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

Sarcoma Clinical Trial

Official title:

Randomised Trial Of Single Agent Doxorubicin Versus Doxorubicin Plus Ifosfamide In The First Line Treatment Of Advanced Or Metastatic Soft Tissue Sarcoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00061984
• Other study ID #: EORTC-62012
• Secondary ID: EORTC-62012
• Status: Completed
• Phase: Phase 3
• First received: June 5, 2003
• Last updated: October 24, 2014
• Start date: April 2003
• Est. completion date: July 2012

Study information

• Verified date: October 2014
• 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 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 455
• Est. completion date: July 2012
• Est. primary completion date: May 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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

Study Design

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Sarcoma

Intervention

Biological:
• pegfilgrastim

Drug:
• doxorubicin hydrochloride

• ifosfamide

Procedure:
• multimodality therapy

Locations

Country	Name	City	State
Austria	Karl-Franzens-University Graz	Graz
Belgium	Institut Jules Bordet	Brussels
Belgium	Universitair Ziekenhuis Antwerpen	Edegem
Belgium	U.Z. Gasthuisberg	Leuven
Canada	Tom Baker Cancer Centre - Calgary	Calgary	Alberta
Canada	Cross Cancer Institute at University of Alberta	Edmonton	Alberta
Canada	Margaret and Charles Juravinski Cancer Centre	Hamilton	Ontario
Canada	McGill Cancer Centre at McGill University	Montreal	Quebec
Canada	Doctor H. Bliss Murphy Cancer Centre	St. John's	Newfoundland and Labrador
Denmark	Aarhus Universitetshospital - Aarhus Sygehus	Aarhus
Denmark	Copenhagen County Herlev University Hospital	Copenhagen
France	Institut Bergonie	Bordeaux
France	Centre Leon Berard	Lyon
France	CHU de la Timone	Marseille
Germany	Medizinische Universitaetsklinik I at the University of Cologne	Cologne
Germany	Universitatsklinikum Carl Gustav Carus	Dresden
Germany	Universitaetsklinikum Essen	Essen
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Klinikum der Stadt Mannheim	Mannheim
Germany	Klinikum der Universitaet Muenchen - Grosshadern Campus	Munich
Germany	Southwest German Cancer Center at Eberhard-Karls-University	Tuebingen
Netherlands	Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital	Amsterdam
Netherlands	University Medical Center Groningen	Groningen
Netherlands	Leiden University Medical Center	Leiden
Netherlands	Universitair Medisch Centrum St. Radboud - Nijmegen	Nijmegen
Netherlands	University Medical Center Rotterdam at Erasmus Medical Center	Rotterdam
Slovakia	National Cancer Institute - Bratislava	Bratislava
Spain	Vall d'Hebron University Hospital	Barcelona
Spain	Hospital Universitario San Carlos	Madrid
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne
United Kingdom	Aberdeen Royal Infirmary	Aberdeen	Scotland
United Kingdom	Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust	Birmingham	England
United Kingdom	Edinburgh Cancer Centre at Western General Hospital	Edinburgh	Scotland
United Kingdom	Gartnavel General Hospital	Glasgow	Scotland
United Kingdom	Western Infirmary	Glasgow	Scotland
United Kingdom	Leeds Cancer Centre at St. James's University Hospital	Leeds	England
United Kingdom	Royal Marsden - London	London	England
United Kingdom	University College of London Hospitals	London	England
United Kingdom	Northern Centre for Cancer Treatment at Newcastle General Hospital	Newcastle-Upon-Tyne	England
United Kingdom	Derriford Hospital	Plymouth	England
United Kingdom	Cancer Research Centre at Weston Park Hospital	Sheffield	England

Sponsors (1)

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

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival			No
Secondary	Response as assessed by RECIST criteria			No
Secondary	Toxicity as assessed by CTC 2.0			Yes
Secondary	Treatment-related mortality			No