Continuous 24h Intravenous Infusion of Mithramycin, an Inhibitor of Cancer Stem Cell Signaling, in People With Primary Thoracic Malignancies or Carcinomas, Sarcomas or Germ Cell Neoplasms With Pleuropulmonary Metastases

Background: Increasing evidence indicates that activation of stem cell gene expression is a common mechanism by which environmental carcinogens mediate initiation and progression of thoracic malignancies. Similar mechanisms appear to contribute to extra-thoracic malignancies that metastasize to the chest. Utilization of pharmacologic agents, which target gene regulatory networks mediating "stemness" may be novel strategies for treatment of these neoplasms. Recent studies performed in the Thoracic Epigenetics Laboratory, National Cancer Institute (NCI), demonstrate that under exposure conditions potentially achievable in clinical settings, mithramycin diminishes stem cell gene expression and markedly inhibits growth of lung and esophageal cancer and malignant pleural mesothelioma (MPM) cells in vitro and in vivo. These findings add to other recent preclinical studies demonstrating impressive anti-tumor activity of mithramycin in epithelial malignancies and sarcomas that frequently metastasize to the thorax. Primary Objectives: * Phase I component: To determine pharmacokinetics, toxicities, and maximum tolerated dose (MTD) of mithramycin administered as a continuous 24h infusion in patients with primary thoracic malignancies or carcinomas, sarcomas or germ cell tumors metastatic to the chest. * Phase II component: To determine objective response rates (Complete Response (CR) + Partial Response (PR) of mithramycin administered as 24h intravenous infusions in patients with primary thoracic malignancies or carcinomas, sarcomas or germ cell tumors metastatic to the chest. Eligibility: * Patients with measurable inoperable, histologically confirmed lung and esophageal carcinomas, thymic neoplasms, germ cell tumors, malignant pleural mesotheliomas or chest wall sarcomas, as well as patients with gastric, colorectal or renal cancers and sarcomas metastatic to the thorax are eligible. * Patients with favorable germline single nucleotide polymorphisms (SNPs) in ATP Binding Cassette Subfamily B Member 4 (ABCB4), ATP Binding Cassette Subfamily B Member 11 (ABCB11), Ral binding protein (RALBP) or Cytochrome P450 Family 8 Subfamily B Member 1 (CYP8B1) that are associated with resistance to mithramycin-induced hepatotoxicity. * Patients must have had or refused first-line standard therapy for their malignancies. * Patients must be 18 years or older with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2, without evidence of unstable or decompensated myocardial disease. Patients must have adequate pulmonary reserve evidenced by forced expiratory volume (FEV1) and diffusing capacity for carbon monoxide (DLCO) equal to or greater than 30% predicted; Oxygen saturation \>= 92% on room air. ABG will be drawn if clinically indicated. * Patients must have a platelet count greater than or equal to 100,000, an absolute neutrophil count (ANC) equal to or greater than 1500 without transfusion or cytokine support, a normal prothrombin time (PT)/partial thromboplastin time (PTT), and adequate hepatic function as evidenced by a total bilirubin of \< 1.5 x upper limits of normal (ULN) and aspartate aminotransferase (AST)/alanine aminotransferase (ALT) \<= 3 X ULN. * Serum creatinine within normal institutional limits or creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal. Design: * Single arm Phase I dose escalation to define pharmacokinetics, toxicities and maximum tolerated dose (MTD). * Patient cohorts will receive 24hour(h) infusions of mithramycin targeting total doses previously administered during 7 daily six hour infusions at 30-50 mcg/kg. * The 24h infusions will be administered every 14 days (1 cycle). Four cycles will constitute one course of therapy. * Pharmacokinetics and toxicity assessment to define MTD will be assessed during Cycle 1 of the first course of therapy. * Due to uncertainties regarding potential cumulative toxicities, no intra-patient dose escalation will be allowed. * Once MTD has been defined, patients will be enrolled into two cohorts (primary thoracic malignancy vs neoplasm of non-thoracic origin metastatic to the chest) to determine clinical response rates at the MTD, using a Simon Optimal Two Stage Design for Phase II Clinical Trials targeting an objective response rate (Response Evaluation Criteria in Solid Tumors (RECIST) of 30%. * Following each course of therapy, patients will undergo restaging studies. Patients exhibiting objective response to therapy or stable disease by RECIST criteria will be offered an additional course of therapy. * Patients exhibiting disease progression will be removed from study. * Biopsies of index lesions will be obtained at baseline and on Day 4 of the first cycle of therapy for analysis of pharmacodynamic endpoints. Optional tumor biopsies may be requested at the completion of Course 1 (4 cycles) and in patients exhibiting objective responses.