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

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC (Other)

Overall Status

Completed

CT.gov ID

NCT00003052

Collaborator

The European Society for Hyperthermic Oncology (Other)

340

Enrollment

Locations

155

Duration (Months)

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Sarcoma	Drug: doxorubicin hydrochloride Drug: etoposide Drug: ifosfamide Procedure: conventional surgery Procedure: hyperthermia treatment Radiation: radiation therapy	Phase 3

Detailed Description

OBJECTIVES:

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

340 participants

Allocation:

Randomized

Primary Purpose:

Treatment

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

Study Start Date :

Jul 1, 1997

Actual Study Completion Date :

Jun 1, 2010

Outcome Measures

Primary Outcome Measures

Local progression-free survival []

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

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/mm^3
Platelet count at least 100,000/mm^3
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

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Robert Roessle Comprehensive Cancer Center at University of Berlin - Charite Campus Buch	Berlin	Germany	D-13122
2	Universitaetsklinikum Essen	Essen	Germany	D-45122
3	Universitaetsklinikum Hamburg-Eppendorf	Hamburg	Germany	D-20246
4	Klinikum der Universitaet Muenchen - Grosshadern Campus	Munich	Germany	D-81377

Sponsors and Collaborators

European Organisation for Research and Treatment of Cancer - EORTC
The European Society for Hyperthermic Oncology

Investigators

: Rolf D. Issels, MD, PhD, Klinikum der Universitaet Muenchen - Grosshadern Campus
Study Chair: Rolf D. Issels, MD, PhD, Klinikum der Universitaet Muenchen - Grosshadern Campus