Combination Chemotherapy With or Without Hyperthermia Therapy in Treating Patients With Soft Tissue Sarcoma - Full Text View

Purpose

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	Intervention	Phase
Sarcoma	Drug: doxorubicin hydrochloride Drug: etoposide Drug: ifosfamide Procedure: conventional surgery Procedure: hyperthermia treatment Radiation: radiation therapy	Phase 3


Study Type:	Interventional
Study Design:	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

Resource links provided by NLM:

MedlinePlus related topics: Fever Soft Tissue Sarcoma

Drug Information available for: Ifosfamide Doxorubicin Doxorubicin hydrochloride Etoposide

Genetic and Rare Diseases Information Center resources: Bone Cancer Dermatofibroma Fibrosarcoma Leiomyosarcoma Liposarcoma Malignant Fibrous Histiocytoma Malignant Mesenchymal Tumor Malignant Peripheral Nerve Sheath Tumor Neurofibrosarcoma Osteosarcoma Soft Tissue Sarcoma Synovial Sarcoma

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Local progression-free survival [ Designated as safety issue: No ]

Secondary Outcome Measures:

Response as assessed by WHO criteria [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]
Relapse-free survival [ Designated as safety issue: No ]
Acute and late complications as assessed by CTC v 1.0 [ Designated as safety issue: No ]


Estimated Enrollment:	340
Study Start Date:	July 1997
Study Completion Date:	June 2010

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.

Eligibility


Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003052

Locations


Germany
Robert Roessle Comprehensive Cancer Center at University of Berlin - Charite Campus Buch
Berlin, Germany, D-13122
Universitaetsklinikum Essen
Essen, Germany, D-45122
Universitaetsklinikum Hamburg-Eppendorf
Hamburg, Germany, D-20246
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


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

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

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.

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.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.


ClinicalTrials.gov Identifier:	NCT00003052 History of Changes
Other Study ID Numbers:	CDR0000065699, EORTC-62961
Study First Received:	November 1, 1999
Last Updated:	September 16, 2013
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):


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

Additional relevant MeSH terms:


Sarcoma Neoplasms Neoplasms by Histologic Type Neoplasms, Connective and Soft Tissue Doxorubicin Liposomal doxorubicin Antibiotics, Antineoplastic	Antineoplastic Agents Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Therapeutic Uses Topoisomerase II Inhibitors Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on February 27, 2015