Surgery With or Without Chemotherapy in Treating Patients With Soft Tissue Sarcoma

NCT ID: NCT00002641

Last Updated: 2014-08-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 350 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1995-02-28
• Study Completion Date: 2012-06-30

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether giving chemotherapy after surgery is more effective than surgery alone in treating soft tissue sarcoma.

PURPOSE: Randomized phase III trial to compare the effectiveness of surgery with or without chemotherapy in treating patients who have soft tissue sarcoma.

Detailed Description

OBJECTIVES:

• Compare the local disease control, overall survival, and relapse-free survival in patients with high-grade soft tissue sarcoma treated with adjuvant high-dose doxorubicin and ifosfamide plus filgrastim (G-CSF) vs no adjuvant chemotherapy and G-CSF after definitive surgery.
• Compare the toxicity and morbidity of these regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to center, site of primary tumor (extremity vs trunk, including shoulder, pelvic girdle, head, or neck vs central, including intrathoracic, visceral, uterine, or retroperitoneal), size of primary tumor (less than 5 cm vs 5 cm or greater in largest diameter), postoperative radiotherapy (yes vs no), and isolated limb perfusion therapy (yes vs no).

Some patients undergo isolated limb perfusion therapy with cytotoxics and/or cytokines.

No more than 8 weeks after biopsy or inadequate surgery, patients undergo definitive surgery. Patients with complete resection undergo radiotherapy assessment and then randomization. Patients with incomplete or marginal resection (except for central lesions) undergo re-excision and, in the absence of macroscopic disease, assessment for postoperative radiotherapy followed by randomization.

• Randomization: Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive no adjuvant chemotherapy or filgrastim (G-CSF). Beginning within 6 weeks after surgery, eligible patients undergo radiotherapy as outlined below.
• Arm II: Beginning within 4 weeks after surgery, patients receive high-dose doxorubicin IV over 20 minutes followed by ifosfamide IV over 24 hours and G-CSF subcutaneously daily beginning 24 hours after completion of ifosfamide infusion and continuing for 10 days. Treatment continues every 3 weeks for 5 courses. Beginning within 6 weeks after completion of chemotherapy, eligible patients undergo radiotherapy as outlined below.
• Radiotherapy: Patients with incomplete or marginal resection undergo radiotherapy 5 days a week for 6-6.6 weeks. Patients with complete microscopic resection undergo radiotherapy 5 days a week for 5 weeks followed by boost radiotherapy 5 days a week for 1 week.

Patients are followed every 2 months for 1 year, every 3 months for 2 years, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 350 patients will be accrued for this study within 3.5 years.

Conditions

Endometrial Cancer; Kidney Cancer; Ovarian Cancer; Pheochromocytoma; Sarcoma

Study Design

• Allocation Method: RANDOMIZED
• Primary Study Purpose: TREATMENT

Interventions

filgrastim

Intervention Type: BIOLOGICAL

doxorubicin hydrochloride

Intervention Type: DRUG

ifosfamide

Intervention Type: DRUG

isolated perfusion

Intervention Type: DRUG

adjuvant therapy

Intervention Type: PROCEDURE

conventional surgery

Intervention Type: PROCEDURE

radiation therapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• Alveolar soft part sarcoma
• Angiosarcoma
• Fibrosarcoma
• Leiomyosarcoma
• Malignant fibrous histiocytoma
• Liposarcoma (round cell and pleomorphic)
• Miscellaneous sarcoma (including pelvic mixed mesodermal tumors)
• Malignant paraganglioma
• Neurogenic sarcoma
• Rhabdomyosarcoma
• Synovial sarcoma
• Unclassifiable sarcoma
• Ineligible subtypes:

• Chondrosarcoma
• Dermatofibrosarcoma
• Embryonal rhabdomyosarcoma
• Ewing's sarcoma
• Kaposi's sarcoma
• Liposarcoma (myxoid and well differentiated)
• Malignant mesothelioma
• Neuroblastoma
• Osteosarcoma
• Confirmed high-grade tumor (i.e., Trojani Grade II or III)
• No metastases on staging with chest x-ray and thoracic CT scan
• No regional lymph node involvement
• Locally recurrent disease allowed

• Interval of 3 months or more between definitive surgery and recurrence

PATIENT CHARACTERISTICS:

Age:

• 16 to 69

Performance status:

• WHO 0-1

Life expectancy:

• Not specified

Hematopoietic:

• WBC greater than 4,000/mm^3
• Platelet count greater than 120,000/mm^3
• No bleeding disorders

Hepatic:

• Bilirubin no greater than 1.25 times normal
• No severe hepatic dysfunction

Renal:

• Creatinine less than 1.6 mg/dL OR
• Creatinine clearance greater than 60 mL/min

Cardiovascular:

• No clear history of angina
• No documented myocardial infarction
• No existing cardiac failure

Other:

• No serious infection
• No other malignancy except adequately treated carcinoma in situ of the cervix or basal cell or squamous cell skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior systemic chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy to affected area

Surgery:

• See Disease Characteristics

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 69 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

NCIC Clinical Trials Group

NETWORK

Sponsor Role: collaborator

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Penella J. Woll, MD, PhD

Role: STUDY_CHAIR

Cancer Research Centre at Weston Park Hospital

Vivien H.C. Bramwell, MB, BS, PhD, FRCP

Role: STUDY_CHAIR

Tom Baker Cancer Centre - Calgary

Locations

Karl-Franzens-University Graz

Graz, , Austria

Institut Jules Bordet

Brussels, , Belgium

Hopital Universitaire Erasme

Brussels, , Belgium

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

Universitair Ziekenhuis Antwerpen

Edegem, , Belgium

U.Z. Gasthuisberg

Leuven, , Belgium

Tom Baker Cancer Center - Calgary

Calgary, Alberta, Canada

Cross Cancer Institute

Edmonton, Alberta, Canada

British Columbia Cancer Agency - Vancouver Island Cancer Centre

Victoria, British Columbia, Canada

CancerCare Manitoba

Winnipeg, Manitoba, Canada

Saint John Regional Hospital

Saint John, New Brunswick, Canada

Cancer Care Ontario-Hamilton Regional Cancer Centre

Hamilton, Ontario, Canada

Cancer Care Ontario-London Regional Cancer Centre

London, Ontario, Canada

Ottawa Regional Cancer Centre

Ottawa, Ontario, Canada

Mount Sinai Hospital - Toronto

Toronto, Ontario, Canada

Maisonneuve-Rosemont Hospital

Montreal, Quebec, Canada

McGill University

Montreal, Quebec, Canada

Aarhus Kommunehospital

Aarhus, , Denmark

Rigshospitalet

Copenhagen, , Denmark

Centre Leon Berard

Lyon, , France

CHU de la Timone

Marseille, , France

Institut Gustave Roussy

Villejuif, , France

Robert Roessle Klinik

Berlin, , Germany

Universitaetsklinikum Essen

Essen, , Germany

Universitaets-Krankenhaus Eppendorf

Hamburg, , Germany

Klinikum Grosshadern

Munich, , Germany

Eberhard Karls Universitaet

Tübingen, , Germany

Istituto Nazionale per lo Studio e la Cura dei Tumori

Milano (Milan), , Italy

Antoni van Leeuwenhoek Hospital

Amsterdam, , Netherlands

Academisch Ziekenhuis Groningen

Groningen, , Netherlands

Daniel Den Hoed Cancer Center at Erasmus University Medical Center

Rotterdam, , Netherlands

Instituto Portugues de Oncologia de Francisco Gentil - Centro de Lisboa

Lisbon, , Portugal

National Cancer Institute - Bratislava

Bratislava, , Slovakia

Hospital de la Santa Cruz I Sant Pau

Barcelona, , Spain

Inselspital, Bern

Bern, , Switzerland

Centre Hospitalier Universitaire Vaudois

Lausanne, , Switzerland

Kantonsspital - St. Gallen

Sankt Gallen, , Switzerland

Royal Devon and Exeter Hospital

Exeter, England, United Kingdom

St. James's Hospital

Leeds, England, United Kingdom

Royal Marsden NHS Trust - London

London, England, United Kingdom

Middlesex Hospital- Meyerstein Institute

London, England, United Kingdom

Christie Hospital N.H.S. Trust

Manchester, England, United Kingdom

Newcastle General Hospital

Newcastle upon Tyne, England, United Kingdom

Nottingham City Hospital NHS Trust

Nottingham, England, United Kingdom

Weston Park Hospital

Sheffield, England, United Kingdom

Countries

Austria; Belgium; Canada; Denmark; France; Germany; Italy; Netherlands; Portugal; Slovakia; Spain; Switzerland; United Kingdom

References

Le Cesne A, Van Glabbeke M, Woll PJ, et al.: The end of adjuvant chemotherapy (adCT) era with doxorubicin-based regimen in resected high-grade soft tissue sarcoma (STS): pooled analysis of the two STBSG-EORTC phase III clinical trials. [Abstract] J Clin Oncol 26 (Suppl 15): A-10525, 2008.

Reference Type: BACKGROUND

Woll PJ, Reichardt P, Le Cesne A, Bonvalot S, Azzarelli A, Hoekstra HJ, Leahy M, Van Coevorden F, Verweij J, Hogendoorn PC, Ouali M, Marreaud S, Bramwell VH, Hohenberger P; EORTC Soft Tissue and Bone Sarcoma Group and the NCIC Clinical Trials Group Sarcoma Disease Site Committee. Adjuvant chemotherapy with doxorubicin, ifosfamide, and lenograstim for resected soft-tissue sarcoma (EORTC 62931): a multicentre randomised controlled trial. Lancet Oncol. 2012 Oct;13(10):1045-54. doi: 10.1016/S1470-2045(12)70346-7. Epub 2012 Sep 4.

Reference Type: DERIVED

PMID: 22954508 (View on PubMed)

Other Identifiers

EORTC-62931

Identifier Type: -

Identifier Source: secondary_id

CAN-NCIC-SR3

Identifier Type: -

Identifier Source: secondary_id

EORTC-62931

Identifier Type: -

Identifier Source: org_study_id