Immune Changes Following Trabectedin in Patients With Metastatic or Unresectable Sarcoma

Inclusion Criteria: * Subjects must have a diagnosis of advanced (unresectable or metastatic) sarcoma, for which trabectedin treatment is indicated * Subjects must have received prior anthracycline treatment; subjects who failed to tolerate it or for whom it is not clinically appropriate in the opinion of their treating physician may be included * All ongoing toxicities related to prior therapy must be resolved to grade 1 or better (except alopecia) * Total bilirubin level =\< upper limit of normal (ULN) mg/dL * Aspartate aminotransferase (AST) =\< 2.5 x ULN * Alanine aminotransferase (ALT) =\< 2.5 x ULN * Alkaline phosphatase \< 2.5 x ULN * Serum creatinine =\< 1.5 x ULN * Calculated creatinine clearance \>= 30 mL/min using the Cockcroft-Gault formula may be included * Creatine phosphokinase (CPK) =\< 2.5 x ULN * Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L * Platelet count \>= 100 x 10\^9/L * Hemoglobin \>= 9 g/dL * Baseline left ventricular ejection fraction (LVEF) 45% or greater (by echocardiogram or multigated acquisition scan \[MUGA\] study) and no evidence of New York Heart Association class ll to IV heart failure * Subjects with lesions safely accessible for biopsy, in the opinion of the treating physician and/or interventional radiology * Male or non-pregnant and non-breast feeding female: * Females of child-bearing potential must agree to use highly effective contraception without interruption from initiation of therapy and while on study medication and have a negative serum pregnancy test (beta-human chorionic gonadotropin \[hCG\]) result at screening and agree to ongoing pregnancy testing during the course of the study, and at the end of study treatment; a highly effective method of contraception is defined as one that results in a low failure rate (that is, \< 1% per year), when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some intrauterine contraceptive devices, sexual abstinence, or a vasectomized partner * Male subjects must practice abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study * Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 * Ability to understand and sign informed consent * Willingness and ability to comply with scheduled visits, laboratory tests, and other study procedures Exclusion Criteria: * Subjects for whom treatment with trabectedin is not indicated * All subjects with brain metastases, except those meeting the following criteria: * Brain metastases that have been treated locally and are clinically stable for at least 2 weeks prior to enrollment * No ongoing neurological symptoms that are related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable) * Subjects must be either off steroids or on a stable or decreasing dose of =\< 10 mg daily prednisone (or equivalent), excluding dexamethasone given as pre-treatment for trabectedin * Prior organ transplantation, including allogeneic stem cell transplantation * Subjects with abnormal prothrombin time (PT)/international normalized ratio (INR)/partial thromboplastin time (PTT) or bleeding diathesis * Prior treatment with trabectedin * Prior chemotherapy within 2 weeks; prior immunotherapy or biologic therapy within 4 weeks; prior radiation therapy within 3 weeks * Significant acute or chronic infections as these may affect the immune response including: * Known history of testing positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) * Positive test for hepatitis B virus (HBV) surface antigen and / or confirmatory hepatitis C virus (HCV) ribonucleic acid (RNA) (if anti-HCV antibody tested positive) * Subjects on chronic therapy with any systemic immunosuppressant (not counting inhaled steroids or steroid creams) for any reason, including autoimmune disease * Known alcohol or drug abuse * Subjects who are breast feeding * Subjects with known hypersensitivity including anaphylaxis to trabectedin * Myocardial infarction (infarct) within 6 months before enrollment, New York Heart Association (NYHA) class II or greater heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, clinically significant pericardial disease, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities