Clinical trial NCT00002641: Surgery With or Without Chemotherapy in Treating Patients With Soft Tissue Sarcoma
Official title: RANDOMISED TRIAL OF ADJUVANT CHEMOTHERAPY WITH HIGH-DOSE DOXORUBICIN, IFOSFAMIDE AND LENOGRASTIM IN HIGH GRADE SOFT TISSUE SARCOMA
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Endometrial Cancer
Kidney Cancer
Ovarian Cancer
Pheochromocytoma
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 alveolar soft-part sarcoma
adult epithelioid sarcoma
adult malignant fibrous histiocytoma
adult malignant hemangiopericytoma
adult malignant mesenchymoma
adult rhabdomyosarcoma
localized benign pheochromocytoma
regional pheochromocytoma
recurrent pheochromocytoma
stage II uterine sarcoma
stage III uterine sarcoma
recurrent uterine sarcoma
uterine carcinosarcoma
uterine leiomyosarcoma
endometrial stromal sarcoma
ovarian sarcoma
clear cell sarcoma of the kidney
stage II adult soft tissue sarcoma
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
Collaborators: name: NCIC Clinical Trials Group
First posted: 2003-01-27
Enrollment: 350
Sex: ALL
Minimum age (years): 16
Maximum age (years): 69
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Karl-Franzens-University Graz
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Brussels
country: Belgium
facility: Hopital Universitaire Erasme
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Leuven
country: Belgium
facility: U.Z. Gasthuisberg
city: Calgary
country: Canada
facility: Tom Baker Cancer Center - Calgary
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Victoria
country: Canada
facility: British Columbia Cancer Agency - Vancouver Island Cancer Centre
state: British Columbia
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Saint John
country: Canada
facility: Saint John Regional Hospital
state: New Brunswick
city: Hamilton
country: Canada
facility: Cancer Care Ontario-Hamilton Regional Cancer Centre
state: Ontario
city: London
country: Canada
facility: Cancer Care Ontario-London Regional Cancer Centre
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Regional Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital - Toronto
state: Ontario
city: Montreal
country: Canada
facility: Maisonneuve-Rosemont Hospital
state: Quebec
city: Montreal
country: Canada
facility: McGill University
state: Quebec
city: Aarhus
country: Denmark
facility: Aarhus Kommunehospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Lyon
country: France
facility: Centre Leon Berard
city: Marseille
country: France
facility: CHU de la Timone
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Berlin
country: Germany
facility: Robert Roessle Klinik
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
city: Hamburg
country: Germany
facility: Universitaets-Krankenhaus Eppendorf
city: Munich
country: Germany
facility: Klinikum Grosshadern
city: Tuebingen
country: Germany
facility: Eberhard Karls Universitaet
city: Milano (Milan)
country: Italy
facility: Istituto Nazionale per lo Studio e la Cura dei Tumori
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoek Hospital
city: Groningen
country: Netherlands
facility: Academisch Ziekenhuis Groningen
city: Rotterdam
country: Netherlands
facility: Daniel Den Hoed Cancer Center at Erasmus University Medical Center
city: Lisbon
country: Portugal
facility: Instituto Portugues de Oncologia de Francisco Gentil - Centro de Lisboa
city: Bratislava
country: Slovakia
facility: National Cancer Institute - Bratislava
city: Barcelona
country: Spain
facility: Hospital de la Santa Cruz I Sant Pau
city: Bern
country: Switzerland
facility: Inselspital, Bern
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: St. Gallen
country: Switzerland
facility: Kantonsspital - St. Gallen
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital
state: England
city: Leeds
country: United Kingdom
facility: St. James's Hospital
state: England
city: London
country: United Kingdom
facility: Royal Marsden NHS Trust - London
state: England
city: London
country: United Kingdom
facility: Middlesex Hospital- Meyerstein Institute
state: England
city: Manchester
country: United Kingdom
facility: Christie Hospital N.H.S. Trust
state: England
city: Newcastle Upon Tyne
country: United Kingdom
facility: Newcastle General Hospital
state: England
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital NHS Trust
state: England
city: Sheffield
country: United Kingdom
facility: Weston Park Hospital
state: England
Study officials:
affiliation: Cancer Research Centre at Weston Park Hospital
name: Penella J. Woll, MD, PhD
role: STUDY_CHAIR
affiliation: Tom Baker Cancer Centre - Calgary
name: Vivien H.C. Bramwell, MB, BS, PhD, FRCP
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.