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

Sarcoma Clinical Trial

Official title:

A RANDOMISED TRIAL OF CHEMOTHERAPY WITH OR WITHOUT GRANULOCYTE COLONY-STIMULATING FACTOR IN OPERABLE OSTEOSARCOMA

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002539
• Other study ID #: EORTC-80931
• Secondary ID: EOI-80931EORTC-8
• Status: Completed
• Phase: Phase 3
• First received: November 1, 1999
• Last updated: September 20, 2012
• Start date: August 1993

Study information

• Verified date: September 2012
• 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 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 214
• Est. primary completion date: October 2002
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 40 Years

Eligibility

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

Study Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Osteosarcoma
• Sarcoma

Intervention

Biological:
• filgrastim

Drug:
• cisplatin

• doxorubicin hydrochloride

Procedure:
• conventional surgery

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires Saint-Luc	Brussels (Bruxelles)
Belgium	Institut Jules Bordet	Brussels (Bruxelles)
Belgium	Universitair Ziekenhuis Antwerpen	Edegem
Belgium	U.Z. Gasthuisberg	Leuven
Denmark	Aarhus Kommunehospital	Aarhus
Denmark	Rigshospitalet	Copenhagen
France	Centre Eugene Marquis	Rennes
Netherlands	Emma Kinderziekenhuis	Amsterdam
Netherlands	Onze Lieve Vrouwe Gasthuis	Amsterdam
Netherlands	Leiden University Medical Center	Leiden
Netherlands	University Medical Center Nijmegen	Nijmegen
Netherlands	Academisch Ziekenhuis Utrecht	Utrecht
Portugal	Instituto Portugues de Oncologia de Francisco Gentil-Centro de Lisboa	Lisbon
Saudi Arabia	King Faisal Specialist Hospital and Research Centre	Riyadh
Slovenia	Institute of Oncology, Ljubljana	Ljubljana
United Kingdom	St. James's Hospital	Leeds	England

Sponsors (2)

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

Countries where clinical trial is conducted

Belgium,  Denmark,  France,  Netherlands,  Portugal,  Saudi Arabia,  Slovenia,  United Kingdom, 

References & Publications (2)

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

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 his — View Citation