Clinical trial NCT00002539: Combination Chemotherapy and Surgery With or Without G-CSF in Treating Patients With Osteosarcoma
Official title: A RANDOMISED TRIAL OF CHEMOTHERAPY WITH OR WITHOUT GRANULOCYTE COLONY-STIMULATING FACTOR IN OPERABLE OSTEOSARCOMA
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Sarcoma
Keywords: localized osteosarcoma
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
Collaborators: name: Medical Research Council
First posted: 2003-04-10
Enrollment: 214
Sex: ALL
Maximum age (years): 40
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Brussels (Bruxelles)
country: Belgium
facility: Institut Jules Bordet
city: Brussels (Bruxelles)
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Leuven
country: Belgium
facility: U.Z. Gasthuisberg
city: Aarhus
country: Denmark
facility: Aarhus Kommunehospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Rennes
country: France
facility: Centre Eugene Marquis
city: Amsterdam
country: Netherlands
facility: Onze Lieve Vrouwe Gasthuis
city: Amsterdam
country: Netherlands
facility: Emma Kinderziekenhuis
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Nijmegen
country: Netherlands
facility: University Medical Center Nijmegen
city: Utrecht
country: Netherlands
facility: Academisch Ziekenhuis Utrecht
city: Lisbon
country: Portugal
facility: Instituto Portugues de Oncologia de Francisco Gentil-Centro de Lisboa
city: Riyadh
country: Saudi Arabia
facility: King Faisal Specialist Hospital and Research Centre
city: Ljubljana
country: Slovenia
facility: Institute of Oncology, Ljubljana
city: Leeds
country: United Kingdom
facility: St. James's Hospital
state: England
Study officials:
affiliation: Leiden University Medical Center
name: Marianne A. Nooij, MD
role: STUDY_CHAIR
affiliation: Leeds Cancer Centre at St. James's University Hospital
name: Ian J. Lewis, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.