Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Closed 18 to 70 Other EORTC-62961 NCT00003052

Objectives

1. 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.
2. Determine the tumor response rate, local disease control rate, and overall survival in patients treated with this regimen.

Entry Criteria

Disease Characteristics:

• 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

Prior/Concurrent Therapy:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

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

Surgery:

• See Disease Characteristics
• No prior mutilative surgery

Patient Characteristics:

Age:

• 18 to 70

Performance status:

• WHO 0-2

  OR

• Karnofsky 60-100%

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 3,500/mm³
• Platelet count at least 100,000/mm³
• No bleeding disorder

Hepatic:

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

Renal:

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

Cardiovascular:

• 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

Other:

• 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

Expected Enrollment

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

Outcomes

Local progression-free survival

Response as assessed by WHO criteria
Overall survival
Relapse-free survival
Acute and late complications as assessed by CTC v 1.0

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.

Issels RD, Lindner LH, Wust P, et al.: Regional hyperthermia (RHT) improves response and survival when combined with systemic chemotherapy in the management of locally advanced, high grade soft tissue sarcomas (STS) of the extremities, the body wall and the abdomen: a phase III randomised pros. [Abstract] J Clin Oncol 25 (Suppl 18): A-10009, 547s, 2007.

Lindner LH, Schlemmer M, Hohenberger P, et al.: Risk assessment of early progression among 213 pts with high-risk soft tissue sarcomas (HR-STS) treated with neoadjuvant chemotherapy regional hyperthermia: EORTC 62961/ESHO-RHT 95 intergroup phase III study. [Abstract] J Clin Oncol 23 (Suppl 16): A-9020, 821s, 2005.

Trial Contact Information

Trial Lead Organizations

European Organization for Research and Treatment of Cancer

Rolf Issels, MD, PhD, Study coordinator		Ph: 49-89-7095-4768 Email: Rolf.Issels@med.uni-muenchen.de

European Society For Hypothermic Oncology

Rolf Issels, MD, PhD, Protocol chair		Ph: 49-89-7095-4768 Email: Rolf.Issels@med.uni-muenchen.de

Registry Information
Official Title		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
Trial Start Date		1997-07-11
Registered in ClinicalTrials.gov		NCT00003052
Date Submitted to PDQ		1997-07-29
Information Last Verified		2006-11-19

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