Clinical trial: Mithramycin for Lung, Esophagus, and Other Chest Cancers (NCT01624090)

Eligibility criteria:
-  INCLUSION CRITERIA:

          -  Diagnosis: Patients with measurable inoperable, histologically confirmed primary 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

          -  Histologic confirmation of disease in the Laboratory of Pathology, Center for Cancer
             Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH).

          -  Disease amenable to biopsy via percutaneous approach or other minimally invasive
             procedures such as thoracoscopy, bronchoscopy, laparoscopy, or gastrointestinal (GI)
             endoscopy

          -  Age >18

          -  Eastern Cooperative Oncology Group (ECOG) status 0-2.

          -  Patients must have had or refused first-line standard chemotherapy for their
             inoperable malignancies.

          -  Patients must have had no chemotherapy, biologic therapy, or radiation therapy for
             their malignancy for at least 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 patient has recovered from any
             toxicity. At least 3 half-lives must have elapsed since monoclonal antibody treatment.
             At least six weeks must have elapsed between mitomycin C or nitrosourea treatment.

          -  Patients must have adequate organ and marrow function as defined below:

             a) Hematologic and Coagulation Parameters:

             i. Peripheral absolute neutrophil count (ANC) greater than or equal to 1500/mm^3

        ii. Platelets greater than or equal to 100,000/ mm^3 (transfusion independent)

        iii. Hemoglobin greater than or equal to 8 g/dL (peripheral red blood count (PRBC)
        transfusions permitted)

        iv. Prothrombin Time (PT)/Partial Thromboplastin Time (PTT) within normal limits (patient
        may be eligible for trial if abnormality is deemed clinically insignificant and cleared for
        protocol therapy by Hematology Consult Service)

        b) Hepatic Function

        i. Bilirubin (total) < 1.5 times upper limit of normal (ULN)

        ii. Alanine aminotransferase (ALT) (Serum glutamic pyruvic transaminase (SGPT)) less than
        or equal to 3.0 times ULN

        iii. Albumin > 2 g/dL

        c) Renal Function

        i. Creatinine within normal institutional limits or creatinine clearance greater than or
        equal to 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal.

        ii. Normal ionized calcium, magnesium and phosphorus (can be on oral supplementation)

          -  Cardiac Function: Left ventricular ejection fraction (EF) >40% by Echocardiogram,
             multi-gated acquisition scan (MUGA), or cardiac magnetic resonance (MR).

          -  Ability of subject to understand, and be willing to sign informed consent.

          -  Female and male patients (and when relevant their partners) must be willing to
             practice birth control (including abstinence) during and for two months after
             treatment, if of childbearing potential during sexual contact with a female of
             childbearing potential.

          -  Patients must be willing to undergo 2 tumor biopsies

        EXCLUSION CRITERIA:

          -  Patients with adenosine 5-triphosphate binding cassette subfamily B member 4 (ABCB4),
             adenosine 5-triphosphate binding cassette subfamily B member 11 (ABCB11),
             retinal-binding protein (RALBP) or cytochrome P851 (CYP851) genotypes associated with
             mithramycin-mediated hepatotoxicity.

          -  Clinically significant systemic illness (e.g. serious active infections or significant
             cardiac, pulmonary, hepatic or other organ dysfunction), that in the judgment of the
             Principal Investigator (PI) would compromise the patients ability to tolerate protocol
             therapy or significantly increase the risk of complications

          -  Patients with cerebral metastases

          -  Patients with any of the following pulmonary function abnormalities will be excluded:
             forced expiratory volume (FEV), < 30% predicted; diffusing capacity for carbon
             monoxide (DLCO), < 30% predicted (post-bronchodilator); Oxygen saturation greater than
             92% on room air. Arterial Blood Gas will be drawn if clinically indicated.

          -  Patients with evidence of active bleeding, intratumoral hemorrhage or history of
             bleeding diatheses, unless specifically occurring as an isolated incident during
             reversible chemotherapy induced thrombocytopenia

          -  Patients on therapeutic anticoagulation. Note: prophylactic anticoagulation (i.e.
             intraluminal heparin) for venous or arterial access devices is allowed

          -  Patients who are concurrently receiving or requiring any of the following agents,
             which may increase the risk for mithramycin related toxicities, such as hemorrhage:

               -  Thrombolytic agents

               -  Aspirin or salicylate-containing products, which may increase risk of hemorrhage

               -  Dextran

               -  Dipyridamole

               -  Sulfinpyrazone

               -  Valproic acid

               -  Clopidogrel

          -  Lactating or pregnant females (due to risk to fetus or newborn, and lack of testing
             for excretion in breast milk)

          -  Patients with history of Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV)
             or Hepatitis C Virus (HCV) due to potentially increased risk of mithramycin toxicity
             in this population

          -  Hypersensitivity to mithramycin

          -  Patients who in the opinion of the investigator may not be able to comply with the
             safety monitoring requirements of the study
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