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AzTrials

SarcomaPhase 3NCT00003052

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

A Phase 3 study testing doxorubicin hydrochloride, etoposide and ifosfamide in people with Sarcoma, run by European Organisation for Research and Treatment of Cancer - EORTC at 4 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Sarcoma
What is being tested?
doxorubicin hydrochloride, etoposide and ifosfamide
Type of treatment
Surgery or procedure
How many people
340 participants
Where
4 sitesGermany
Study dates
Jul 1997to Jun 2010
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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

Trial locations and contacts

4 sites in 1 country.

Germany4 sites

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

    Berlin, D-13122

  • Universitaetsklinikum Essen

    Essen, D-45122

  • Universitaetsklinikum Hamburg-Eppendorf

    Hamburg, D-20246

  • Klinikum der Universitaet Muenchen - Grosshadern Campus

    Munich, D-81377

Other trials in Germany

About this study

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

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.

Read the 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.

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
Medical subject headings
Sarcoma, Hemangiosarcoma, Fibrosarcoma, Leiomyosarcoma, Liposarcoma, Neurofibrosarcoma, Sarcoma, Synovial, Histiocytoma, Malignant Fibrous

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Local progression-free survival

Secondary outcomes (4)

  1. Response as assessed by WHO criteria

  2. Overall survival

  3. Relapse-free survival

  4. Acute and late complications as assessed by CTC v 1.0

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jan 2003 (estimated)
  2. Study startJul 1997
  3. Study completionJun 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Enrolment
340 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00003052
Sponsor's protocol ID
CDR0000065699
Other IDs
EORTC-62961
Status last verified
Nov 2006
First submitted
1 Nov 1999
Last updated
17 Sep 2013
Results posted
No

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.

    PubMed 19670096

  • 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.

    PubMed 20434400

  • 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.

  • Albertsmeier M, Milani V, Lindner LH, Tine G, Pasquali S, Callegaro D, Gronchi A, Durr HR, Klein A, Di Gioia D, Abdel-Rahman S, Schmidt M, Werner J, von Bergwelt-Baildon M, Miceli R, Issels R. Neoadjuvant chemotherapy for soft-tissue sarcoma of the extremities: A post-hoc Sarculator-based risk analysis of the EORTC 62961-ESHO 95 randomized trial. Cancer. 2026 May 1;132(9):e70427. doi: 10.1002/cncr.70427.

    PubMed 42035475

  • 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.

    PubMed 34666214

  • 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.

    PubMed 29450452

  • 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.

    PubMed 24747207

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing doxorubicin hydrochloride, etoposide and ifosfamide in people with Sarcoma, run by European Organisation for Research and Treatment of Cancer - EORTC at 4 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Sep 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Local progression-free survival. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00003052, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2013.

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