Mesothelioma Clinical Trials Study of Gene Induction Mediated by Sequential Decitabine/Depsipeptide Infusion in Patients with Pulmonary and Pleural Malignancies This study is currently recruiting patients. Sponsored by For more information:National Cancer Institute (NCI)   Preliminary research indicates that the drug decitabine (DAC) enhances the immune response to tumors and may enable the p16 gene, called the 'suppressor gene,' to function normally. The drug depsipeptide (DP) appears to help kill cancer cells and prevent the growth of new cancer cells. These two drugs have been administered separately in the past. This study will examine the effect of the two drugs when they are given together. The study will enroll 42 patients with lung cancer. Pregnant or nursing women and patients with HIV will not be enrolled. An arterial blood gas test, an EKG, x-rays and scans, pulmonary function tests, HIV blood testing, and a baseline biopsy will be performed to determine patient eligibility. Each patient will receive up to two 34-day cycles of treatment with DAC and DP. The second cycle will begin 35 days after the first one ends. Patients who show improvement may be offered further treatments. Patients who experience severe adverse effects will be withdrawn from the study. A total of four tumor biopsies will be performed on each patient: one before treatment begins, one on day 5 of the first cycle, one before the second cycle, and one on day 5 of the second cycle. Depending on the location of the tumor, biopsies will be done either by bronchoscopy or needle aspiration. The drugs will be administered through a central venous catheter. Patients will be hospitalized for 5 to 6 days to receive the treatment. First, DAC will be administered for 72 hours. On day 4, DP will be given over a period of 4 hours. Different patients will receive different doses of DP to help determine safe doses. Frequent blood tests will be done to monitor the drugs' effects. Blood tests will also be done on days 8, 10, 11, 14, 18, 21, 28, and 34 of each cycle. Because DP affects the heart, patients will wear a heart monitor while receiving the first dose, and will have up to six EKGs during the first dose and up to four EKGs during the second dose. One month after each cycle, a follow-up x-ray, blood test, and scans of the chest, abdomen, pelvis, and brain will be done to help evaluate response to the treatment. Condition Treatment or Intervention Small Cell Carcinoma Mesothelioma Non-Small-Cell Lung Carcinoma  Drug: Decitabine  Drug: Depsipeptide This is a Phase I test In Phase I clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.   Study Type: Interventional Study Design: Treatment, Safety  Official Title: Phase I Study of Gene Induction Mediated by Sequential Decitabine/Depsipeptide Infusion in Patients with Pulmonary and Pleural Malignancies Further Study Details:  Previously we have demonstrated induction of tumor antigen and tumor suppressor gene expression in lung cancer cells following exposure to the DNA demethylating agent, Decitabine (DAC). We have also demonstrated that DAC mediated target gene expression and apoptosis can be significantly enhanced in cancer cells by subsequent exposure to the histone deacetylase (HDAC) inhibitor Depsipeptide FR901228 (DP). Furthermore, we have demonstrated that following DAC, or DAC/DP exposure, cancer cells can be recognized by cytolytic T cells specific for the cancer testis antigen, NY-ESO-1. On the basis of these data, a Phase I study was conducted to ascertain the maximum tolerated dose (MTD), pharmacokinetics and toxicity of continuous 72-hour intravenous Decitabine infusion, and to evaluate expression of several target genes which are known to be mediated by DNA demethylating agents in thoracic oncology patients. In addition, a Phase II study was initiated to evaluate clinical response and target gene induction in lung cancer patients following 4-hour Depsipeptide infusion. These trials were intended to lay the groundwork for this Phase I study evaluating gene induction in thoracic oncology patients mediated by sequential DAC/DP treatment. Patients with inoperable malignancies involving lungs or pleura will receive two cycles of 72-hour intravenous infusion of Decitabine followed by 4-hour Depsipeptide infusion using a Phase I study design. Decitabine will be administered by continuous infusion on days 1-4, and patient cohorts will receive escalating doses of Depsipeptide administered on day 4 and day 10 of a 34 day cycle. Pharmacokinetics, systemic toxicity, and response to therapy will be recorded. Tumor biopsies will be obtained prior to, and after therapy to evaluate expression of NY-ESO-1 tumor antigen, as well as p16 and p21 tumor suppressor genes which are known to be modulated by chromatin structure. Additional analysis will be undertaken to evaluate the extent of apoptosis in tumor tissues, and to determine if immune recognition of NY-ESO-1 can be demonstrated following sequential DAC/DP treatment. Results of these studies may provide the rationale for phase II evaluation of DAC/DP in thoracic oncology patients. Furthermore, results of the molecular analysis performed in this trial may support utilization of these agents in immunotherapy protocols specifically targeting cancer testis antigens, and provide the rationale for the use of DAC/DP as a means to augment the efficacy of additional cytotoxic agents in thoracic oncology patients. Genders Eligible for Study:  Both Criteria INCLUSION CRITERIA: Patients with histologically or cytologically proven primary small cell or non-small cell lung cancers, advanced esophageal cancer, or pleural mesotheliomas are eligible for evaluation. In addition, patients with cancers of nonthoracic origin with metastases to the lungs or pleura are eligible for evaluation. Patients with intracranial metastases which have been treated by surgery or radiation therapy may be eligible for study provided there is no evidence of active disease and no requirement for anticonvulsant therapy or steroids following treatment. Patients with prior Decitabine or Depsipeptide exposure are eligible for study provided they have not experienced dose limiting toxicity at the dose of DAC or DP that they are scheduled to receive. Patients must have had no chemotherapy, biologic therapy, or radiation therapy for their malignancy within 30 days prior to decitabine treatment. Patients may have received localized radiation therapy to non-target lesions provided that the radiotherapy is completed 14 days prior to commencing therapy, and the patients has recovered from any toxicity. Patients must have an ECOG performance status of 0-2. Patients must have adequate pulmonary reserve evidenced by FEV1 and DLCO greater than the 30% predicted, and pCO2 less than 50 mm Hg and pO2 greater than 60 mm Hg on room air ABG. Patients must be 18 years of age or older due to the unknown effects of demethylating agents and HDAC inhibitors during childhood and adolescent development. Patients must have a platelet count greater than 100, 000, an ANC equal to or greater than 1500 without transfusion or cytokine support, a normal PT, and adequate hepatic function as evidenced by a total bilirubin of less than 1.5 x upper limits of normal. Serum creatinine less than or equal to 1.6 mg/ml or the creatinine clearance must be greater than 70 ml/min/1.73m(2). Patients with a history of coronary artery disease, ventricular arrhythmias, myocardial infarction, or congestive heart failure, will have cardiology consultation. Subsequent evaluation will consist of stress/redistribution thallium, MUGA scan, or coronary angiography as indicated. Patients must be aware of the neoplastic nature of his/her illness, the experimental nature of the therapy, alternative treatments, potential benefits, and risks. The patient must be willing to sign an informed consent, and undergo tumor biopsies to evaluate target gene expression prior to, and after, decitabine/depsipeptide treatment. EXCLUSION CRITERIA: Patients with primary and metastatic cancers involving the lungs or pleura which cannot be readily biopsied by endoscopic or percutaneous fine needle aspiration techniques will be excluded. Patients with limited stage SCLC and operable NSCLC will be excluded. Patients who have received three or more systemic cytotoxic treatment regimens will be excluded due to possible cumulative marrow suppression. Patients with active intracranial and leptomeningeal metastases as well as those requiring anticonvulsant medications will be excluded. Patients with life expectancy less than three months will be excluded. Patients with pulmonary embolism, or deep venous thrombosis, or prosthetic heart valves requiring anticoagulation will be excluded. Cardiac exclusion criteria: Decompensated heart failure (NYHA Class III or IV); Myocardial infarction within one year of study; Uncontrolled arrhythmias; History of serious ventricular arrhythmias not controlled by coronary artery bypass surgery; QTc greater than 500msec; LVEF less than 40%; Co-medication causing QTc prolongation. Pregnant patients and lactating mothers will be excluded due to the unknown, potentially harmful effects of demethylating agents and HDAC inhibitors on fetal and early childhood development. Patients with active infections will be excluded. Patients with HIV infection will be excluded due to the potential risk of opportunistic infection during DAC/DP-induced myelosuppression and potentially deleterious activation of viral gene expression.