European Study in Bone Sarcoma Patients Over 40 Years

Study Overview
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Brief Summary
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The study is a first step of a process to establish the standard chemotherapy treatment with the aim to improve outcome for patients with these rare tumours. For this reason the study will be non-controlled clinical trial. In this regard, the study aims to determine the feasibility of intensive chemotherapy in this age group, and/or separate efficacy analyses according to the different histologic categories and whether the number of patients recruited by the co-operating groups permits future randomised studies.

Detailed Description
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Wide surgical removal of the tumor with the addition of a systemic treatment based on the antineoplastic drugs active against osteosarcoma (Adriamycin, Cisplatin, Ifosfamide, Methotrexate). The use of radiation therapy will be given to patients with unresectable tumors. It is recommended in patients who underwent inadequate surgical removal of the tumor. The addition of radiation therapy can not compensate for an adequate surgical treatment. All the patients eligible for the study will receive the planned systemic treatment. Depending on clinical features, and feasibility of adequate surgical removal of the tumor, patients may receive primary chemotherapy followed by a postoperative chemotherapy treatment or only an adjuvant chemotherapy. In case of immediate surgery, patients will receive an adjuvant treatment with the 3-drug regimen (Cisplatin-Adriamycin-Ifosfamide).

Official Title
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A European Treatment Protocol for Bone-sarcoma in Patients Older Than 40 Years

Conditions
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Spindle Cell Sarcoma of Bone, Osteosarcoma

Intervention / Treatment
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* Drug: Doxorubicin+cisplatin+ifosfamide
* Drug: Doxorubicin+cisplatin+ifosfamide+methotrexate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven diagnosis of high-grade sarcoma of bone of any site. Histologic types: osteosarcoma (high-grade surface, central primary and secondary), fibrosarcoma, malignant fibrous histiocytoma, leiomyosarcoma, dedifferentiated chondrosarcoma, angiosarcoma. Age: 41 - 65 Normal bone marrow, hepatic, cardiac and renal function Absence of contraindications to the use of cisplatin, adriamycin, and ifosfamide Written informed consent Exclusion Criteria: Planned chemotherapy and/or follow-up not feasible Previous chemotherapy treatment, which contraindicates the use of one or more drugs, included in the present protocol Previous chemotherapy treatment for the current tumor White blood count < 3.0 x 109/L, and platelets < 100 x 109/L Creatinine clearance < 70 ml/min Left ventricular ejection fraction < 55% or fractional shortening rate of the left ventricle <28% Serum transaminases and bilirubin > 2 times the normal values ECOG performance status > 2 Chondrosarcoma or small/round cell bone sarcoma including mesenchymal chondrosarcoma and Ewing's family tumors.

Ages Eligible for Study
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Minimum Age: 41 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Chemotherapy for Good responder<br>Doxorubicin + cisplatin + ifosfamide Pre-operative and post-operative chemotherapy for patients with good responder high grade osteosarcoma | Drug: Doxorubicin+cisplatin+ifosfamide<br>* Chemotherapy for Good responder high grade osteosarcoma<br>* Other names: Doxorubicin,cisplatin,ifosfamide;|
| Chemotherapy for Poor responder<br>Doxorubicin+cisplatin+ifosfamide+methotrexate Pre-operative and post-operative chemotherapy for patients with poor responder high grade osteosarcoma | Drug: Doxorubicin+cisplatin+ifosfamide+methotrexate<br>* Chemotherapy for Poor responder high grade osteosarcoma<br>* Other names: Doxorubicin,cisplatin,ifosfamide,methotrexate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event-free survival | Survival without any events related to disease (e.g: progression, relapse or osteosarcoma related death) | from the date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 168 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | Survival without progression of disease | from the date of randomization until the date of first documented progression of disease, whichever came first, assessed every 6 months, up to 168 months | 
| Disease-free survival | Survival without disease | from the date of randomization until the date of first documented progression of disease, whichever came first, assessed every 6 months, up to 168 months | 
| Metastasis-free survival | Survival without metastasis | from the date of randomization until the date of first documented progression in term of metastasis, whichever came first, assessed every 3 months, up to 168 months | 
| Overall survival | Global patients survival evaluation after treatment | from the date of randomization until the end of the study, assessed every 3 months, up to 168 month | 
| Chemotherapy toxicity | Number and grade of adverse events related to the study treatments | Every 3 weeks |