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

Sarcoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003052
• Other study ID #: CDR0000065699
• Secondary ID: EORTC-62961
• Status: Completed
• Phase: Phase 3
• First received: November 1, 1999
• Last updated: September 16, 2013
• Start date: July 1997
• Est. completion date: June 2010

Study information

• Verified date: November 2006
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 340
• Est. completion date: June 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Sarcoma

Intervention

Drug:
• doxorubicin hydrochloride

• etoposide

• ifosfamide

Procedure:
• conventional surgery

• hyperthermia treatment

Radiation:
• radiation therapy

Locations

Country	Name	City	State
Germany	Robert Roessle Comprehensive Cancer Center at University of Berlin - Charite Campus Buch	Berlin
Germany	Universitaetsklinikum Essen	Essen
Germany	Universitaetsklinikum Hamburg-Eppendorf	Hamburg
Germany	Klinikum der Universitaet Muenchen - Grosshadern Campus	Munich

Sponsors (2)

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

Country where clinical trial is conducted

Germany, 

References & Publications (4)

Issels RD, Lindner LH, Verweij J, Wust P, Reichardt P, Schem BC, Abdel-Rahman S, Daugaard S, Salat C, Wendtner CM, Vujaskovic Z, Wessalowski R, Jauch KW, Dürr HR, Ploner F, Baur-Melnyk A, Mansmann U, Hiddemann W, Blay JY, Hohenberger P; European Organisat — View Citation

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 t

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

Stahl R, Wang T, Lindner LH, Abdel-Rahman S, Santl M, Reiser MF, Issels RD. Comparison of radiological and pathohistological response to neoadjuvant chemotherapy combined with regional hyperthermia (RHT) and study of response dependence on the applied thermal parameters in patients with soft tissue sarcomas (STS). Int J Hyperthermia. 2009 Jun;25(4):289-98. doi: 10.1080/02656730902873616. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Local progression-free survival			No
Secondary	Response as assessed by WHO criteria			No
Secondary	Overall survival			No
Secondary	Relapse-free survival			No
Secondary	Acute and late complications as assessed by CTC v 1.0			No