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

Ovarian Cancer Clinical Trial

Official title:

RANDOMISED TRIAL OF ADJUVANT CHEMOTHERAPY WITH HIGH-DOSE DOXORUBICIN, IFOSFAMIDE AND LENOGRASTIM IN HIGH GRADE SOFT TISSUE SARCOMA

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002641
• Other study ID #: EORTC-62931
• Secondary ID: EORTC-62931CAN-N
• Status: Completed
• Phase: Phase 3
• First received: November 1, 1999
• Last updated: August 7, 2014
• Start date: February 1995
• Est. completion date: June 2012

Study information

• Verified date: July 2002
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 350
• Est. completion date: June 2012
• Est. primary completion date: February 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years to 69 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically proven soft tissue sarcoma that is amenable to definitive surgery no more than 8 weeks after biopsy or inadequate surgery

• Eligible subtypes:

• 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

Study Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Endometrial Cancer
• Kidney Cancer
• Ovarian Cancer
• Pheochromocytoma
• Sarcoma

Intervention

Biological:
• filgrastim

Drug:
• doxorubicin hydrochloride

• ifosfamide

• isolated perfusion

Procedure:
• adjuvant therapy

• conventional surgery

Radiation:
• radiation therapy

Locations

Country	Name	City	State
Austria	Karl-Franzens-University Graz	Graz
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Belgium	Hopital Universitaire Erasme	Brussels
Belgium	Institut Jules Bordet	Brussels
Belgium	Universitair Ziekenhuis Antwerpen	Edegem
Belgium	U.Z. Gasthuisberg	Leuven
Canada	Tom Baker Cancer Center - Calgary	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Cancer Care Ontario-Hamilton Regional Cancer Centre	Hamilton	Ontario
Canada	Cancer Care Ontario-London Regional Cancer Centre	London	Ontario
Canada	Maisonneuve-Rosemont Hospital	Montreal	Quebec
Canada	McGill University	Montreal	Quebec
Canada	Ottawa Regional Cancer Centre	Ottawa	Ontario
Canada	Saint John Regional Hospital	Saint John	New Brunswick
Canada	Mount Sinai Hospital - Toronto	Toronto	Ontario
Canada	British Columbia Cancer Agency - Vancouver Island Cancer Centre	Victoria	British Columbia
Canada	CancerCare Manitoba	Winnipeg	Manitoba
Denmark	Aarhus Kommunehospital	Aarhus
Denmark	Rigshospitalet	Copenhagen
France	Centre Leon Berard	Lyon
France	CHU de la Timone	Marseille
France	Institut Gustave Roussy	Villejuif
Germany	Robert Roessle Klinik	Berlin
Germany	Universitaetsklinikum Essen	Essen
Germany	Universitaets-Krankenhaus Eppendorf	Hamburg
Germany	Klinikum Grosshadern	Munich
Germany	Eberhard Karls Universitaet	Tuebingen
Italy	Istituto Nazionale per lo Studio e la Cura dei Tumori	Milano (Milan)
Netherlands	Antoni van Leeuwenhoek Hospital	Amsterdam
Netherlands	Academisch Ziekenhuis Groningen	Groningen
Netherlands	Daniel Den Hoed Cancer Center at Erasmus University Medical Center	Rotterdam
Portugal	Instituto Portugues de Oncologia de Francisco Gentil - Centro de Lisboa	Lisbon
Slovakia	National Cancer Institute - Bratislava	Bratislava
Spain	Hospital de la Santa Cruz I Sant Pau	Barcelona
Switzerland	Inselspital, Bern	Bern
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne
Switzerland	Kantonsspital - St. Gallen	St. Gallen
United Kingdom	Royal Devon and Exeter Hospital	Exeter	England
United Kingdom	St. James's Hospital	Leeds	England
United Kingdom	Middlesex Hospital- Meyerstein Institute	London	England
United Kingdom	Royal Marsden NHS Trust - London	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

Sponsors (2)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC	Canadian Cancer Trials Group

Countries where clinical trial is conducted

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

References & Publications (1)

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.