarcoma (round cell and pleomorphic)
    • Leiomyosarcoma
    • Fibrosarcoma
    • Rhabdomyosarcoma
    • Synovial sarcoma
    • Malignant paraganglioma
    • Neurofibrosarcoma (malignant schwannoma)
    • Extraskeletal Ewing's sarcoma
    • Extraskeletal osteosarcoma
    • Malignant peripheral neuroectodermal tumors
    • Mesenchymal chondrosarcoma
    • Angiosarcoma
    • Miscellaneous sarcoma
    • Unclassified sarcoma
  • No distant metastases



  • 18 to 70

Performance status:

  • WHO 0-2 OR
  • Karnofsky 60-100%

Life expectancy:

  • Not specified


  • WBC at least 3,500/mm^3
  • Platelet count at least 100,000/mm^3
  • No bleeding disorder


  • Bilirubin less than 1.25 times upper limit of normal
  • No severe hepatic dysfunction


  • Creatinine clearance greater than 60 mL/min
  • No chronic renal failure


  • No documented existing cardiac failure
  • No manifest heart failure (New York Heart Association class III or IV)
  • Left ventricular ejection fraction no more than 10% below institutional normal


  • No other prior or concurrent malignancy except adequately treated basal cell skin cancer or carcinoma in situ of the cervix
  • No other severe disease
  • No severe cerebrovascular disease
  • No extremely obese patients
  • No prior metallic implants relevant to the regional hyperthermia field
  • Not pregnant or nursing


Biologic therapy:

  • Not specified


  • No prior chemotherapy

Endocrine therapy:

  • Not specified


  • No prior radiotherapy (except to disease recurrence outside study irradiation field)


  • See Disease Characteristics
  • No prior mutilative surgery
Sexes Eligible for Study: All
18 Years to 70 Years   (Adult, Older Adult)
Contact information is only displayed when the study is recruiting subjects
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European Organisation for Research and Treatment of Cancer - EORTC
The European Society for Hyperthermic Oncology
Investigator: Rolf D. Issels, MD, PhD Klinikum der Universitaet Muenchen - Grosshadern Campus
Study Chair: Rolf D. Issels, MD, PhD Klinikum der Universitaet Muenchen - Grosshadern Campus
National Cancer Institute (NCI)
November 2006

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP