The Online Asbestos, Asbestos Cancer, & Mesothelioma Authority

Clinical Trials

Further study details as provided by National Cancer Institute (NCI):

Estimated Enrollment: Â	48
Study Start Date: Â	November 2004
Estimated Primary Completion Date: Â	November 2005 (Final data collection date for primary outcome measure)

Detailed Description:

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed advanced malignancy of 1 of the following types:
  • Primary small cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC)
    • No limited-stage SCLC or operable NSCLC
  • Esophageal cancer
    • Inoperable disease
  • Malignant pleural mesothelioma
  • Epithelial thymoma
  • Cancer of nonthoracic origin with metastases to the lungs or pleura
    • No potentially treatable pulmonary metastases from lymphomas or germ cell tumors
• Tumor must be amenable to biopsy by endoscopic or percutaneous fine needle aspiration techniques
• Chemonaïve patients allowed provided they refused potentially effective first-line chemotherapy
• Intracranial or leptomeningeal metastases allowed provided the following are true:
  • Treated by surgery or radiotherapy
  • No evidence of active disease
  • No requirement for anticonvulsant therapy or steroids

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 3 months

Hematopoietic

• Platelet count > 100,000/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3 (transfusion and cytokine independent)

Hepatic

• PT normal
• Bilirubin < 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 1.5 times ULN

Renal

• Creatinine ≤ 1.6 mg/dL OR
• Creatinine clearance > 70 mL/min

Cardiovascular

• No myocardial infarction within the past 6 months
• Ejection fraction ≥ 45%
• QTc ≤ 500 msec
• No unstable angina
• No cardiac ischemia
• No left ventricular hypertrophy
• No deep venous thrombosis requiring anticoagulation within the past 6 months
• No known cardiac abnormalities including any of the following:
  • Uncontrolled arrhythmias
  • History of sustained ventricular tachycardia, ventricular fibrillation, Torsades de Pointes, or cardiac arrest without an automatic implantable cardioverter defibrillator in place
  • Congenital long QT syndrome or QTc > 480 msec
  • Mobitz II second degree block without a pacemaker in place
  • Any cardiac arrhythmia requiring antiarrhythmic medication
    • Beta blockers and calcium channel blockers allowed
  • New York Heart Association class II or IV decompensated heart failure
  • Left ventricular ejection fraction < 50% by MUGA scan or echocardiogram
  • Hypertrophic or restrictive cardiomyopathy from prior treatment or other causes
  • Left ventricular hypertrophy
  • Uncontrolled hypertension (i.e., blood pressure ≥ 160/95)
  • Myocardial infarction within the past year
  • Clinically significant active myocardial ischemia by nuclear imaging or angiography
  • History of coronary artery disease (e.g., Canadian class II-IV angina or positive stress imaging study)

Pulmonary

• FEV_1 and DLCO > 30% of predicted
• pCO_2 < 50 mm Hg by arterial blood gas (ABG) on room air
• pO_2 > 60 mm Hg by ABG on room air
• No pulmonary embolism requiring anticoagulation within the past 6 months

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active infection
• HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy

• At least 30 days since prior biologic therapy for the malignancy
• No concurrent cytokine support

Chemotherapy

• See Disease Characteristics
• Prior FR901228 (depsipeptide) or flavopiridol allowed provided patient did not experience dose-limiting toxicity at the dose they are scheduled to receive on study
• At least 30 days since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) for the malignancy

Endocrine therapy

• See Disease Characteristics

Radiotherapy

• See Disease Characteristics
• At least 30 days since prior radiotherapy for the malignancy
• At least 14 days since prior localized radiotherapy to non-target lesions and recovered

Surgery

• See Disease Characteristics

Other

• No more than 2 prior systemic cytotoxic treatment regimens
• No concurrent hydrochlorothiazide
• No concurrent digoxin

advanced malignant mesothelioma   recurrent malignant mesothelioma   extensive stage small cell lung cancer   recurrent non-small cell lung cancer   recurrent small cell lung cancer   stage IIIA non-small cell lung cancer   stage IIIB non-small cell lung cancer Â

stage IV non-small cell lung cancer recurrent esophageal cancer stage III esophageal cancer stage IV esophageal cancer lung metastases malignant pleural effusion

Thoracic Neoplasms Gastrointestinal Diseases Esophageal Neoplasms Pleural Effusion, Malignant Signs and Symptoms Pathologic Processes Lung Neoplasms Neoplasm Metastasis Esophageal neoplasm Non-small cell lung cancer

Digestive System Neoplasms Esophageal disorder Recurrence Carcinoma, Small Cell FR 901228 Pleural Effusion Flavopiridol Head and Neck Neoplasms Lung Diseases Gastrointestinal Neoplasms

Mesothelioma Respiratory Tract Neoplasms Neoplasms by Histologic Type Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Neoplasms, Mesothelial Growth Substances Physiological Effects of Drugs Enzyme Inhibitors Protein Kinase Inhibitors

Pharmacologic Actions Pathological Conditions, Signs and Symptoms Neoplasms Neoplastic Processes Digestive System Diseases Neoplasms by Site Respiratory Tract Diseases Therapeutic Uses Growth Inhibitors