Clinical trial NCT00003212: Ifosfamide or Doxorubicin in Treating Patients With Advanced or Metastatic Soft Tissue Sarcoma
Official title: Randomized Phase III Trial of Two Investigational Schedules of Ifosfamide vs. Standard Dose Doxorubicin in Patients With Advanced or Metastatic Soft Tissue Sarcoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Sarcoma
Keywords: adult angiosarcoma
adult fibrosarcoma
adult leiomyosarcoma
adult liposarcoma
adult neurofibrosarcoma
adult synovial sarcoma
recurrent adult soft tissue sarcoma
adult malignant fibrous histiocytoma
adult malignant hemangiopericytoma
adult rhabdomyosarcoma
stage IV uterine sarcoma
recurrent uterine sarcoma
stage IV adult soft tissue sarcoma
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
First posted: 2004-03-12
Enrollment: 780
Sex: ALL
Minimum age (years): 15
Maximum age (years): 65
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 ifosfamide or doxorubicin is more effective for advanced or metastatic soft tissue sarcoma.

PURPOSE: Randomized phase III trial to compare the effectiveness of ifosfamide with that of doxorubicin in treating patients who have advanced or metastatic soft tissue sarcoma.

Detailed description: OBJECTIVES: I. Determine the progression free survival rate in patients with advanced or metastatic soft tissue sarcoma treated with either of two different regimens of ifosfamide or doxorubicin. II. Assess the toxic effects of these therapies and response rate in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are randomized into one of 3 arms (continuous ifosfamide, ifosfamide daily for 3 days, or doxorubicin). Patients are stratified by performance status (0 vs 1), liver involvement (no vs yes), histological type (leiomyosarcoma vs synovial sarcoma vs other), and histological grade (1 vs 2 vs 3). Arm I: Patients receive doxorubicin by bolus infusion for 5-20 minutes once every 3 weeks. Arm II: Patients receive ifosfamide by intravenous infusion for 4 hours on days 1, 2, and 3 every three weeks. Arm III: Patients receive ifosfamide by intravenous infusion for 72 hours every 3 weeks. Patients are assessed after every 2 courses of therapy. Each course of therapy consists of 3 weeks of treatment. Patients may receive a maximum of 6 courses of therapy in the absence of toxicity and disease progression. Patients are followed every 12 weeks for survival.

PROJECTED ACCRUAL: A total of 780 patients (260 per treatment arm) will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS: Histologically proven advanced or metastatic soft tissue sarcoma including the following: Malignant fibrous histiocytoma Liposarcoma Rhabdomyosarcoma Synovial sarcoma Malignant paraganglioma Fibrosarcoma Leiomyosarcoma Angiosarcoma including haemangiopericytoma Neurogenic sarcoma Unclassified sarcoma Mixed mesodermal tumor of the uterus Measurable disease with evidence of progression in prior 6 weeks No symptomatic or known CNS metastases

PATIENT CHARACTERISTICS: Age: 15 to 65 Performance status: WHO 0-1 Life expectancy: Not specified Hematopoietic: WBC at least 3000/mm3 Neutrophil count greater than 2,000/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater 1.75 mg/dL Albumin at least 25 g/L Renal: Creatinine clearance greater than 70 mL/min Cardiovascular: No history of uncontrolled cardiovascular disease Other: Fertile women must use effective contraception No other severe medical illness including psychosis No prior primary malignant tumor except: Adequately treated carcinoma in situ of the cervix Basal cell carcinoma

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior chemotherapy Endocrine therapy: Not specified Radiotherapy: No radiotherapy to the sole index lesion Surgery: Not specified

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Leuven
country: Belgium
facility: U.Z. Gasthuisberg
city: Aarhus
country: Denmark
facility: Aarhus Kommunehospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Lyon
country: France
facility: Centre Leon Berard
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Munich
country: Germany
facility: Klinikum Grosshadern
city: Budapest
country: Hungary
facility: National Institute of Oncology
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoekhuis
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Nijmegen
country: Netherlands
facility: University Medical Center Nijmegen
city: Rotterdam
country: Netherlands
facility: Rotterdam Cancer Institute
city: Warsaw
country: Poland
facility: Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology
city: Bratislava
country: Slovakia
facility: National Cancer Institute - Bratislava
city: Las Palmas
country: Spain
facility: Hospital Insular de Gran Canaria
city: Leeds
country: United Kingdom
facility: St. James's Hospital
state: England
city: London
country: United Kingdom
facility: Royal Marsden NHS Trust
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: The Christie NHS Foundation Trust
name: Paul C. Lorigan, MD
role: STUDY_CHAIR
References:
citation: Lorigan P, Verweij J, Papai Z, Rodenhuis S, Le Cesne A, Leahy MG, Radford JA, Van Glabbeke MM, Kirkpatrick A, Hogendoorn PC, Blay JY; European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study. Phase III trial of two investigational schedules of ifosfamide compared with standard-dose doxorubicin in advanced or metastatic soft tissue sarcoma: a European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study. J Clin Oncol. 2007 Jul 20;25(21):3144-50. doi: 10.1200/JCO.2006.09.7717.