Clinical trial NCT00061984: Doxorubicin With or Without Ifosfamide and Pegfilgrastim in Treating Patients With Locally Advanced or Metastatic Soft Tissue Sarcoma
Official title: Randomised Trial Of Single Agent Doxorubicin Versus Doxorubicin Plus Ifosfamide In The First Line Treatment Of Advanced Or Metastatic Soft Tissue Sarcoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Sarcoma
Keywords: adult angiosarcoma
adult epithelioid sarcoma
adult fibrosarcoma
adult leiomyosarcoma
adult liposarcoma
adult rhabdomyosarcoma
adult synovial sarcoma
stage III adult soft tissue sarcoma
adult malignant fibrous histiocytoma
adult neurofibrosarcoma
stage II adult soft tissue sarcoma
stage IV adult soft tissue sarcoma
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
First posted: 2003-06-06
Enrollment: 455
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy such as doxorubicin and ifosfamide use different ways to stop tumor cells from dividing so they stop growing or die. Colony-stimulating factors, such as pegfilgrastim, cause the body to make blood cells. It is not yet known whether doxorubicin alone is more effective with or without ifosfamide and pegfilgrastim in treating soft tissue sarcoma.

PURPOSE: This randomized phase III trial is studying giving doxorubicin alone to see how well it works compared to giving doxorubicin together with ifosfamide and pegfilgrastim in treating patients with locally advanced or metastatic soft tissue sarcoma.

Detailed description: OBJECTIVES:

* Compare the progression-free and overall survival of patients with locally advanced or metastatic soft tissue sarcoma treated with doxorubicin with vs without ifosfamide and pegfilgrastim as first-line therapy.
* Compare the response in patients treated with these regimens.
* Compare the treatment-related mortality of patients treated with these regimens.
* Compare the toxicity of these regimens in these patients.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to WHO performance status (0 vs 1), age group (less than 50 years of age vs 50 years of age and over), presence of liver metastases (yes vs no), histological grade (2 vs 3), and participating center. Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive doxorubicin IV on day 1 (or IV continuously on days 1-3).
* Arm II: Patients receive doxorubicin IV on days 1-3 and ifosfamide IV over 4 hours on days 1-4. Patients also receive pegfilgrastim subcutaneously on day 5.

In both arms, treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 8 weeks until disease progression and then every 12 weeks thereafter.

PROJECTED ACCRUAL: A total of 450 patients will be accrued for this study within 4 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed soft tissue sarcoma

  * Locally advanced unresectable\* OR metastatic disease
  * High-grade (grade 2-3) disease according to the FNLCC grading system NOTE: \*Disease that could prove resectable (including pulmonary metastasectomy) after a response to chemotherapy is allowed
* The following tumor types are eligible:

  * Malignant fibrous histiocytoma
  * Myxoid and round cell liposarcoma, pleomorphic liposarcoma, or dedifferentiated liposarcoma
  * Pleomorphic rhabdomyosarcoma
  * Synovial sarcoma
  * Myxofibrosarcoma, intermediate and high-grade
  * Fibrosarcoma
  * Leiomyosarcoma
  * Angiosarcoma
  * Malignant peripheral nerve sheath tumor
  * Epithelioid sarcoma
  * Alveolar rhabdomyosarcoma
  * Unclassifiable sarcoma, not otherwise specified
* The following tumor types are not eligible:

  * Gastrointestinal stromal tumor
  * Mixed mesodermal tumor
  * Chondrosarcoma
  * Malignant mesothelioma
  * Neuroblastoma
  * Osteosarcoma
  * Ewing's sarcoma/primitive neuroectodermal tumor
  * Desmoplastic small round cell tumor
  * Embryonal rhabdomyosarcoma
  * Alveolar soft part sarcoma
* Must have a measurable lesion with clinical evidence of progression within the past 6 weeks

  * Osseous lesions and pleural effusions are not considered measurable
* No known or symptomatic CNS metastases

PATIENT CHARACTERISTICS:

Age

* 18 to 60

Performance status

* WHO 0-1

Life expectancy

* Not specified

Hematopoietic

* Absolute neutrophil count at least 2,000/mm\^3
* Platelet count at least 100,000/mm\^3

Hepatic

* Bilirubin no greater than 1.8 mg/dL
* Albumin at least 2.5 g/dL

Renal

* Creatinine no greater than 1.4 mg/dL OR
* Creatinine clearance greater than 65 mL/min

Cardiovascular

* No history of cardiovascular disease

Other

* Not pregnant
* Negative pregnancy test
* Fertile patients must use effective contraception
* No other severe medical illness
* No psychosis
* No other prior or concurrent malignancy except adequately treated carcinoma in situ of the cervix or basal cell skin cancer
* No psychological, familial, sociological, or geographical condition that would preclude study compliance and follow-up schedule

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Not specified

Chemotherapy

* No prior chemotherapy for advanced or metastatic disease
* Prior adjuvant chemotherapy allowed provided there was no disease progression within 6 months after completion of treatment

Endocrine therapy

* Not specified

Radiotherapy

* No prior radiotherapy to the sole index lesion

Surgery

* Not specified

Primary outcomes:
measure: Overall survival
Secondary outcomes:
measure: Response as assessed by RECIST criteria
measure: Toxicity as assessed by CTC 2.0
measure: Treatment-related mortality
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Karl-Franzens-University Graz
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Leuven
country: Belgium
facility: U.Z. Gasthuisberg
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre - Calgary
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute at University of Alberta
state: Alberta
city: St. John's
country: Canada
facility: Doctor H. Bliss Murphy Cancer Centre
state: Newfoundland and Labrador
city: Hamilton
country: Canada
facility: Margaret and Charles Juravinski Cancer Centre
state: Ontario
city: Montreal
country: Canada
facility: McGill Cancer Centre at McGill University
state: Quebec
city: Aarhus
country: Denmark
facility: Aarhus Universitetshospital - Aarhus Sygehus
city: Copenhagen
country: Denmark
facility: Copenhagen County Herlev University Hospital
city: Bordeaux
country: France
facility: Institut Bergonie
city: Lyon
country: France
facility: Centre Leon Berard
city: Marseille
country: France
facility: CHU de la Timone
city: Cologne
country: Germany
facility: Medizinische Universitaetsklinik I at the University of Cologne
city: Dresden
country: Germany
facility: Universitatsklinikum Carl Gustav Carus
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Mannheim
country: Germany
facility: Klinikum der Stadt Mannheim
city: Munich
country: Germany
facility: Klinikum der Universitaet Muenchen - Grosshadern Campus
city: Tuebingen
country: Germany
facility: Southwest German Cancer Center at Eberhard-Karls-University
city: Amsterdam
country: Netherlands
facility: Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Nijmegen
country: Netherlands
facility: Universitair Medisch Centrum St. Radboud - Nijmegen
city: Rotterdam
country: Netherlands
facility: University Medical Center Rotterdam at Erasmus Medical Center
city: Bratislava
country: Slovakia
facility: National Cancer Institute - Bratislava
city: Barcelona
country: Spain
facility: Vall d'Hebron University Hospital
city: Madrid
country: Spain
facility: Hospital Universitario San Carlos
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust
state: England
city: Leeds
country: United Kingdom
facility: Leeds Cancer Centre at St. James's University Hospital
state: England
city: London
country: United Kingdom
facility: Royal Marsden - London
state: England
city: London
country: United Kingdom
facility: University College of London Hospitals
state: England
city: Newcastle-Upon-Tyne
country: United Kingdom
facility: Northern Centre for Cancer Treatment at Newcastle General Hospital
state: England
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
state: England
city: Sheffield
country: United Kingdom
facility: Cancer Research Centre at Weston Park Hospital
state: England
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
state: Scotland
city: Edinburgh
country: United Kingdom
facility: Edinburgh Cancer Centre at Western General Hospital
state: Scotland
city: Glasgow
country: United Kingdom
facility: Western Infirmary
state: Scotland
city: Glasgow
country: United Kingdom
facility: Gartnavel General Hospital
state: Scotland
Study officials:
affiliation: Institute of Cancer Research, United Kingdom
name: Ian R. Judson, MA, MD, FRCP
role: STUDY_CHAIR
References:
citation: Judson I, Verweij J, Gelderblom H, Hartmann JT, Schoffski P, Blay JY, Kerst JM, Sufliarsky J, Whelan J, Hohenberger P, Krarup-Hansen A, Alcindor T, Marreaud S, Litiere S, Hermans C, Fisher C, Hogendoorn PC, dei Tos AP, van der Graaf WT; European Organisation and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. Doxorubicin alone versus intensified doxorubicin plus ifosfamide for first-line treatment of advanced or metastatic soft-tissue sarcoma: a randomised controlled phase 3 trial. Lancet Oncol. 2014 Apr;15(4):415-23. doi: 10.1016/S1470-2045(14)70063-4. Epub 2014 Mar 5.