A Clinical Trial to Validate Molecular Targets of Vorinostat in Patients With Stage I-III Non-Small Cell Lung Cancer
The recruitment status of this study is unknown because the information has not been verified recently.
Verified December 2011 by Dartmouth-Hitchcock Medical Center.
Recruitment status was Active, not recruiting
Information provided by (Responsible Party):
Dartmouth-Hitchcock Medical Center
First received: August 13, 2008
Last updated: December 2, 2011
Last verified: December 2011
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.
Non Small Cell Lung Cancer
||Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
||A Clinical Trial to Validate Molecular Targets of Vorinostat in Patients With Stage I-III Non-Small Cell Lung Cancer
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:
| Study Start Date:
| Estimated Primary Completion Date:
||December 2012 (Final data collection date for primary outcome measure)
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.
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- 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) ≤ 2.0 times the upper limits of normal, total bilirubin ≤ 1.5 times the upper limits of normal, serum creatinine ≤ 1.5 times the upper limit of normal or estimated creatinine clearance ≥ 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00735826
|Dartmouth-Hitchcock Medical Center
|Lebanon, New Hampshire, United States, 03756 |
Dartmouth-Hitchcock Medical Center
||Konstantin H. Dragnev, MD
||Dartmouth-Hitchcock Medical Center
No publications provided
||Dartmouth-Hitchcock Medical Center
History of Changes
|Other Study ID Numbers:
|Study First Received:
||August 13, 2008
||December 2, 2011
||United States: Institutional Review Board
Keywords provided by Dartmouth-Hitchcock Medical Center:
non-small cell lung cancer
proof of principle
resectable stage I to III NSCLC
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on December 05, 2013
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Histone Deacetylase Inhibitors
Molecular Mechanisms of Pharmacological Action