Azacitidine and Entinostat Before Chemotherapy in Treating Patients With Advanced Non-small Cell Lung Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Terminated
• CT.gov ID: NCT01935947
• Collaborator: (none)
• Enrollment: 17
• Locations: 5
• Arms: 3
• Duration (Months): 47
• Patients Per Site: 3.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This randomized phase II trial studies how well azacitidine and entinostat before chemotherapy works in treating patients with non-small cell lung cancer that has spread to other places in the body. Drugs used in chemotherapy, such as azacitidine, irinotecan hydrochloride, gemcitabine hydrochloride, docetaxel, and pemetrexed disodium, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Entinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving azacitidine and entinostat before chemotherapy may work better in treating patients with non-small cell lung cancer.

Condition or Disease	Intervention/Treatment	Phase
Recurrent Non-Small Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer	Drug: Azacitidine; Drug: Azacitidine; Drug: Docetaxel; Drug: Entinostat; Drug: Gemcitabine Hydrochloride; Drug: Irinotecan Hydrochloride; Other: Laboratory Biomarker Analysis; Drug: Pemetrexed Disodium	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. Percentage of patients progression-free at 6 months from time of randomization.

SECONDARY OBJECTIVES:

1. Progression-free survival (PFS). II. Overall survival (OS).

OUTLINE: Patients are randomized to 1 of 3 treatment arms.

ARM A: 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 for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or progressive disease receive chemotherapy of the treating oncologist's choice comprising irinotecan hydrochloride intravenously (IV) on day 1, docetaxel IV on day 1, pemetrexed disodium IV on day 1, or gemcitabine hydrochloride IV on days 1 and 8. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive azacitidine PO on days 1-21 and entinostat PO on days 3 and 10. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or progressive disease receive chemotherapy of the treating oncologist's choice as in Arm A.

ARM C: Patients receive chemotherapy of the treating oncologist's choice as in Arm A.

After completion of treatment, patients are followed up every 3-6 months for 24 months and then yearly thereafter.

Study Design

• Study Type: Interventional
• Actual Enrollment: 17 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Phase II Trial of Cytotoxic Chemotherapy With or Without Epigenetic Priming in Patients With Advanced Non-Small Cell Lung Cancer
• Study Start Date: May 1, 2013
• Actual Primary Completion Date: Apr 1, 2017
• Actual Study Completion Date: Apr 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I (azacitidine, entinostat, chemotherapy) Patients receive azacitidine SC on days 1-6 and 8-10 and entinostat PO on days 3 and 10. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or progressive disease receive chemotherapy of the treating oncologist's choice comprising irinotecan hydrochloride IV on day 1, docetaxel IV on day 1, pemetrexed disodium IV on day 1, or gemcitabine hydrochloride IV on days 1 and 8. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.	Drug: Azacitidine; Given SC; Other Names: 5 AZC 5-AC 5-Azacytidine 5-AZC Azacytidine Azacytidine, 5- Ladakamycin Mylosar U-18496 Vidaza ; Drug: Docetaxel; Given IV; Other Names: Docecad RP56976 Taxotere Taxotere Injection Concentrate ; Drug: Entinostat; Given PO; Other Names: HDAC inhibitor SNDX-275 MS 27-275 MS-275 SNDX-275 ; Drug: Gemcitabine Hydrochloride; Given IV; Other Names: dFdCyd Difluorodeoxycytidine Hydrochloride Gemzar LY-188011 LY188011 ; Drug: Irinotecan Hydrochloride; Given IV; Other Names: Campto Camptosar Camptothecin 11 Camptothecin-11 CPT 11 CPT-11 Irinomedac U-101440E ; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Pemetrexed Disodium; Given IV; Other Names: Alimta LY231514 N-[4-[2-(2-Amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic Acid Disodium Salt
Experimental: Arm II (azacitidine, entinostat, chemotherapy) Patients receive azacitidine PO on days 1-21 and entinostat PO on days 3 and 10. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or progressive disease receive chemotherapy of the treating oncologist's choice as in Arm A.	Drug: Azacitidine; Given PO; Other Names: 5 AZC 5-AC 5-Azacytidine 5-AZC Azacytidine Azacytidine, 5- Ladakamycin Mylosar U-18496 Vidaza ; Drug: Docetaxel; Given IV; Other Names: Docecad RP56976 Taxotere Taxotere Injection Concentrate ; Drug: Entinostat; Given PO; Other Names: HDAC inhibitor SNDX-275 MS 27-275 MS-275 SNDX-275 ; Drug: Gemcitabine Hydrochloride; Given IV; Other Names: dFdCyd Difluorodeoxycytidine Hydrochloride Gemzar LY-188011 LY188011 ; Drug: Irinotecan Hydrochloride; Given IV; Other Names: Campto Camptosar Camptothecin 11 Camptothecin-11 CPT 11 CPT-11 Irinomedac U-101440E ; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Pemetrexed Disodium; Given IV; Other Names: Alimta LY231514 N-[4-[2-(2-Amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic Acid Disodium Salt
Active Comparator: Arm III (chemotherapy) Patients receive chemotherapy of the treating oncologist's choice as in Arm A.	Drug: Docetaxel; Given IV; Other Names: Docecad RP56976 Taxotere Taxotere Injection Concentrate ; Drug: Gemcitabine Hydrochloride; Given IV; Other Names: dFdCyd Difluorodeoxycytidine Hydrochloride Gemzar LY-188011 LY188011 ; Drug: Irinotecan Hydrochloride; Given IV; Other Names: Campto Camptosar Camptothecin 11 Camptothecin-11 CPT 11 CPT-11 Irinomedac U-101440E ; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Pemetrexed Disodium; Given IV; Other Names: Alimta LY231514 N-[4-[2-(2-Amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic Acid Disodium Salt

Outcome Measures

Primary Outcome Measures

1. Percentage of Patients Progression-free at 6 Months From the Time of Randomization [At 6 months]

   The final analysis will be by Fisher's Exact test, with percentage of patients who have not progressed as the outcome variable. Using Fisher's Exact test for analysis with 55 patients per treatment group will provide 88% power to detect an increase from 40% (chemotherapy alone) to 65% (epigenetic therapy followed by chemotherapy) in the number of patients who are progression free at six months.

Secondary Outcome Measures

1. Overall Survival (OS) [From the time of enrollment to trial until death, assessed up to 2 years]

2. Progression Free Survival [up to 2 years]

   From the time of randomization until radiologic or clinical progression is noted, assessed up to 2 years.

Other Outcome Measures

1. Genome-wide Techniques, Including Expression Array and Methylation Array [After 1 month of therapy]

   Expression array and methylation array will be compared to response.

2. Predictive and Prognostic Value of the Previously Defined Epigenetic Signature, Comprised of Promoter Methylation Analysis of 4 Target Genes [After 1 month of therapy]

3. Response to Therapy Compared to Genetic and Epigenetic Factors and Tested for Association [After 1 month of therapy]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients must have histologically or cytologically proven non-small cell lung cancer; tumor tissue must be available from all patients prior to initiation of protocol therapy, either from original diagnostic biopsy, or biopsy performed prior to initiation of protocol therapy

• 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 for non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam

• Patients must have received 1 prior platinum containing doublet regardless of mutation status

• Patients with targetable mutation i.e. epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK), must have been treated with at least 1 prior tyrosine kinase inhibitor (TKI)

• Prior immunotherapy is allowed

• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (Karnofsky >= 70%)

• Life expectancy of greater than 12 weeks

• Leukocytes >= 3,000/mcL

• Absolute neutrophil count >= 1,500/mcL

• Platelets >= 100,000/mcL

• Total bilirubin within normal institutional limits

• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transferase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transferase [SGPT]) =< 2.5 X institutional upper limit of normal

• Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^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 she or her partner is participating in this study, she should inform her treating physician immediately

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

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 who are 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 may be treated with steroids as clinically indicated

• 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, azacitidine, mannitol, irinotecan, docetaxel, pemetrexed, or gemcitabine, or other agents used in the study

• Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, New York Heart Association (NYHA) class 3-4 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	USC / Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
2	USC Norris Oncology/Hematology-Newport Beach	Newport Beach	California	United States	92663
3	Johns Hopkins Bayview Medical Center	Baltimore	Maryland	United States	21224
4	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland	United States	21287
5	Medical University of South Carolina	Charleston	South Carolina	United States	29425

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Julie Brahmer, Johns Hopkins University/Sidney Kimmel Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 11, 2016

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT01935947
• Other Study ID Numbers: NCI-2013-00949; NCI-2013-00949; NA_00081948/J1309; NA_00081948; 9253; 9253; P30CA006973; NCT01846897
• First Posted: Sep 5, 2013
• Last Update Posted: Jul 27, 2018
• Last Verified: Jun 1, 2018

• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Gemcitabine; Azacitidine; Docetaxel; Irinotecan; Pemetrexed; Camptothecin; Entinostat; Histone Deacetylase Inhibitors

Study Results

Participant Flow

Pre-assignment Detail	There were seven screen failures.

Arm/Group Title	Arm I (Azacitidine, Entinostat, Chemotherapy)	Arm II (Azacitidine, Entinostat, Chemotherapy)	Arm III (Chemotherapy)
Arm/Group Description	Patients receive azacitidine SC on days 1-6 and 8-10 and entinostat PO on days 3 and 10. Treatment repeats every 28 days for 2 courses, then chemotherapy. Treatment repeats every 21 days.	Patients receive azacitidine PO on days 1-21 and entinostat PO on days 3 and 10. Treatment repeats every 28 days for 2 courses. Patients receive chemotherapy of the treating oncologist's choice as in Arm A.	Patients receive chemotherapy of the treating oncologist's choice as in Arm A.
Period Title: Overall Study
STARTED	4	4	2
Epigenetic Therapy	4	4	0
Cytotoxic Therapy	3	3	2
COMPLETED	1	0	0
NOT COMPLETED	3	4	2

Baseline Characteristics

Arm/Group Title	Arm I (Azacitidine, Entinostat, Chemotherapy)	Arm II (Azacitidine, Entinostat, Chemotherapy)	Arm III (Chemotherapy)	Total
Arm/Group Description	Patients receive azacitidine SC on days 1-6 and 8-10 and entinostat PO on days 3 and 10. Treatment repeats every 28 days for 2 courses then patients receive chemotherapy. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.	Patients receive azacitidine PO on days 1-21 and entinostat PO on days 3 and 10. Treatment repeats every 28 days for 2 courses, and then patients receive chemotherapy as in Arm A.	Patients receive chemotherapy of the treating oncologist's choice as in Arm A.	Total of all reporting groups
Overall Participants	4	4	2	10
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	1 25%	2 50%	2 100%	5 50%
>=65 years	3 75%	2 50%	0 0%	5 50%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63 (12.6)	62 (8.4)	54 (2.0)	60 (4.0)
Sex: Female, Male (Count of Participants)
Female	0 0%	3 75%	0 0%	3 30%
Male	4 100%	1 25%	2 100%	7 70%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	4 100%	4 100%	2 100%	10 100%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	1 25%	1 50%	2 20%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	1 25%	1 25%	0 0%	2 20%
White	3 75%	2 50%	1 50%	6 60%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	4 100%	4 100%	2 100%	10 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Patients Progression-free at 6 Months From the Time of Randomization
Description	The final analysis will be by Fisher's Exact test, with percentage of patients who have not progressed as the outcome variable. Using Fisher's Exact test for analysis with 55 patients per treatment group will provide 88% power to detect an increase from 40% (chemotherapy alone) to 65% (epigenetic therapy followed by chemotherapy) in the number of patients who are progression free at six months.
Time Frame	At 6 months

Outcome Measure Data

Analysis Population Description

Data was not collected to assess this outcome measure due to early study termination.

Arm/Group Title	Arm I (Azacitidine, Entinostat, Chemotherapy)	Arm II (Azacitidine, Entinostat, Chemotherapy)	Arm III (Chemotherapy)
Arm/Group Description	Patients receive azacitidine SC on days 1-6 and 8-10 and entinostat PO on days 3 and 10. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or progressive disease receive chemotherapy of the treating oncologist's choice comprising irinotecan hydrochloride IV on day 1, docetaxel IV on day 1, pemetrexed disodium IV on day 1, or gemcitabine hydrochloride IV on days 1 and 8. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Azacitidine: Given SC Docetaxel: Given IV Entinostat: Given PO Gemcitabine Hydrochloride: Given IV Irinotecan Hydrochloride: Given IV Laboratory Biomarker Analysis: Correlative studies Pemetrexed Disodium: Given IV	Patients receive azacitidine PO on days 1-21 and entinostat PO on days 3 and 10. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or progressive disease receive chemotherapy of the treating oncologist's choice as in Arm A. Azacitidine: Given PO Docetaxel: Given IV Entinostat: Given PO Gemcitabine Hydrochloride: Given IV Irinotecan Hydrochloride: Given IV Laboratory Biomarker Analysis: Correlative studies Pemetrexed Disodium: Given IV	Patients receive chemotherapy of the treating oncologist's choice as in Arm A. Docetaxel: Given IV Gemcitabine Hydrochloride: Given IV Irinotecan Hydrochloride: Given IV Laboratory Biomarker Analysis: Correlative studies Pemetrexed Disodium: Given IV
Measure Participants	0	0	0

2. Secondary Outcome

Title	Overall Survival (OS)
Time Frame	From the time of enrollment to trial until death, assessed up to 2 years

Outcome Measure Data

Analysis Population Description

Data was not collected to assess this outcome measure due to early study termination.

Arm/Group Title	Arm I (Azacitidine, Entinostat, Chemotherapy)	Arm II (Azacitidine, Entinostat, Chemotherapy)	Arm III (Chemotherapy)
Arm/Group Description	Patients receive azacitidine SC on days 1-6 and 8-10 and entinostat PO on days 3 and 10. Treatment repeats every 28 days for 2 courses, then chemotherapy. Treatment repeats every 21 days.	Patients receive azacitidine PO on days 1-21 and entinostat PO on days 3 and 10. Treatment repeats every 28 days for 2 courses. Patients receive chemotherapy of the treating oncologist's choice as in Arm A.	Patients receive chemotherapy of the treating oncologist's choice as in Arm A.
Measure Participants	0	0	0

3. Secondary Outcome

Title	Progression Free Survival
Description	From the time of randomization until radiologic or clinical progression is noted, assessed up to 2 years.
Time Frame	up to 2 years

Outcome Measure Data

Analysis Population Description

Data was not collected to assess this outcome measure due to early study termination.

Arm/Group Title	Arm I (Azacitidine, Entinostat, Chemotherapy)	Arm II (Azacitidine, Entinostat, Chemotherapy)	Arm III (Chemotherapy)
Arm/Group Description	Patients receive azacitidine SC on days 1-6 and 8-10 and entinostat PO on days 3 and 10. Treatment repeats every 28 days for 2 courses, then chemotherapy. Treatment repeats every 21 days.	Patients receive azacitidine PO on days 1-21 and entinostat PO on days 3 and 10. Treatment repeats every 28 days for 2 courses. Patients receive chemotherapy of the treating oncologist's choice as in Arm A.	Patients receive chemotherapy of the treating oncologist's choice as in Arm A.
Measure Participants	0	0	0

4. Other Pre-specified Outcome

Title	Genome-wide Techniques, Including Expression Array and Methylation Array
Description	Expression array and methylation array will be compared to response.
Time Frame	After 1 month of therapy

Outcome Measure Data

Analysis Population Description

Data was not collected to assess this outcome measure due to early study termination.

Arm/Group Title	Arm I (Azacitidine, Entinostat, Chemotherapy)	Arm II (Azacitidine, Entinostat, Chemotherapy)	Arm III (Chemotherapy)
Arm/Group Description	Patients receive azacitidine SC on days 1-6 and 8-10 and entinostat PO on days 3 and 10. Treatment repeats every 28 days for 2 courses, then chemotherapy. Treatment repeats every 21 days.	Patients receive azacitidine PO on days 1-21 and entinostat PO on days 3 and 10. Treatment repeats every 28 days for 2 courses. Patients receive chemotherapy of the treating oncologist's choice as in Arm A.	Patients receive chemotherapy of the treating oncologist's choice as in Arm A.
Measure Participants	0	0	0

5. Other Pre-specified Outcome

Title	Predictive and Prognostic Value of the Previously Defined Epigenetic Signature, Comprised of Promoter Methylation Analysis of 4 Target Genes
Time Frame	After 1 month of therapy

Outcome Measure Data

Analysis Population Description

Data was not collected to assess this outcome measure due to early study termination.

Arm/Group Title	Arm I (Azacitidine, Entinostat, Chemotherapy)	Arm II (Azacitidine, Entinostat, Chemotherapy)	Arm III (Chemotherapy)
Arm/Group Description	Patients receive azacitidine SC on days 1-6 and 8-10 and entinostat PO on days 3 and 10. Treatment repeats every 28 days for 2 courses, then chemotherapy. Treatment repeats every 21 days.	Patients receive azacitidine PO on days 1-21 and entinostat PO on days 3 and 10. Treatment repeats every 28 days for 2 courses. Patients receive chemotherapy of the treating oncologist's choice as in Arm A.	Patients receive chemotherapy of the treating oncologist's choice as in Arm A.
Measure Participants	0	0	0

6. Other Pre-specified Outcome

Title	Response to Therapy Compared to Genetic and Epigenetic Factors and Tested for Association
Time Frame	After 1 month of therapy

Outcome Measure Data

Analysis Population Description

Data was not collected to assess this outcome measure due to early study termination.

Arm/Group Title	Arm I (Azacitidine, Entinostat, Chemotherapy)	Arm II (Azacitidine, Entinostat, Chemotherapy)	Arm III (Chemotherapy)
Arm/Group Description	Patients receive azacitidine SC on days 1-6 and 8-10 and entinostat PO on days 3 and 10. Treatment repeats every 28 days for 2 courses, then chemotherapy. Treatment repeats every 21 days.	Patients receive azacitidine PO on days 1-21 and entinostat PO on days 3 and 10. Treatment repeats every 28 days for 2 courses. Patients receive chemotherapy of the treating oncologist's choice as in Arm A.	Patients receive chemotherapy of the treating oncologist's choice as in Arm A.
Measure Participants	0	0	0

Adverse Events

Time Frame	up to 2 years
Adverse Event Reporting Description	Adverse events and serious adverse events will be collected for up to 30 days after the last administration of the investigational agent/intervention
Arm/Group Title	Arm I (Azacitidine, Entinostat, Chemotherapy)		Arm II (Azacitidine, Entinostat, Chemotherapy)		Arm III (Chemotherapy)
Arm/Group Description	Patients receive azacitidine SC on days 1-6 and 8-10 and entinostat PO on days 3 and 10. Treatment repeats every 28 days for 2 course, and then receive chemotherapy. Treatment repeats every 21 days.		Patients receive azacitidine PO on days 1-21 and entinostat PO on days 3 and 10. Treatment repeats every 28 days for 2 courses, and then receive chemotherapy as in Arm A.		Patients receive chemotherapy as in Arm A.
All Cause Mortality
	Arm I (Azacitidine, Entinostat, Chemotherapy)		Arm II (Azacitidine, Entinostat, Chemotherapy)		Arm III (Chemotherapy)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/4 (25%)		1/4 (25%)		0/2 (0%)
Serious Adverse Events
	Arm I (Azacitidine, Entinostat, Chemotherapy)		Arm II (Azacitidine, Entinostat, Chemotherapy)		Arm III (Chemotherapy)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/4 (50%)		4/4 (100%)		1/2 (50%)
Eye disorders
Blurred Vision	1/4 (25%)	1	0/4 (0%)	0	0/2 (0%)	0
Musculoskeletal and connective tissue disorders
Dysphagia	0/4 (0%)	0	1/4 (25%)	1	1/2 (50%)	1
Nervous system disorders
Spinal Cord Depression	0/4 (0%)	0	1/4 (25%)	1	0/2 (0%)	0
Psychiatric disorders
Confusion	0/4 (0%)	0	1/4 (25%)	2	0/2 (0%)	0
Respiratory, thoracic and mediastinal disorders
Lung Infection	1/4 (25%)	1	0/4 (0%)	0	0/2 (0%)	0
Hemoptysis	1/4 (25%)	4	1/4 (25%)	2	0/2 (0%)	0
Dyspnea	2/4 (50%)	3	2/4 (50%)	2	1/2 (50%)	2
Other (Not Including Serious) Adverse Events
	Arm I (Azacitidine, Entinostat, Chemotherapy)		Arm II (Azacitidine, Entinostat, Chemotherapy)		Arm III (Chemotherapy)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/4 (100%)		4/4 (100%)		2/2 (100%)
Blood and lymphatic system disorders
anemia	2/4 (50%)	4	2/4 (50%)	2	1/2 (50%)	2
General disorders
Chest pain	1/4 (25%)	2	1/4 (25%)	1	1/2 (50%)	1
Dyspnea	4/4 (100%)	4	1/4 (25%)	1	1/2 (50%)	2
Fatigue	2/4 (50%)	4	3/4 (75%)	8	1/2 (50%)	11
Hepatobiliary disorders
AST increased	1/4 (25%)	2	0/4 (0%)	0	0/2 (0%)	0
Skin and subcutaneous tissue disorders
Alopecia	0/4 (0%)	0	0/4 (0%)	0	1/2 (50%)	1

Limitations/Caveats

Low recruitment lead to slow accrual. Not having enough patients on the trial and high disease progression lead to closing the study.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.