Clinical trial: Phase I Study of Gene Induction Mediated by Sequential Decitabine/Depsipeptide Infusion With or Without Concurrent Celecoxib in Subjects With Pulmonary and Pleural Malignancies (NCT00037817)

Eligibility 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 with prior or current celecoxib exposure are eligible for study provided that it
        has been intermittent, or of short term duration (less than 1 month).

        Patients must have had no chemotherapy, biologic therapy, celecoxib exposure, or radiation
        therapy for their malignancy within 30 days prior to 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).

        All patients will have cardiology consultation. Subsequent evaluation will consist of
        stress/redistribution thallium, 24th ambulatory EKG monitoring, ECHO, cardiac MR, 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 untreated limited stage SCLC, and operable NSCLC or operable esophageal
        cancer 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, patients with known cardiac abnormalities such as:

        -Uncontrolled arrhythmias

        History of serious ventricular arrhythmias not controlled by coronary artery bypass
        surgery.

        Patients with a history of sustained VT, VF, Toursades de Pointes, or cardiac arrest who do
        not have an automatic implantable cardioverter defibrillator in place

        Congenital Long QT syndrome or QTc greater than 480 msec

        Patients with Mobitz II second degree block who do not have a pacemaker

        Patients with any cardiac arrhythmia requiring anti-arrhythmic medication other than a beta
        blocker or calcium channel blocker

        Patients in whom digitalis cannot be discontinued

          -  Decompensated heart failure (NYHA Class II or IV)

          -  LVEF less than 50% by MUGA scan or echocardiogram

          -  Hypertrophic or restrictive cardiomyopathy from prior treatment of other causes and
             patients with left ventricular hypertrophy

          -  Uncontrolled hypertension (i.e greater than or equal to 160/95)

          -  Myocardial infarction within one year of study

          -  Clinical significant active myocardial ischemia on the basis of nuclear imaging or
             angiography

          -  History of coronary artery disease (e.g. angina Canadian Class II-Iv or positive
             stress imaging study)

          -  Patients with other cardiac disease may be excluded at the discretion of the PI
             following consultation with cardiology

        Co-medication causing QTc prolongation unless a 5 half-life washout period has elapsed
        between discontinuing the drug and entering this study.

        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.

        Patients should not be using hydrochlorothiazide diuretics if entered on this protocol.
        Therefore, patients who must use hydrochlorothiazide diuretics will be excluded.
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 18 Years old.
Subject must be at most 65 Years

Patient description (medical language): A 61-year-old man comes to the clinic due to nonproductive cough and progressive dyspnea.  The patient's medical conditions include hypertension, hypercholesteremia and peptic ulcer disease.  He smokes 2 packs of cigarettes daily for the past 30 years.  On examination, there are decreased breath sounds and percussive dullness at the base of the left lung.  Other vital signs are normal. Abdomen is soft without tenderness. CT scan shows a left-sided pleural effusion and nodular thickening of the pleura. The plural fluid was bloody on thoracentesis. Biopsy shows proliferation of epithelioid-type cells with very long microvilli.

Patient description (patient's own words): I am 61 and I had to go to the clinic because I couldn't stop coughing and I experienced some breath shortness. I suffer from hypertension and cholesterol and I also have a stomach ulcer. I should admit that I've been smoking 2 packs of cigarettes every day for the past 30 years. My doctor told me that my breath in my left lung sounds bad. But he told me that my blood pressure, heart rate, breathing rate and temperature are normal. My belly is also normal. However my X-Rays show some liquid on the left side and a mass where the liquid got hard. The scary thing is that the liquid was bloody when they got it out. They did a biopsy and it showed that I have an increase of epithelioid-type cells with very long microvilli.

Does the patient match the trial criteria? Entailment