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Doxorubicin With or Without Ifosfamide and Pegfilgrastim in Treating Patients With Locally Advanced or Metastatic Soft Tissue Sarcoma

Primary Purpose

Sarcoma

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
pegfilgrastim
doxorubicin hydrochloride
ifosfamide
multimodality therapy
Sponsored by
European Organisation for Research and Treatment of Cancer - EORTC
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sarcoma focused on measuring 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

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Karl-Franzens-University Graz
  • Institut Jules Bordet
  • Universitair Ziekenhuis Antwerpen
  • U.Z. Gasthuisberg
  • Tom Baker Cancer Centre - Calgary
  • Cross Cancer Institute at University of Alberta
  • Doctor H. Bliss Murphy Cancer Centre
  • Margaret and Charles Juravinski Cancer Centre
  • McGill Cancer Centre at McGill University
  • Aarhus Universitetshospital - Aarhus Sygehus
  • Copenhagen County Herlev University Hospital
  • Institut Bergonie
  • Centre Leon Berard
  • CHU de la Timone
  • Medizinische Universitaetsklinik I at the University of Cologne
  • Universitatsklinikum Carl Gustav Carus
  • Universitaetsklinikum Essen
  • Medizinische Hochschule Hannover
  • Klinikum der Stadt Mannheim
  • Klinikum der Universitaet Muenchen - Grosshadern Campus
  • Southwest German Cancer Center at Eberhard-Karls-University
  • Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
  • University Medical Center Groningen
  • Leiden University Medical Center
  • Universitair Medisch Centrum St. Radboud - Nijmegen
  • University Medical Center Rotterdam at Erasmus Medical Center
  • National Cancer Institute - Bratislava
  • Vall d'Hebron University Hospital
  • Hospital Universitario San Carlos
  • Centre Hospitalier Universitaire Vaudois
  • Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust
  • Leeds Cancer Centre at St. James's University Hospital
  • Royal Marsden - London
  • University College of London Hospitals
  • Northern Centre for Cancer Treatment at Newcastle General Hospital
  • Derriford Hospital
  • Cancer Research Centre at Weston Park Hospital
  • Aberdeen Royal Infirmary
  • Edinburgh Cancer Centre at Western General Hospital
  • Western Infirmary
  • Gartnavel General Hospital

Outcomes

Primary Outcome Measures

Overall survival

Secondary Outcome Measures

Response as assessed by RECIST criteria
Toxicity as assessed by CTC 2.0
Treatment-related mortality

Full Information

First Posted
June 5, 2003
Last Updated
October 24, 2014
Sponsor
European Organisation for Research and Treatment of Cancer - EORTC
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1. Study Identification

Unique Protocol Identification Number
NCT00061984
Brief Title
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

2. Study Status

Record Verification Date
October 2014
Overall Recruitment Status
Completed
Study Start Date
April 2003 (undefined)
Primary Completion Date
May 2010 (Actual)
Study Completion Date
July 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
European Organisation for Research and Treatment of Cancer - EORTC

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Masking
None (Open Label)
Allocation
Randomized
Enrollment
455 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Biological
Intervention Name(s)
pegfilgrastim
Intervention Type
Drug
Intervention Name(s)
doxorubicin hydrochloride
Intervention Type
Drug
Intervention Name(s)
ifosfamide
Intervention Type
Procedure
Intervention Name(s)
multimodality therapy
Primary Outcome Measure Information:
Title
Overall survival
Secondary Outcome Measure Information:
Title
Response as assessed by RECIST criteria
Title
Toxicity as assessed by CTC 2.0
Title
Treatment-related mortality

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ian R. Judson, MA, MD, FRCP
Organizational Affiliation
Institute of Cancer Research, United Kingdom
Official's Role
Study Chair
Facility Information:
Facility Name
Karl-Franzens-University Graz
City
Graz
ZIP/Postal Code
A-8010
Country
Austria
Facility Name
Institut Jules Bordet
City
Brussels
ZIP/Postal Code
1000
Country
Belgium
Facility Name
Universitair Ziekenhuis Antwerpen
City
Edegem
ZIP/Postal Code
B-2650
Country
Belgium
Facility Name
U.Z. Gasthuisberg
City
Leuven
ZIP/Postal Code
B-3000
Country
Belgium
Facility Name
Tom Baker Cancer Centre - Calgary
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4N2
Country
Canada
Facility Name
Cross Cancer Institute at University of Alberta
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 1Z2
Country
Canada
Facility Name
Doctor H. Bliss Murphy Cancer Centre
City
St. John's
State/Province
Newfoundland and Labrador
ZIP/Postal Code
A1B 3V6
Country
Canada
Facility Name
Margaret and Charles Juravinski Cancer Centre
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8V 5C2
Country
Canada
Facility Name
McGill Cancer Centre at McGill University
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3G 1Y6
Country
Canada
Facility Name
Aarhus Universitetshospital - Aarhus Sygehus
City
Aarhus
ZIP/Postal Code
DK-8000
Country
Denmark
Facility Name
Copenhagen County Herlev University Hospital
City
Copenhagen
ZIP/Postal Code
DK-2730
Country
Denmark
Facility Name
Institut Bergonie
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Facility Name
Centre Leon Berard
City
Lyon
ZIP/Postal Code
69373
Country
France
Facility Name
CHU de la Timone
City
Marseille
ZIP/Postal Code
13385
Country
France
Facility Name
Medizinische Universitaetsklinik I at the University of Cologne
City
Cologne
ZIP/Postal Code
D-50924
Country
Germany
Facility Name
Universitatsklinikum Carl Gustav Carus
City
Dresden
ZIP/Postal Code
D-01307
Country
Germany
Facility Name
Universitaetsklinikum Essen
City
Essen
ZIP/Postal Code
D-45122
Country
Germany
Facility Name
Medizinische Hochschule Hannover
City
Hannover
ZIP/Postal Code
D-30625
Country
Germany
Facility Name
Klinikum der Stadt Mannheim
City
Mannheim
ZIP/Postal Code
D-68135
Country
Germany
Facility Name
Klinikum der Universitaet Muenchen - Grosshadern Campus
City
Munich
ZIP/Postal Code
D-81377
Country
Germany
Facility Name
Southwest German Cancer Center at Eberhard-Karls-University
City
Tuebingen
ZIP/Postal Code
D-72076
Country
Germany
Facility Name
Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
City
Amsterdam
ZIP/Postal Code
1066 CX
Country
Netherlands
Facility Name
University Medical Center Groningen
City
Groningen
ZIP/Postal Code
9700 RB
Country
Netherlands
Facility Name
Leiden University Medical Center
City
Leiden
ZIP/Postal Code
2300 CA
Country
Netherlands
Facility Name
Universitair Medisch Centrum St. Radboud - Nijmegen
City
Nijmegen
ZIP/Postal Code
NL-6500 HB
Country
Netherlands
Facility Name
University Medical Center Rotterdam at Erasmus Medical Center
City
Rotterdam
ZIP/Postal Code
3000 CA
Country
Netherlands
Facility Name
National Cancer Institute - Bratislava
City
Bratislava
ZIP/Postal Code
833 10
Country
Slovakia
Facility Name
Vall d'Hebron University Hospital
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Universitario San Carlos
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
Centre Hospitalier Universitaire Vaudois
City
Lausanne
ZIP/Postal Code
CH-1011
Country
Switzerland
Facility Name
Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust
City
Birmingham
State/Province
England
ZIP/Postal Code
B15 2TH
Country
United Kingdom
Facility Name
Leeds Cancer Centre at St. James's University Hospital
City
Leeds
State/Province
England
ZIP/Postal Code
LS9 7TF
Country
United Kingdom
Facility Name
Royal Marsden - London
City
London
State/Province
England
ZIP/Postal Code
SW3 6JJ
Country
United Kingdom
Facility Name
University College of London Hospitals
City
London
State/Province
England
ZIP/Postal Code
WIT 3AA
Country
United Kingdom
Facility Name
Northern Centre for Cancer Treatment at Newcastle General Hospital
City
Newcastle-Upon-Tyne
State/Province
England
ZIP/Postal Code
NE4 6BE
Country
United Kingdom
Facility Name
Derriford Hospital
City
Plymouth
State/Province
England
ZIP/Postal Code
PL6 8DH
Country
United Kingdom
Facility Name
Cancer Research Centre at Weston Park Hospital
City
Sheffield
State/Province
England
ZIP/Postal Code
S1O 2SJ
Country
United Kingdom
Facility Name
Aberdeen Royal Infirmary
City
Aberdeen
State/Province
Scotland
ZIP/Postal Code
AB25 2ZN
Country
United Kingdom
Facility Name
Edinburgh Cancer Centre at Western General Hospital
City
Edinburgh
State/Province
Scotland
ZIP/Postal Code
EH4 2XU
Country
United Kingdom
Facility Name
Western Infirmary
City
Glasgow
State/Province
Scotland
ZIP/Postal Code
G11 6NT
Country
United Kingdom
Facility Name
Gartnavel General Hospital
City
Glasgow
State/Province
Scotland
ZIP/Postal Code
G12 0YN
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
24618336
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.
Results Reference
derived

Learn more about this trial

Doxorubicin With or Without Ifosfamide and Pegfilgrastim in Treating Patients With Locally Advanced or Metastatic Soft Tissue Sarcoma

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