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FR901228 and Flavopiridol in Treating Patients With Advanced Lung, Esophageal, or Pleural Cancer
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), November 2008
First Received: December 7, 2004   Last Updated: May 13, 2009   History of Changes
Sponsored by: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00098644
  Purpose

RATIONALE: Drugs used in chemotherapy, such as FR901228 and flavopiridol, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving FR901228 together with flavopiridol may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of FR901228 when given together with flavopiridol in treating patients with advanced lung, esophageal, or pleural cancer.


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

Study Type: Interventional
Study Design: Treatment
Official Title: Phase I Study Of Sequential Depsipeptide/Flavopiridol Infusion for Malignancies Involving Lungs, Esophagus, Pleura or Mediastinum

Resource links provided by NLM:


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

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

OBJECTIVES:

Primary

  • Determine the maximum tolerated dose and dose-limiting toxic effects of FR901228 (depsipeptide) when administered with flavopiridol in patients with advanced primary lung or esophageal cancer, malignant pleural mesothelioma, or lung or pleural metastases.
  • Determine the pharmacokinetics of this regimen in these patients.

Secondary

  • Analyze gene expression in laser-captured tumor cells, buccal mucosa, and peripheral blood mononuclear cells of these patients before and after treatment with this regimen.
  • Analyze mcl-1 protein expression and apoptosis in tumor biopsies from these patients before and after treatment with this regimen.

OUTLINE: This is a dose-escalation study of FR901228 (depsipeptide).

Patients receive FR901228 IV over 4 hours followed by flavopiridol IV continuously over 72 hours beginning on days 1 and 15. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of FR901228 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Six additional patients receive treatment at the MTD.

PROJECTED ACCRUAL: A total of 48 patients will be accrued for this study within 1-2 years.

  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 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00098644

Locations
United States, Maryland
NCI - Center for Cancer Research Recruiting
Bethesda, Maryland, United States, 20892
Contact: Clinical Trials Office - NCI - Center for Cancer Research     888-624-1937        
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: CDR0000398184, NCI-05-C-0010, NCI-5987
Study First Received: December 7, 2004
Last Updated: May 13, 2009
ClinicalTrials.gov Identifier: NCT00098644     History of Changes
Health Authority: Unspecified

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

Study placed in the following topic categories:
Thoracic Neoplasms
Gastrointestinal Diseases
Esophageal Neoplasms
Pleural Effusion, Malignant
Protein Kinase Inhibitors
Anti-Bacterial Agents
Respiratory Tract Diseases
Lung Neoplasms
Neoplasm Metastasis
Digestive System Neoplasms
Romidepsin
Esophageal Cancer
Recurrence
Carcinoma, Small Cell
Pleural Effusion
Flavopiridol
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:
Thoracic Neoplasms
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Gastrointestinal Diseases
Neoplasms, Mesothelial
Esophageal Neoplasms
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Protein Kinase Inhibitors
Neoplastic Processes
Neoplasms by Site
Pathologic Processes
Respiratory Tract Diseases
Lung Neoplasms
Therapeutic Uses
Neoplasm Metastasis
Growth Inhibitors
Respiratory Tract Neoplasms
Digestive System Neoplasms
Neoplasms by Histologic Type
Growth Substances
Romidepsin
Enzyme Inhibitors
Pharmacologic Actions
Flavopiridol
Neoplasms
Digestive System Diseases
Head and Neck Neoplasms
Lung Diseases
Gastrointestinal Neoplasms

ClinicalTrials.gov processed this record on July 06, 2009