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Combination Chemotherapy and Surgery With or Without G-CSF in Treating Patients With Osteosarcoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00002539
Recruitment Status : Completed
First Posted : April 10, 2003
Last Update Posted : September 24, 2012
Medical Research Council
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC

Brief Summary:

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Colony-stimulating factors such as G-CSF may increase the number of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy. It is not yet known whether chemotherapy and surgery plus G-CSF is more effective than chemotherapy and surgery alone in treating patients with osteosarcoma.

PURPOSE: Randomized phase III trial to compare the effectiveness combination chemotherapy and surgery with or without G-CSF in treating patients who have newly diagnosed osteosarcoma.

Condition or disease Intervention/treatment Phase
Sarcoma Biological: filgrastim Drug: cisplatin Drug: doxorubicin hydrochloride Procedure: conventional surgery Phase 3

Detailed Description:


  • Determine the overall and disease-free survival of patients with newly diagnosed osteosarcoma of the extremity treated with conventional vs intensive cisplatin and doxorubicin with or without filgrastim (G-CSF) before and after definitive surgery.
  • Compare the toxicity of these regimens in these patients.
  • Compare the response in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive conventional doxorubicin (DOX) IV over 4 hours on days 1-3 and cisplatin (CDDP) IV continuously on day 1. Treatment continues every 3 weeks for 2 courses. At week 6, patients undergo amputation or local resection based on pretherapy imaging and response to chemotherapy. Beginning 2 weeks after surgery, patients receive 4 additional courses of conventional chemotherapy.
  • Arm II: Patients receive intensive DOX and CDDP as above on day 1 plus filgrastim (G-CSF) subcutaneously on days 4-13. Treatment continues every 2 weeks for 3 courses. At week 6, patients undergo definitive surgery as in arm I. Beginning 2 weeks after surgery, patients receive 3 additional courses of intensive DOX and CDDP with G-CSF.

Patients who experience disease progression during preoperative chemotherapy undergo surgery earlier than scheduled and complete all scheduled chemotherapy (6 courses) after surgery, at the discretion of the surgeon and oncologist. Within 4 weeks after limb-sparing procedure, patients with inadequate margins undergo amputation, followed 2 weeks later by chemotherapy.

Patients are followed monthly for 6 months, every 2 months for 6 months, every 3 months for 1 year, every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 500 patients will be accrued for this study.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 214 participants
Allocation: Randomized
Primary Purpose: Treatment
Study Start Date : August 1993
Actual Primary Completion Date : October 2002

Resource links provided by the National Library of Medicine

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 40 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically proven resectable osteosarcoma of the long bone of an extremity
  • No parosteal (juxtacortical), periosteal, Pagetoid, or post-irradiation sarcoma
  • No distant metastases



  • 40 and under

Performance status:

  • Not specified

Life expectancy:

  • Not specified


  • Neutrophil count at least 1,500/mm^3 OR
  • WBC at least 3,500/mm^3
  • Platelet count at least 100,000/mm^3


  • Bilirubin no greater than 1.2 mg/dL


  • Glomerular filtration rate at least 60 mL/min


  • No history of cardiac dysfunction


  • No other prior or concurrent malignancy except basal cell skin cancer OR
  • Carcinoma in situ of the cervix


Biologic therapy:

  • Not specified


  • No other concurrent chemotherapy

Endocrine therapy:

  • Not specified


  • See Disease Characteristics


  • See Disease Characteristics


  • No prior therapy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00002539

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Institut Jules Bordet
Brussels (Bruxelles), Belgium, 1000
Cliniques Universitaires Saint-Luc
Brussels (Bruxelles), Belgium, 1200
Universitair Ziekenhuis Antwerpen
Edegem, Belgium, B-2650
U.Z. Gasthuisberg
Leuven, Belgium, B-3000
Aarhus Kommunehospital
Aarhus, Denmark, DK-8000
Copenhagen, Denmark, 2100
Centre Eugene Marquis
Rennes, France, 35064
Onze Lieve Vrouwe Gasthuis
Amsterdam, Netherlands, 1091 HA
Emma Kinderziekenhuis
Amsterdam, Netherlands, NL-1100 DE
Leiden University Medical Center
Leiden, Netherlands, 2300 CA
University Medical Center Nijmegen
Nijmegen, Netherlands, NL-6500 HB
Academisch Ziekenhuis Utrecht
Utrecht, Netherlands, 3584 CX
Instituto Portugues de Oncologia de Francisco Gentil-Centro de Lisboa
Lisbon, Portugal, 1099-023 Codex
Saudi Arabia
King Faisal Specialist Hospital and Research Centre
Riyadh, Saudi Arabia, 11211
Institute of Oncology, Ljubljana
Ljubljana, Slovenia, Sl-1000
United Kingdom
St. James's Hospital
Leeds, England, United Kingdom, LS9 7TF
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Medical Research Council
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Study Chair: Marianne A. Nooij, MD Leiden University Medical Center
Study Chair: Ian J. Lewis, MD Leeds Cancer Centre at St. James's University Hospital

Publications of Results:
Lewis IJ, Nooij M: Chemotherapy at standard or increased dose intensity in patients with operable osteosarcoma of the extremity: a randomised controlled trial conducted by the European Osteo Sarcoma Intergroup (ISRCTN 86294690). [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-3281, 816, 2003.

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Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC Identifier: NCT00002539     History of Changes
Other Study ID Numbers: EORTC-80931
First Posted: April 10, 2003    Key Record Dates
Last Update Posted: September 24, 2012
Last Verified: September 2012
Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
localized osteosarcoma
Additional relevant MeSH terms:
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Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Liposomal doxorubicin
Antineoplastic Agents
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action