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

This study has been completed.
Sponsor:
Collaborator:
Medical Research Council
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier:
NCT00002539
First received: November 1, 1999
Last updated: September 20, 2012
Last verified: September 2012
  Purpose

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 Intervention Phase
Sarcoma
Biological: filgrastim
Drug: cisplatin
Drug: doxorubicin hydrochloride
Procedure: conventional surgery
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Primary Purpose: Treatment
Official Title: A RANDOMISED TRIAL OF CHEMOTHERAPY WITH OR WITHOUT GRANULOCYTE COLONY-STIMULATING FACTOR IN OPERABLE OSTEOSARCOMA

Resource links provided by NLM:


Further study details as provided by European Organisation for Research and Treatment of Cancer - EORTC:

Enrollment: 214
Study Start Date: August 1993
Primary Completion Date: October 2002 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • 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.

  Eligibility

Ages Eligible for Study:   up to 40 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

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

PATIENT CHARACTERISTICS:

Age:

  • 40 and under

Performance status:

  • Not specified

Life expectancy:

  • Not specified

Hematopoietic:

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

Hepatic:

  • Bilirubin no greater than 1.2 mg/dL

Renal:

  • Glomerular filtration rate at least 60 mL/min

Cardiovascular:

  • No history of cardiac dysfunction

Other:

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

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Not specified

Chemotherapy:

  • No other concurrent chemotherapy

Endocrine therapy:

  • Not specified

Radiotherapy:

  • See Disease Characteristics

Surgery:

  • See Disease Characteristics

Other:

  • No prior therapy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00002539

Locations
Belgium
Cliniques Universitaires Saint-Luc
Brussels (Bruxelles), Belgium, 1200
Institut Jules Bordet
Brussels (Bruxelles), Belgium, 1000
Universitair Ziekenhuis Antwerpen
Edegem, Belgium, B-2650
U.Z. Gasthuisberg
Leuven, Belgium, B-3000
Denmark
Aarhus Kommunehospital
Aarhus, Denmark, DK-8000
Rigshospitalet
Copenhagen, Denmark, 2100
France
Centre Eugene Marquis
Rennes, France, 35064
Netherlands
Emma Kinderziekenhuis
Amsterdam, Netherlands, NL-1100 DE
Onze Lieve Vrouwe Gasthuis
Amsterdam, Netherlands, 1091 HA
Leiden University Medical Center
Leiden, Netherlands, 2300 CA
University Medical Center Nijmegen
Nijmegen, Netherlands, NL-6500 HB
Academisch Ziekenhuis Utrecht
Utrecht, Netherlands, 3584 CX
Portugal
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
Slovenia
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
Investigators
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
  More Information

Additional Information:
Publications:
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.

Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT00002539     History of Changes
Other Study ID Numbers: EORTC-80931, EOI-80931, EORTC-80931, MRC-BO06, EU-93024
Study First Received: November 1, 1999
Last Updated: September 20, 2012
Health Authority: United States: Federal Government

Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
localized osteosarcoma

Additional relevant MeSH terms:
Osteosarcoma
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Sarcoma
Doxorubicin
Liposomal doxorubicin
Lenograstim
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 16, 2014