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

NCT00003052 | Completed Phase 3

• 2 other identifiers: CDR0000065699EORTC-62961
• Study Type: interventional
• Target: 340
• Locations: 1 country
• Sites: 4

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.

Conditions

Sarcoma

Keywords

adult angiosarcoma; adult fibrosarcoma; adult leiomyosarcoma; adult liposarcoma; adult neurofibrosarcoma; adult synovial sarcoma; stage III adult soft tissue sarcoma; recurrent adult soft tissue sarcoma; adult extraskeletal osteosarcoma; adult malignant fibrous histiocytoma; adult rhabdomyosarcoma; stage I adult soft tissue sarcoma; stage II adult soft tissue sarcoma

Outcome Measures

Primary Outcomes (1)

• Local progression-free survival

Secondary Outcomes (4)

• Response as assessed by WHO criteria

• Overall survival

• Relapse-free survival

• Acute and late complications as assessed by CTC v 1.0

Interventions

doxorubicin hydrochloride DRUG

etoposide DRUG

ifosfamide DRUG

conventional surgery PROCEDURE

hyperthermia treatment PROCEDURE

radiation therapy RADIATION

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead
• The European Society for Hyperthermic Oncology: collaborator

Study Sites (4)

Robert Roessle Comprehensive Cancer Center at University of Berlin - Charite Campus Buch

Berlin, D-13122, Germany

Location

Universitaetsklinikum Essen

Essen, D-45122, Germany

Location

Universitaetsklinikum Hamburg-Eppendorf

Hamburg, D-20246, Germany

Location

Klinikum der Universitaet Muenchen - Grosshadern Campus

Munich, D-81377, Germany

Location

Related Publications (7)

• 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.

  PMID: 19670096 BACKGROUND

• 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, Durr 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.

  PMID: 20434400 RESULT

• 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.

  RESULT

• 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.

  RESULT

• Issels RD, Noessner E, Lindner LH, Schmidt M, Albertsmeier M, Blay JY, Stutz E, Xu Y, Buecklein V, Altendorf-Hofmann A, Abdel-Rahman S, Mansmann U, von Bergwelt-Baildon M, Knoesel T. Immune infiltrates in patients with localised high-risk soft tissue sarcoma treated with neoadjuvant chemotherapy without or with regional hyperthermia: A translational research program of the EORTC 62961-ESHO 95 randomised clinical trial. Eur J Cancer. 2021 Nov;158:123-132. doi: 10.1016/j.ejca.2021.09.015. Epub 2021 Oct 16.

  PMID: 34666214 DERIVED

• 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, Durr HR, Knosel 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 Apr 1;4(4):483-492. doi: 10.1001/jamaoncol.2017.4996.

  PMID: 29450452 DERIVED

• Knosel 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.

  PMID: 24747207 DERIVED

MeSH Terms

Conditions

Sarcoma; Hemangiosarcoma; Fibrosarcoma; Leiomyosarcoma; Liposarcoma; Neurofibrosarcoma; Sarcoma, Synovial; Histiocytoma, Malignant Fibrous; Rhabdomyosarcoma

Interventions

Doxorubicin; Etoposide; Ifosfamide; Diathermy; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Vascular Tissue; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Neoplasms, Muscle Tissue; Neoplasms, Adipose Tissue; Neurofibroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Peripheral Nervous System Neoplasms; Nervous System Neoplasms; Nervous System Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases; Histiocytoma; Myosarcoma

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hyperthermia, Induced; Therapeutics

Study Officials

• Rolf D. Issels, MD, PhD

  Klinikum der Universitaet Muenchen - Grosshadern Campus

• Rolf D. Issels, MD, PhD

  Klinikum der Universitaet Muenchen - Grosshadern Campus

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Purpose: TREATMENT
• Sponsor Type: NETWORK

Study Record Dates

• First Submitted: November 1, 1999
• First Posted: January 27, 2003
• Study Start: July 1, 1997
• Study Completion: June 1, 2010
• Last Updated: September 17, 2013

Record last verified: 2006-11

Locations

DE (4)