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

Tracking Information
First Submitted Date ICMJE	November 1, 1999
First Posted Date ICMJE	January 27, 2003
Last Update Posted Date	September 17, 2013
Study Start Date ICMJE	July 1997
Primary Completion Date	Not Provided
Current Primary Outcome Measures ICMJE; (submitted: November 8, 2006)	Local progression-free survival
Original Primary Outcome Measures ICMJE	Not Provided
Change History	Complete list of historical versions of study NCT00003052 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: November 8, 2006)	Response as assessed by WHO criteria; Overall survival; Relapse-free survival; Acute and late complications as assessed by CTC v 1.0
Original Secondary Outcome Measures ICMJE	Not Provided
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Combination Chemotherapy With or Without Hyperthermia Therapy in Treating Patients With Soft Tissue Sarcoma
Official Title ICMJE	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
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.
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 Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Primary Purpose: Treatment
Condition ICMJE	Sarcoma
Intervention ICMJE	Drug: doxorubicin hydrochloride; Drug: etoposide; Drug: ifosfamide; Procedure: conventional surgery; Procedure: hyperthermia treatment; Radiation: radiation therapy
Study Arms	Not Provided
Publications *	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.; 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 Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group (EORTC-STBSG); European Society for Hyperthermic Oncology (ESHO). Neo-adjuvant chemotherapy alone or with regional hyperthermia for localised high-risk soft-tissue sarcoma: a randomised phase 3 multicentre study. Lancet Oncol. 2010 Jun;11(6):561-70. doi: 10.1016/S1470-2045(10)70071-1. Epub 2010 Apr 29.; 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.; Issels RD, Lindner LH, Verweij J, Wessalowski R, Reichardt P, Wust P, Ghadjar P, Hohenberger P, Angele M, Salat C, Vujaskovic Z, Daugaard S, Mella O, Mansmann U, Dürr HR, Knösel T, Abdel-Rahman S, Schmidt M, Hiddemann W, Jauch KW, Belka C, Gronchi A; European Organization for the Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group and the European Society for Hyperthermic Oncology. Effect of Neoadjuvant Chemotherapy Plus Regional Hyperthermia on Long-term Outcomes Among Patients With Localized High-Risk Soft Tissue Sarcoma: The EORTC 62961-ESHO 95 Randomized Clinical Trial. JAMA Oncol. 2018 Feb 15. doi: 10.1001/jamaoncol.2017.4996. [Epub ahead of print]; Knösel T, Altendorf-Hofmann A, Lindner L, Issels R, Hermeking H, Schuebbe G, Gibis S, Siemens H, Kampmann E, Kirchner T. Loss of p16(INK4a) is associated with reduced patient survival in soft tissue tumours, and indicates a senescence barrier. J Clin Pathol. 2014 Jul;67(7):592-8. doi: 10.1136/jclinpath-2013-202106. Epub 2014 Apr 19.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Estimated Enrollment ICMJE; (submitted: November 8, 2006)	340
Original Enrollment ICMJE	Not Provided
Actual Study Completion Date	June 2010
Primary Completion Date	Not Provided
Eligibility Criteria ICMJE	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
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years to 70 Years (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Germany
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00003052
Other Study ID Numbers ICMJE	CDR0000065699; EORTC-62961
Has Data Monitoring Committee	Not Provided
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Not Provided
Study Sponsor ICMJE	European Organisation for Research and Treatment of Cancer - EORTC
Collaborators ICMJE	The European Society for Hyperthermic Oncology
Investigators ICMJE	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
PRS Account	National Cancer Institute (NCI)
Verification Date	November 2006
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP