Azacitidine and Entinostat in Treating Patients With Recurrent Advanced Non-Small Cell Lung Cancer



Status:Recruiting
Conditions:Lung Cancer, Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:18 - Any
Updated:5/5/2014
Start Date:August 2006

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A Phase I/II Study of Entinostat in Combination With 5-Azacytidine in Patients With Recurrent Advanced Non-Small Cell Lung Cancer

This phase I/II trial is studying the side effects and best dose of azacitidine when given
together with entinostat and to see how well they work in treating patients with recurrent
advanced non-small cell lung cancer. Azacitidine and entinostat may stop the growth of tumor
cells by blocking some of the enzymes needed for cell growth. Giving azacitidine together
with entinostat may kill more tumor cells.

PRIMARY OBJECTIVES:

I. To assess safety, characterize toxicities, and determine the maximum tolerated dose of
5-AZA (azacitidine) with a fixed-dose of entinostat in patients with recurrent advanced
non-small cell lung cancer (NSCLC). (Phase I) II. To determine the objective response rate
of 5-AZA and entinostat in patients with recurrent NSCLC. (Phase II)

SECONDARY OBJECTIVES:

I. To determine the pharmacokinetic profile of 5-AZA and entinostat in patients with
recurrent NSCLC.

II. To assess the pharmacodynamic effects of 5-AZA and entinostat on deoxyribonucleic acid
(DNA) methylation, histone acetylation, and gene re-expression in patients with recurrent
NSCLC through analysis of blood, sputum and tissue biopsies.

III. To explore the effect of 5-AZA and entinostat on progression-free and overall survival
in patients with recurrent advanced non-small cell lung cancer.

IV. To explore the differing response rates and progression-free survivals of two schedules
of 5-AZA and entinostat in patients with recurrent advanced non-small cell lung cancer.

OUTLINE: This is a multicenter, phase I, dose-escalation study of azacitidine followed by an
open-label, phase II study.

Patients receive azacitidine subcutaneously (SC) on days 1-6 and 8-10 and entinostat orally
(PO) on days 3 and 10. Treatment repeats every 28 days in the absence of disease progression
or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months.

Inclusion Criteria:

- Patients must have histologically or cytologically confirmed metastatic or
unresectable NSCLC

- Patient must have failed at least one previous chemotherapy regimen

- Patients must have measurable disease, defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded) as >=
20 mm with conventional techniques or as >= 10 mm with spiral computed tomography
(CT) scan

- Life expectancy of greater than 12 weeks

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) =< 2 (Karnofsky >=
60%)

- Leukocytes >= 3,000/mcL

- Absolute neutrophil count >= 1,500/mcL

- Platelet count >= 100,000/mcL

- Total bilirubin within normal institutional limits

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT] and
alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2.5 x
upper limit of normal

- Creatinine within normal institutional limits OR creatinine clearance >= 60
mL/min/1.73m^2 for patients with creatinine levels above institutional normal

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry and
for the duration of study participation; should a woman become pregnant or suspect
she is pregnant while participating in this study, she should inform her treating
physician immediately

- Ability to understand and the willingness to sign a written informed consent document

- Patients who have a major objective response to treatment on this protocol, and who
experience progression of disease at least 1 year after completion of protocol
consent and therapy, may be re-treated at the previously effective dose and schedule

Exclusion Criteria:

- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or those who have not
recovered from adverse events due to agents administered more than 4 weeks earlier

- Patients may not be receiving any other investigational agents

- Patients with uncontrolled brain metastases; patients with brain metastases must have
stable neurologic status following local therapy (surgery or radiation) for at least
4 weeks, and must be without neurologic dysfunction that would confound the
evaluation of neurologic and other adverse events

- Patients with liver metastases that replace greater than 30% of the liver parenchyma

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to entinostat, 5-AZA, mannitol or other agents used in the study

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- Pregnant women are excluded from this study; breastfeeding should be discontinued if
the mother is treated on this protocol

- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
therapy are ineligible
We found this trial at
5
sites
San Diego, California 92121
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4940 Eastern Ave
Baltimore, Maryland 21224
(410) 550-0100
Johns Hopkins Bayview Medical Center There is no better story in American medicine in the...
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401 North Broadway
Baltimore, Maryland 21287
410-955-5000
Johns Hopkins University-Sidney Kimmel Cancer Center The name Johns Hopkins has become synonymous with excellence...
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1441 Eastlake Ave
Los Angeles, California 90033
(323) 865-3000
U.S.C./Norris Comprehensive Cancer Center The USC Norris Comprehensive Cancer Center, located in Los Angeles, is...
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Los Angeles, CA
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