A Clinical Trial to Validate Molecular Targets of Vorinostat in Patients With Stage I-III Non-Small Cell Lung Cancer - Non Small Cell Lung Cancer Clinical Trials

A Clinical Trial to Validate Molecular Targets of Vorinostat in Patients With Stage I-III Non-Small Cell Lung Cancer
This study is not yet open for participant recruitment.
Verified by Dartmouth-Hitchcock Medical Center, August 2008
Sponsors and Collaborators: Dartmouth-Hitchcock Medical Center
Merck

Information provided by: Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier: NCT00735826

Purpose
The primary aim is to study the effects of vorinostat on cyclin E, cyclin D1 and Ki-67 expression in lung, bronchial epithelium, and lung tumors of patients with resectable clinical stage I - III lung cancer. Secondary aims are: To evaluate the concentration of vorinostat in tumor tissue and to correlate lung tissue distribution with the plasma level in these patients; to perform exploratory analyses of the effects of vorinostat on the induction of apoptosis or necrosis in treated as compared to untreated tumors and on expression of p21, p27, EGFR and phospho-EGFR in lung tumors of patients with resectable clinical stage I - III lung cancer; to perform dynamic contrast enhanced CT of the primary tumor to study the effects of treatment on the vascular supply of the tumor and to correlate the results with the intratumoral vorinostat concentrations.

Condition Intervention
Non Small Cell Lung Cancer
Drug: Vorinostat

MedlinePlus related topics: Cancer Lung Cancer
Drug Information available for: Suberoylanilide hydroxamic acid
U.S. FDA Resources
Study Type: Interventional
Study Design: Basic Science, Open Label, Single Group Assignment, Pharmacokinetics/Dynamics Study
Official Title: A Clinical Trial to Validate Molecular Targets of Vorinostat in Patients With Stage I-III Non-Small Cell Lung Cancer

Further study details as provided by Dartmouth-Hitchcock Medical Center:

Primary Outcome Measures:
To study the effects of vorinostat on cyclin E, cyclin D1 and Ki-67 expression in lung, bronchial epithelium, and lung tumors of patients with resectable clinical stage I - III lung cancer. [ Time Frame: This will be determined once all of the data has been collected and analyzed ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
To evaluate the concentration of vorinostat in tumor tissue and to correlate lung tissue distribution with the plasma level in these patients. [ Time Frame: This will be determined once all of the data has been collected and analyzed ] [ Designated as safety issue: No ]

Perform exploratory analyses of vorinostat's effects on induction of apoptosis or necrosis in treated vs untreated tumors and on p21, p27, EGFR, and phospho-EGFR expression in lung tumors of patients with resectable clinical stage I - III lung cancer. [ Time Frame: This will be determined once all of the data has been collected and analyzed ] [ Designated as safety issue: No ]

To perform dynamic CT of the primary tumor to study the effects of treatment on the vascular supply of the tumor and to correlate the results with the intratumoral vorinostat concentrations. [ Time Frame: The CT imaging will be done prior to treatment and prior to surgery. The results will be correlated with the vorinostat concentrations once all of the data has been collected and analyzed ] [ Designated as safety issue: No ]

Estimated Enrollment: 10
Study Start Date: September 2008
Estimated Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)

Intervention Details:
Drug: Vorinostat
Vorinostat will be administered orally once daily in an open-labeled, unblinded manner to all subjects enrolled in the study. Subjects will receive vorinostat 400 mg once daily on a continuous daily basis for 7 to 10 days prior to surgical resection. Vorinostat should be taken with food within 0 to 30 minutes of a meal if possible. Patients should take the medication at approximately the same time each day on an ongoing basis. Missed doses will not be made up.
Eligibility

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

Criteria
Inclusion Criteria:

All patients must have pathological confirmation of non small cell lung cancer.
Patients must have resectable clinical stage I - III non small cell lung cancer as defined by the current International Staging System for Lung Cancer.
Age >18 years.
Adequate hepatic and renal function documented prior to study entry to include: hepatic transaminases (AST or ALT) ¡Ü 2.0 times the upper limits of normal, total bilirubin ¡Ü 1.5 times the upper limits of normal, serum creatinine ¡Ü 1.5 times the upper limit of normal or estimated creatinine clearance ¡Ý 60 mL/min.
All patients must be medical candidates for surgical resection of their non-small cell lung cancer.
All patients must give informed consent indicating they are aware of the investigational nature of this treatment.
Exclusion Criteria:

Patients may not have received radiation therapy for their non-small cell lung cancer.
Patients may not have received chemotherapy for their non-small cell lung cancer.
Women must be surgically sterilized or post-menopausal or women of childbearing potential must be using an adequate method of contraception. Women of childbearing potential must be using at least one of the following: oral, implanted, injectable contraceptive hormones, or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing abstinence or have a partner that is sterile (e.g., vasectomy). Women of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to start of study therapy.
Women who are pregnant or breast-feeding will be excluded.
Male patients with partners of childbearing potential not using an adequate method of birth control as described in the previous paragraph will be excluded.
Patients with gastrointestinal abnormalities including: inability to take oral medication, requirement for intravenous alimentation, or prior surgical procedures affecting absorption will be excluded.
A serious uncontrolled medical disorder or active infection which would impair their ability to receive study treatment will be excluded. Significant cardiac disease, including uncontrolled high blood pressure, unstable angina, congestive heart failure, myocardial infarction within the previous 3 months or serious cardiac arrythmias will be excluded. Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol will be excluded.
Patients with active HIV, HCV or HCB infection.
No prior treatment with HDAC inhibitors. Valproic acid is acceptable if not used as anticancer therapy and a 30-day wash-out period is allowed.
Exposure to other investigational agents within 30 days of study inclusion
Patients with a "currently active" second malignancy, other than nonmelanoma skin cancer and carcinoma in situ of the cervix, should not be enrolled. Patients would not be considered to have a "currently active" malignancy if they have completed therapy for a prior malignancy, are disease free from prior malignancies for >5 years or are considered by their physician to be at less than 30% risk of relapse.
Patients with history of pulmonary embolism who are not receiving anticoagulation, will be excluded.
Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00735826

Contacts
Contact: Konstantin H. Dragnev, MD (603) 650-6345 konstantin.h.dragnev@hitchcock.org
Contact: Brendan M. Slagle, BS (603) 653-0590 brendan.m.slagle@dartmouth.edu

Locations
United States, New Hampshire
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756

Sponsors and Collaborators
Dartmouth-Hitchcock Medical Center
Merck
Investigators
Principal Investigator: Konstantin H. Dragnev, MD Dartmouth-Hitchcock Medical Center

More Information

Clinical Trials at the Norris Cotton Cancer Center

Responsible Party: Dartmouth-Hitchcock Medical Center ( Konstantin H. Dragnev, MD )
Study ID Numbers: D-0828
Study First Received: August 13, 2008
Last Updated: August 14, 2008
ClinicalTrials.gov Identifier: NCT00735826 [history]
Health Authority: United States: Institutional Review Board

Keywords provided by Dartmouth-Hitchcock Medical Center:
resectable
stage I-III
NSCLC
non-small cell lung cancer
vorinostat
proof of principle
resectable stage I to III NSCLC

Study placed in the following topic categories:
Thoracic Neoplasms
Non-small cell lung cancer
Respiratory Tract Diseases
Lung Neoplasms
Lung Diseases
Vorinostat
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial
Carcinoma

Additional relevant MeSH terms:
Respiratory Tract Neoplasms
Neoplasms by Site
Neoplasms
Neoplasms by Histologic Type
Anticarcinogenic Agents
Anti-Inflammatory Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Enzyme Inhibitors
Protective Agents
Pharmacologic Actions
Analgesics, Non-Narcotic
Sensory System Agents
Therapeutic Uses
Anti-Inflammatory Agents, Non-Steroidal
Analgesics
Peripheral Nervous System Agents
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on February 10, 2009

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