A Clinical Trial to Validate Molecular Targets of Vorinostat in Patients With Stage I-III Non-Small Cell Lung Cancer
Information source: Dartmouth-Hitchcock Medical Center
Information obtained from ClinicalTrials.gov on October 19, 2009
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Non Small Cell Lung Cancer
Intervention: Vorinostat (Drug)
Phase: N/A
Status: Recruiting
Sponsored by: Dartmouth-Hitchcock Medical Center Official(s) and/or principal investigator(s):
Konstantin H. Dragnev, MD, Principal Investigator, Affiliation: Dartmouth-Hitchcock Medical Center
Overall contact:
Konstantin H. Dragnev, MD, Phone: (603) 650-6345, Email: konstantin.h.dragnev@hitchcock.org
Summary
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.
Clinical Details
Official title: A Clinical Trial to Validate Molecular Targets of Vorinostat in Patients With Stage I-III Non-Small Cell Lung Cancer
Study design: Basic Science, Open Label, Single Group Assignment, Pharmacokinetics/Dynamics Study
Primary outcome: 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 outcome: To evaluate the concentration of vorinostat in tumor tissue and to correlate lung tissue distribution with the plasma level in these patients.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. 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.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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) ≤ 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.
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.
Locations and Contacts
Konstantin H. Dragnev, MD, Phone: (603) 650-6345, Email: konstantin.h.dragnev@hitchcock.org
Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire 03756, United States; Recruiting
Brendan M. Slagle, BS, Phone: (603) 653-0590, Email: brendan.m.slagle@hitchcock.org
Heidi E. McAllister, Phone: (603) 650-5475, Email: heidi.e.mcallister@hitchcock.org
Konstantin H Dragnev, MD, Principal Investigator
James R Rigas, MD, Sub-Investigator
David W. Johnstone, MD, Sub-Investigator
Wendye M. DiSalvo, MSN, ARNP, AOCN, Sub-Investigator
Additional Information
Clinical Trials at the Norris Cotton Cancer Center
Starting date: March 2009
Last updated: March 27, 2009
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