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

NCT ID: NCT00002539

Last Updated: 2012-09-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

214 participants

Study Classification

INTERVENTIONAL

Study Start Date

1993-08-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Sarcoma

Keywords

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localized osteosarcoma

Study Design

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Allocation Method

RANDOMIZED

Primary Study Purpose

TREATMENT

Interventions

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filgrastim

Intervention Type BIOLOGICAL

cisplatin

Intervention Type DRUG

doxorubicin hydrochloride

Intervention Type DRUG

conventional surgery

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion 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
Maximum Eligible Age

40 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Medical Research Council

OTHER_GOV

Sponsor Role collaborator

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Marianne A. Nooij, MD

Role: STUDY_CHAIR

Leiden University Medical Center

Ian J. Lewis, MD

Role: STUDY_CHAIR

Leeds Cancer Centre at St. James's University Hospital

Locations

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Institut Jules Bordet

Brussels (Bruxelles), , Belgium

Site Status

Cliniques Universitaires Saint-Luc

Brussels (Bruxelles), , Belgium

Site Status

Universitair Ziekenhuis Antwerpen

Edegem, , Belgium

Site Status

U.Z. Gasthuisberg

Leuven, , Belgium

Site Status

Aarhus Kommunehospital

Aarhus, , Denmark

Site Status

Rigshospitalet

Copenhagen, , Denmark

Site Status

Centre Eugene Marquis

Rennes, , France

Site Status

Onze Lieve Vrouwe Gasthuis

Amsterdam, , Netherlands

Site Status

Emma Kinderziekenhuis

Amsterdam, , Netherlands

Site Status

Leiden University Medical Center

Leiden, , Netherlands

Site Status

University Medical Center Nijmegen

Nijmegen, , Netherlands

Site Status

Academisch Ziekenhuis Utrecht

Utrecht, , Netherlands

Site Status

Instituto Portugues de Oncologia de Francisco Gentil-Centro de Lisboa

Lisbon, , Portugal

Site Status

King Faisal Specialist Hospital and Research Centre

Riyadh, , Saudi Arabia

Site Status

Institute of Oncology, Ljubljana

Ljubljana, , Slovenia

Site Status

St. James's Hospital

Leeds, England, United Kingdom

Site Status

Countries

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Belgium Denmark France Netherlands Portugal Saudi Arabia Slovenia United Kingdom

References

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Lewis IJ, Nooij MA, Whelan J, Sydes MR, Grimer R, Hogendoorn PC, Memon MA, Weeden S, Uscinska BM, van Glabbeke M, Kirkpatrick A, Hauben EI, Craft AW, Taminiau AH; MRC BO06 and EORTC 80931 collaborators; European Osteosarcoma Intergroup. Improvement in histologic response but not survival in osteosarcoma patients treated with intensified chemotherapy: a randomized phase III trial of the European Osteosarcoma Intergroup. J Natl Cancer Inst. 2007 Jan 17;99(2):112-28. doi: 10.1093/jnci/djk015.

Reference Type RESULT
PMID: 17227995 (View on PubMed)

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.

Reference Type RESULT

Other Identifiers

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EOI-80931

Identifier Type: -

Identifier Source: secondary_id

EORTC-80931

Identifier Type: -

Identifier Source: secondary_id

MRC-BO06

Identifier Type: -

Identifier Source: secondary_id

EU-93024

Identifier Type: -

Identifier Source: secondary_id

EORTC-80931

Identifier Type: -

Identifier Source: org_study_id