Phase II, multicenter, randomized, open-label study with MAP +/- denosumab regimen for the treatment of patients with metastatic osteosarcoma

INTERVENTION: Product Name: CISPLATINO Product Code: [CISPLATINO] Pharmaceutical Form: Solution for infusion in administration system INN or Proposed INN: CISPLATINO CAS Number: 15663‐27‐1 Current Sponsor code: CDP Other descriptive name: CISPLATIN Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 100‐ Trade Name: XGEVA ‐ 120 MG ‐ SOLUZIONE INIETTABILE ‐ USO SOTTOCUTANEO ‐ FLACONCINO (VETRO) ‐ 1.7 ML 1 FLACONCINO Product Name: DENOSUMAB Product Code: [DENOSUMAB] Pharmaceutical Form: Solution for injection INN or Proposed INN: DENOSUMAB CAS Number: 615258‐40‐7 Current Sponsor code: DENOSUMAB Other descriptive name: DENOSUMAB Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 120‐ Product Name: METHOTREXATE Product Code: [METHOTREXATE] Pharmaceutical Form: Solution for injection INN or Proposed INN: METHOTREXATE CAS Number: 59‐05‐2 Current Sponsor code: METHOTREXATE Other descriptive name: METHOTREXATE Concentration unit: mg/ml milligram(s)/millilitre Concentration type: range Concentration number: 10‐500 Product Name: DOXORUBICINA Product Code: [ADM] Pharmaceutical Form: Concentrate and solvent for solution for infusion INN or Proposed INN: DOXORUBICINA CLORIDRATO CAS Number: 914‐00‐1 Current Sponsor code: ADM Other descriptive name: DOXORUBICIN Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 2‐ CONDITION: Metastatic osteosarcoma ; MedDRA version: 21.1 Level: PT Classification code 10031294 Term: Osteosarcoma metastatic System Organ Class: 10029104 ‐ Neoplasms benign, malignant and unspecified (incl cysts and polyps) Therapeutic area: Diseases [C] ‐ Cancer [C04] PRIMARY OUTCOME: Main Objective: Evaluation of the effectiveness of denosumab in combination with standard chemotherapy in patients with metastatic OS. Primary end point(s): 5‐year Event Free Survival ‐ EFS Secondary Objective: ‐ Overall Survival: OS; ‐ Safety and toxicity of combination treatment; ‐ Evaluation of RANK/RANKL expression, of tumor inflammatory infiltrate, both in the primitive tumor and in the metastatic sites reallocated, at diagnosis and after therapy, correlated with the treatment and response to the treatment received Timepoint(s) of evaluation of this end point: 5 years INCLUSION CRITERIA: ‐ High‐grade metastatic osteosarcoma ‐ Age at diagnosis = 12 years (or with skeletal maturity) and = 40 years ‐ ECOG Performance status = 2 or Lansky = 40% ‐ Adequate medullary, cardiac, liver and kidney function ‐ Female subjects of childbearing age must perform a pregnancy test before entering the study ‐ Written informed consent obtained from the patient/parent/legal representative Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 56 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range