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Decitabine and FR901228 in Treating Patients With Advanced Lung Cancer, Esophageal Cancer, Pleural Mesothelioma, or Lung Metastases
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), November 2008
First Received: July 8, 2002   Last Updated: January 28, 2009   History of Changes
Sponsored by: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00041158
  Purpose

RATIONALE: Drugs used in chemotherapy, such as decitabine and FR901228, use different ways to stop tumor cells from dividing so they stop growing or die.

Using more than one drug may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of decitabine and FR901228 in treating patients with unresectable advanced lung cancer, esophageal cancer, pleural mesothelioma, or lung metastases.


Condition Intervention Phase
Esophageal Cancer
Lung Cancer
Malignant Mesothelioma
Metastatic Cancer
Drug: celecoxib
Drug: decitabine
Drug: romidepsin
Phase I

MedlinePlus related topics: Cancer Esophageal Cancer Esophagus Disorders Lung Cancer Mesothelioma
Drug Information available for: FR 901228 Celecoxib 5-Aza-2'-deoxycytidine
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment
Official Title: Phase I Study of Gene Induction Mediated by Sequential Decitabine/Depsipeptide Infusion in Subjects With Pulmonary and Pleural Malignancies

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

Estimated Enrollment: 40
Study Start Date: May 2002
Estimated Primary Completion Date: July 2003 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • Determine the pharmacokinetics, toxicity, and maximum tolerated dose of decitabine and FR901228 (depsipeptide) in patients with unresectable pulmonary, esophageal, or pleural malignancies.
  • Determine serologic response to NY-ESO-1 in these patients before and after receiving this regimen.
  • Evaluate apoptosis in tumor biopsies of these patients before and after receiving this regimen.

OUTLINE: This is a dose-escalation study.

Patients receive decitabine IV continuously on days 1-3 and FR901228 (depsipeptide) IV over 4 hours on days 4 and 10. Courses repeat every 33-36 days in the absence of disease progression or unacceptable toxicity.

Sequential dose escalation of decitabine is followed by sequential dose escalation of FR901228. Cohorts of 3-6 patients receive escalating doses of decitabine and then FR901228 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

Once the MTD is determined, two additional cohorts (6 lung cancer and 6 mesothelioma patients) receive decitabine and FR901228 as above at the MTD. These patients also receive oral celecoxib twice daily on days 4-34 of each course.

PROJECTED ACCRUAL: A maximum of 40 patients will be accrued for this study within 10.8-13.5 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed primary small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), advanced esophageal cancer, or pleural mesothelioma

    • Cancers of non-thoracic origin with metastases to the lungs or pleura eligible
    • Unresectable disease
  • Primary or metastatic disease must be accessible for biopsy by endoscopic or percutaneous fine-needle aspiration techniques
  • No limited stage SCLC or operable NSCLC
  • No active intracranial or leptomeningeal metastases

    • Patients with prior intracranial metastases that have been treated with prior surgery or radiotherapy are eligible provided there is no evidence of active disease and no requirement for anticonvulsant therapy or steroids after treatment

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Performance status:

  • ECOG 0-2

Life expectancy:

  • At least 3 months

Hematopoietic:

  • Absolute neutrophil count at least 1,500/mm^3 (without cytokine support)
  • Platelet count greater than 100,000/mm^3 (without transfusion)

Hepatic:

  • Bilirubin less than 1.5 times upper limit of normal
  • PT normal

Renal:

  • Creatinine no greater than 1.6 mg/dL OR
  • Creatinine clearance greater than 70 mL/min

Cardiovascular:

  • LVEF less than 50% by MUGA scan or echocardiogram
  • No New York Heart Association class III or IV heart disease (i.e., decompensated heart failure)
  • No myocardial infarction within the past year
  • No uncontrolled arrhythmias
  • No prior serious ventricular arrhythmias not controlled by coronary artery bypass surgery
  • No prosthetic heart valves requiring anticoagulation
  • No deep venous thrombosis
  • No left ventricular hypertrophy
  • No history of sustained ventricular tachycardia, ventricular fibrillation, Torsades de Pointes, or cardiac arrest without currently having an automatic implantable cardioverter defibrillator in place
  • No congenital long QT syndrome or QTc > 480 msec
  • No Mobitz II second degree block without currently having a pacemaker in place
  • No cardiac arrhythmias requiring antiarrhytmic medication except a beta blocker or calcium channel blocker
  • No hypertrophic or restrictive cardiomyopathy from prior treatment of other causes
  • No uncontrolled hypertension (i.e., blood pressure ≥160/95)
  • No clinically significant active myocardial ischemia on the basis of nuclear imaging or angiography
  • No history of coronary artery disease (e.g., angina Canadian Class II-IV or positive stress imaging study)
  • No evidence of cardiac ischemia (e.g., ST depression greater than or equal to 2 mm) by EKG
  • First degree or Mobitz second degree block, bradyarrhythmias, or sick sinus syndrome allowed provided patient undergo Holter monitoring and cardiac evaluation

Pulmonary:

  • FEV_1 and DLCO greater than 30% predicted
  • Partial pressure of carbon dioxide (pCO_2) less than 50 mm Hg on room air
  • Partial pressure of oxygen (pO_2) greater than 60 mm Hg on room air
  • No pulmonary embolism

Other:

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

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • At least 30 days since prior anticancer biologic therapy

Chemotherapy:

  • At least 30 days since prior anticancer chemotherapy
  • Prior decitabine or FR901228 (depsipeptide) allowed provided no dose-limiting toxicity was experienced at the scheduled dose

Endocrine therapy:

  • See Disease Characteristics

Radiotherapy:

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

Surgery:

  • See Disease Characteristics

Other:

  • No more than 2 prior systemic cytotoxic treatment regimens
  • At least a 5 half-life washout period since and no concurrent medication causing corrected QT interval (QTc) prolongation
  • No concurrent medication causing corrected QTc prolongation
  • No concurrent anticonvulsants
  • No concurrent hydrochlorothiazide diuretics
  • No concurrent digitalis
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00041158

Locations
United States, Maryland
NCI - Center for Cancer Research Recruiting
Bethesda, Maryland, United States, 20892
Contact: Tricia Kunst, RN     301-451-1233     tricia_kunst@nih.gov    
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office Recruiting
Bethesda, Maryland, United States, 20892-1182
Contact: Clinical Trials Office - Warren Grant Magnusen Clinical Center     888-NCI-1937        
Sponsors and Collaborators
Investigators
Study Chair: David S. Schrump, MD NCI - Surgery Branch
  More Information

Additional Information:
No publications provided

Study ID Numbers: CDR0000069448, NCI-02-C-0205, NCI-5270
Study First Received: July 8, 2002
Last Updated: January 28, 2009
ClinicalTrials.gov Identifier: NCT00041158     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
recurrent non-small cell lung cancer
extensive stage small cell lung cancer
recurrent small cell lung cancer
advanced malignant mesothelioma
recurrent malignant mesothelioma
stage IIIA non-small cell lung cancer
stage IIIB non-small cell lung cancer
stage IV non-small cell lung cancer
lung metastases
malignant pleural effusion
stage IV esophageal cancer
recurrent esophageal cancer

Study placed in the following topic categories:
Antimetabolites
Thoracic Neoplasms
Gastrointestinal Diseases
Esophageal Neoplasms
Pleural Effusion, Malignant
Anti-Bacterial Agents
Respiratory Tract Diseases
Lung Neoplasms
Neoplasm Metastasis
Digestive System Neoplasms
Celecoxib
Romidepsin
Esophageal Cancer
Decitabine
Recurrence
Carcinoma, Small Cell
Pleural Effusion
Digestive System Diseases
Esophageal Disorder
Head and Neck Neoplasms
Lung Diseases
Gastrointestinal Neoplasms
Mesothelioma
Non-small Cell Lung Cancer
Esophageal Diseases
Carcinoma, Non-Small-Cell Lung
Adenoma
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:
Antimetabolites
Thoracic Neoplasms
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Gastrointestinal Diseases
Neoplasms, Mesothelial
Esophageal Neoplasms
Antibiotics, Antineoplastic
Neoplastic Processes
Neoplasms by Site
Pathologic Processes
Respiratory Tract Diseases
Lung Neoplasms
Therapeutic Uses
Neoplasm Metastasis
Respiratory Tract Neoplasms
Digestive System Neoplasms
Neoplasms by Histologic Type
Romidepsin
Enzyme Inhibitors
Decitabine
Pharmacologic Actions
Neoplasms
Digestive System Diseases
Head and Neck Neoplasms
Lung Diseases
Gastrointestinal Neoplasms
Mesothelioma
Esophageal Diseases

ClinicalTrials.gov processed this record on May 07, 2009