Back to resultsCombination Chemotherapy With or Without Hyperthermia Therapy in Treating Patients With Soft Tissue Sarcoma
Primary Purpose
Sarcoma
Status
Completed
Phase
Phase 3
Locations
Germany
Study Type
Interventional
Intervention
doxorubicin hydrochloride
etoposide
ifosfamide
conventional surgery
hyperthermia treatment
radiation therapy
Sponsored by
About this trial
This is an interventional treatment trial for Sarcoma focused on measuring 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
Eligibility 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
Sites / Locations
- Robert Roessle Comprehensive Cancer Center at University of Berlin - Charite Campus Buch
- Universitaetsklinikum Essen
- Universitaetsklinikum Hamburg-Eppendorf
- Klinikum der Universitaet Muenchen - Grosshadern Campus
Outcomes
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
Full Information
NCT ID
NCT00003052
First Posted
November 1, 1999
Last Updated
September 16, 2013
Sponsor
European Organisation for Research and Treatment of Cancer - EORTC
Collaborators
The European Society for Hyperthermic Oncology
1. Study Identification
Unique Protocol Identification Number
NCT00003052
Brief Title
Combination Chemotherapy With or Without Hyperthermia Therapy in Treating Patients With Soft Tissue Sarcoma
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 Type
Interventional
2. Study Status
Record Verification Date
November 2006
Overall Recruitment Status
Completed
Study Start Date
July 1997 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
June 2010 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
European Organisation for Research and Treatment of Cancer - EORTC
Collaborators
The European Society for Hyperthermic Oncology
4. Oversight
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Allocation
Randomized
Enrollment
340 (Anticipated)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
doxorubicin hydrochloride
Intervention Type
Drug
Intervention Name(s)
etoposide
Intervention Type
Drug
Intervention Name(s)
ifosfamide
Intervention Type
Procedure
Intervention Name(s)
conventional surgery
Intervention Type
Procedure
Intervention Name(s)
hyperthermia treatment
Intervention Type
Radiation
Intervention Name(s)
radiation therapy
Primary Outcome Measure Information:
Title
Local progression-free survival
Secondary Outcome Measure Information:
Title
Response as assessed by WHO criteria
Title
Overall survival
Title
Relapse-free survival
Title
Acute and late complications as assessed by CTC v 1.0
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rolf D. Issels, MD, PhD
Organizational Affiliation
Klinikum der Universitaet Muenchen - Grosshadern Campus
First Name & Middle Initial & Last Name & Degree
Rolf D. Issels, MD, PhD
Organizational Affiliation
Klinikum der Universitaet Muenchen - Grosshadern Campus
Official's Role
Study Chair
Facility Information:
Facility Name
Robert Roessle Comprehensive Cancer Center at University of Berlin - Charite Campus Buch
City
Berlin
ZIP/Postal Code
D-13122
Country
Germany
Facility Name
Universitaetsklinikum Essen
City
Essen
ZIP/Postal Code
D-45122
Country
Germany
Facility Name
Universitaetsklinikum Hamburg-Eppendorf
City
Hamburg
ZIP/Postal Code
D-20246
Country
Germany
Facility Name
Klinikum der Universitaet Muenchen - Grosshadern Campus
City
Munich
ZIP/Postal Code
D-81377
Country
Germany
12. IPD Sharing Statement
Citations:
PubMed Identifier
19670096
Citation
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.
Results Reference
background
PubMed Identifier
20434400
Citation
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.
Results Reference
result
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 the abdomen: a phase III randomised pros. [Abstract] J Clin Oncol 25 (Suppl 18): A-10009, 547s, 2007.
Results Reference
result
Citation
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.
Results Reference
result
PubMed Identifier
34666214
Citation
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 Oct 16;158:123-132. doi: 10.1016/j.ejca.2021.09.015. Online ahead of print.
Results Reference
derived
PubMed Identifier
29450452
Citation
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. Erratum In: JAMA Oncol. 2018 Apr 1;4(4):590.
Results Reference
derived
PubMed Identifier
24747207
Citation
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.
Results Reference
derived
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Combination Chemotherapy With or Without Hyperthermia Therapy in Treating Patients With Soft Tissue Sarcoma
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