Multicohort Trial of Trabectedin and Low-dose Radiation Therapy in Advanced/Metastatic Sarcomas

Inclusion Criteria: 1. Patients must provide written informed consent prior to performance of study-specific procedures and must be willing to comply with treatment and follow up. Informed consent must be obtained prior to start of the screening process. Procedures conducted as part of the patient's routine clinical management (e.g. blood count, imaging tests, etc.) and obtained prior to signature of informed consent may be used for screening or baseline purposes as long as these procedures are conducted as specified in the protocol. 2. Age: 16-75 years. 3. Patients must have a diagnosis of soft tissue sarcoma (cohort A), bone tumors (osteosarcoma, chondrosarcoma) (cohort B) or small round-cell sarcomas (Ewing's sarcoma, rhabdomyosarcoma, desmoplastic small round-cell tumors and other small round cell sarcomas) (cohort C), with metastasis or locally advanced disease, and not suitable for metastasectomy or surgical resection or not oncologically recommended metastasectomy. A centralized diagnosis will be performed, and the central diagnosis confirmation will be mandatory prior to enrollment (tumor sample must be available and sent during screening). 4. Disease distribution allows meeting with normal tissue constraints of radiation therapy. Radiation oncologist must confirm this point, taking into account that the dose for extremities will be 45 Gy while for non-extremity will be 30 Gy. 5. Those lesions considered for radiation therapy must be related with a clinically relevant symptom. It is not necessary to irradiate all the lesions within one organ. Irradiating pulmonary lesions with infiltration of pleural serosa should be discouraged. 6. Patients must have documentation of disease progression within 6 months prior to study entry. 7. The patient must have been considered eligible for systemic chemotherapy. Patients should had received at least one line of systemic therapy (anthracycline-based in the case of Cohort A-STS, unless the patient is not candidate for treatment with anthracyclines), with a maximum of three previous lines for advanced/metastatic disease are allowed as long as trabectedin has not been included. 8. The following sarcoma types are eligible: * Soft tissue sarcoma * Bone tumors (osteosarcoma, chondrosarcoma) * Small round-cell sarcomas (Ewing's sarcoma, rhabdomyosarcoma, desmoplastic small round-cell tumors and other small round cell sarcomas) 9. Measurable disease, according to RECIST v1.1 criteria. 10. Performance status ≤ 1 (ECOG). 11. Adequate respiratory functions: FEV1 \> 1L; DLCO \> 40% (patients with pulmonary target lesions). 12. Adequate bone marrow function (hemoglobin ≥ 9 g/dL, leukocytes ≥ 3,000/mm3, absolute neutrophil count (ANC) ≥ 1,500/mm3, platelets ≥ 100,000/mm3). Patients with creatinine clearance (based on Cockroft and Gault) ≥30 ml/min, albumin ≥ 25 g/L, ALT and AST ≤ 2.5 times the ULN, total bilirubin ≤ ULN, CPK ≤ 2.5 times ULN, alkaline phosphatase ≤ 2.5 times the ULN are acceptable. If the increase of alkaline phosphatase is \> 2.5 times the ULN, then the alkaline phosphatase liver fraction and/or GGT must be ≤ ULN. 13. Men or women of childbearing potential must use an effective method of contraception before entry into the study and throughout the trial treatment and for 6 months after the last dose of trabectedin. Women of childbearing potential must have a negative urine pregnancy test before study entry. 14. Normal cardiac function with a LVEF ≥ 50% by echocardiogram or MUGA. 15. HBV and HCV serologies must be performed prior to enrollment. If HbsAg is positive it is recommended to reject the existence of replicative phase (HbaAg+, DNA VHB+). If these were positives the inclusion is not recommended, remaining at investigators' discretion the preventive treatment with lamivudine. If a potential patient is positive for anti-HCV antibodies, presence of the virus should be ruled out with a qualitative PCR, or the patient should NOT be included in the study (if a qualitative PCR cannot be performed then patient will not be able to enter the study) 16. Patient must have a central venous catheter for treatment, required for trabectedin administration. Exclusion Criteria: 1. Previous treatment with trabectedin or previous treatment with radiotherapy (this latter just in case the previous radiotherapy treatment does not allow the radiotherapy treatment of this study due to tissue constrains). 2. Liver inclusion in irradiation fields is not permitted, not even partially. 3. Normal tissue constrains for radiation therapy. 4. Performance status ≥ 2 (ECOG). 5. Plasma bilirubin \> ULN. 6. Creatinine clearance \<30ml/min. 7. History of other neoplastic disease with the exception of basal cell carcinoma or in situ cervical cancer adequately treated or no evidence of recurrence for more than 5 years after primary tumor treatment. 8. Severe chronic obstructive pulmonary disease (COPD) or other severe pulmonary diseases. 9. Significant cardiovascular disease (for example, dyspnea \> 2 NYHA). 10. Significant systemic diseases grade 3 or higher on the NCI-CTCAE v5.0 scale, that limit patient availability, or according to investigator judgment may contribute significantly to treatment toxicity. 11. Uncontrolled bacterial, mycotic or viral infections. 12. Known positive test for infection by human immunodeficiency virus (HIV). 13. Women who are pregnant or breast-feeding. 14. Psychological, familiar, social or geographic circumstances that limit the patient's ability to comply with the protocol or informed consent. 15. Patients who have participated in another clinical trial and/or have received any other investigational product in the last 30 days prior to enrollment. 16. Histologies other than those described in inclusion criteria.