Metronomic Chemotherapy in Patients With Advanced Solid Tumor With Bone Metastasis and Advanced Pretreated Osteosarcoma

Inclusion Criteria: 1. Histology: * Advanced solid tumor with radiologically proven bone metastasis, (dose escalation part) * Patients with osteogenic osteosarcoma (dose escalation part and expansion cohort) histologically confirmed by central review 2. Metastatic or unresectable locally advanced disease, not eligible for alternative local treatment (radiotherapy for instance) 3. Age \> 18 years for patients with solid tumor and ≥ 13 years for patients with osteosarcoma 4. ECOG, performance status ≤ 1 5. Life expectancy \> 3 months 6. Measurable disease according to RECIST v1.1. At least one site of disease must be uni-dimensionally ≥ 10 mm 7. Patients must have histologically confirmed diagnosis of locally advanced and/or metastatic solid tumors, which are not amenable to standard treatment, including for patients with osteosarcoma conventional agents such as anthracyclines, platinum salts, ifosfamide and/or methotrexate 8. At least three weeks since last chemotherapy, immunotherapy or any other pharmacological treatment and/or radiotherapy 9. Adequate haematological, renal, metabolic and hepatic function: * Haemoglobin ≥ 10 g/dl (patients may have received prior red blood cell transfusion, if clinically indicated); leucocytes ≥ 3 x 10\^9/l, absolute neutrophil count ≥ 1.5 x 10\^9/l, and platelet count ≥ 120 x 10\^9/l. * Alanine aminotransferase and aspartate aminotransferase ≤ 2.5 x upper limit of normality (ULN) * Total bilirubin ≤ 1.5 x ULN * Calculated creatinine clearance \> 40 ml/min/1.73 m² (according to MDRD formula) * Creatine phosphokinase ≤ 2.5 x ULN * Albumin \> 25 g/l 10. No prior or concurrent malignant disease diagnosed or treated in the last 2 years except adequately treated in situ carcinoma of the cervix, basal or squamous skin cell carcinoma, or in situ transitional bladder cell carcinoma, 11. Recovery to grade ≤ 1 from any adverse event derived from previous treatment (excluding alopecia of any grade and non-painful peripheral neuropathy grade ≤ 2) according to the NCI-CTCAE, version 4 12. Patients with a French social security in compliance with the French law relating to biomedical research 13. Voluntarily signed and dated written informed consent prior to any study specific procedure 14. Women of childbearing potential must have a negative serum pregnancy test before study entry. Both women and men must agree to use a medically acceptable method of contraception throughout the treatment period and for six months after discontinuation of treatment Exclusion Criteria: 1. Previous treatment with sirolimus 2. Concomitant diseases/conditions: * Clinically significant and/or rapidly accumulating ascites, pericardial and/or pleural effusions * Unstable cardiac disease, pulse oximetry saturation \< 90% at rest * Clinically significant immunodeficiency, such as HIV or active Hepatitis B or C * History of auto-immune disease, transplantation 3. Central nervous system malignancy 4. Men or women of childbearing potential who are not using an effective method of contraception; women who are pregnant or breast feeding 5. Patients receiving any substances that are inhibitors or inducers of CYP450 3A4 6. Ongoing or recent (\<6 weeks) dental problem, including any severe tooth or jaw infection (mandible and maxilla), dental trauma, dental or stomatological surgery (implants). Current dental cares are allowed 7. History of maxillary osteonecrosis or delayed healing after dental surgery 8. Participation to a study involving a medical or therapeutic intervention in the last 30 days 9. Previous enrolment in the present study 10. Patient unable to follow and comply with the study procedures because of any geographical, familial, social or psychological reasons 11. Known hypersensitivity to any involved study drug or any of its formulation components 12. Patients receiving live vaccines within 30 days prior to the first dose of study therapy and while participating in study