Clinical trial: Depsipeptide/Flavopiridol Infusion for Cancers of the Lungs, Esophagus, Pleura, Thymus or Mediastinum (NCT00094978)

Eligibility criteria:
-  INCLUSION CRITERIA:

               1. Patients with histologically or cytologically proven small cell or non-small cell
                  lung cancers, esophageal cancers, malignant pleural mesotheliomas chest wall
                  sarcoma, or epithelial thymomas are eligible for evaluation. In addition,
                  patients with cancers of nonthoracic origin with metastases to the lungs, pleura
                  or germ cell tumors refractory to standard therapy are eligible for evaluation.

               2. Chemo naive patients with inoperable lung and esophageal cancers, pleural
                  mesotheliomas, sarcoma, thymomas, as well as tumors of non-thoracic origin with
                  metastasis within the thorax may be eligible for study provided they have been
                  apprised of, and refused potentially effective first line chemotherapy.

               3. 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.

               4. Patients with prior Depsipeptide or Flavopiridol exposure are eligible for study
                  provided they have not experienced dose limiting toxicity at the dose of DP or
                  FLA that they are scheduled to receive.

               5. Patients must have had no chemotherapy, biologic therapy, or radiation therapy
                  for their malignancy for at least 30 days prior to treatment. At least six weeks
                  must elapse between mitomycin C or nitrosourea treatment and DP/FLA therapy.
                  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 patient has recovered from any toxicity.

               6. Patients must have an ECOG performance status of 0 - 2.

               7. 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.

               8. Patients must be 18 years of age or older due to the unknown effects of HDAC
                  inhibitors and cdk inhibitors during childhood and adolescent development.

               9. 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, and AST/ALT less than or equal to 1.5 times upper limit
                  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).

              10. 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.

        EXCLUSION CRITERIA:

          1. Patients with limited stage SCLC and operable NSCLC or operable esophageal cancer will
             be excluded.

          2. Patients with potentially treatable pulmonary metastases from lymphomas or germ cell
             tumors will be excluded.

          3. Patients who have received three or more systemic cytotoxic treatment regimens will be
             excluded due to possible cumulative marrow suppression.

          4. 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 to160/95).

             Myocardial infarction within one year of study.

             Clinically 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.

          5. Co-medication causing QTc prolongation (information at Appendix A and
             http://georgetowncert.org/gqdrugs_torsades.asp) unless a 5 half-life washout period
             has elapsed between discontinuing the drug and entering this study.

          6. Patients with active intracranial and leptomeningeal metastases, as well as those
             requiring anticonvulsant medications or steroids to control cerebral edema will be
             excluded.

          7. Patients with life expectancy less than three months will be excluded.

          8. Patients with pulmonary embolism or deep venous thrombosis requiring anticoagulation
             within six months of protocol entry will be excluded.

          9. Pregnant patients and nursing mothers will be excluded due to the unknown, potentially
             harmful effects of HDAC inhibitors and cdk inhibitors on fetal and early childhood
             development.

         10. Patients with active infections will be excluded.

         11. Patients with HIV infection will be excluded due to the potential risk of
             opportunistic infection during DP/FLA-induced myelosuppression and potentially
             deleterious activation of viral gene expression.

         12. Patients will have a screening 12 lead EKG and those patients with left ventricular
             hypertrophy will not be eligible.

         13. Patients who are taking hydrochlorothiazide (HCTZ) will have this agent stopped or
             switched to a potassium-conserving combination (e.g. Maxide or Dyazide) or other
             antihypertensive agent. Patients, who cannot have the agent stopped or switched to a
             potassium-conserving combination or other antihypertensive agent, will not be
             eligible.
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.


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? 1