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

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ClinicalTrials.gov Identifier: NCT01935947
Recruitment Status : Terminated
First Posted : September 5, 2013
Results First Posted : July 27, 2018
Last Update Posted : July 27, 2018
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions 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
Interventions Drug: Azacitidine
Drug: Docetaxel
Drug: Entinostat
Drug: Gemcitabine Hydrochloride
Drug: Irinotecan Hydrochloride
Other: Laboratory Biomarker Analysis
Drug: Pemetrexed Disodium
Enrollment 17
Recruitment Details  
Pre-assignment Details There were seven screen failures.
Arm/Group Title Arm I (Azacitidine, Entinostat, Chemotherapy) Arm II (Azacitidine, Entinostat, Chemotherapy) Arm III (Chemotherapy)
Hide 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
Reason Not Completed
Adverse Event             0             2             0
Diease Progression             2             2             2
Death             1             0             0
Arm/Group Title Arm I (Azacitidine, Entinostat, Chemotherapy) Arm II (Azacitidine, Entinostat, Chemotherapy) Arm III (Chemotherapy) Total
Hide 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 Number of Baseline Participants 4 4 2 10
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 4 participants 2 participants 10 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
1
  25.0%
2
  50.0%
2
 100.0%
5
  50.0%
>=65 years
3
  75.0%
2
  50.0%
0
   0.0%
5
  50.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 4 participants 4 participants 2 participants 10 participants
63  (12.6) 62  (8.4) 54  (2.0) 60  (4.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 4 participants 2 participants 10 participants
Female
0
   0.0%
3
  75.0%
0
   0.0%
3
  30.0%
Male
4
 100.0%
1
  25.0%
2
 100.0%
7
  70.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 4 participants 2 participants 10 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
4
 100.0%
4
 100.0%
2
 100.0%
10
 100.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 4 participants 2 participants 10 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
1
  25.0%
1
  50.0%
2
  20.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
  25.0%
1
  25.0%
0
   0.0%
2
  20.0%
White
3
  75.0%
2
  50.0%
1
  50.0%
6
  60.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 4 participants 4 participants 2 participants 10 participants
4 4 2 10
1.Primary Outcome
Title Percentage of Patients Progression-free at 6 Months From the Time of Randomization
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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

Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
2.Secondary Outcome
Title Overall Survival (OS)
Hide Description [Not Specified]
Time Frame From the time of enrollment to trial until death, assessed up to 2 years
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
3.Secondary Outcome
Title Progression Free Survival
Hide Description From the time of randomization until radiologic or clinical progression is noted, assessed up to 2 years.
Time Frame up to 2 years
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
4.Other Pre-specified Outcome
Title Genome-wide Techniques, Including Expression Array and Methylation Array
Hide Description Expression array and methylation array will be compared to response.
Time Frame After 1 month of therapy
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
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
Hide Description [Not Specified]
Time Frame After 1 month of therapy
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
6.Other Pre-specified Outcome
Title Response to Therapy Compared to Genetic and Epigenetic Factors and Tested for Association
Hide Description [Not Specified]
Time Frame After 1 month of therapy
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
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)
Hide 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 (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/4 (25.00%)      1/4 (25.00%)      0/2 (0.00%)    
Show Serious Adverse Events Hide 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 (50.00%)      4/4 (100.00%)      1/2 (50.00%)    
Eye disorders       
Blurred Vision  1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/2 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Dysphagia  1  0/4 (0.00%)  0 1/4 (25.00%)  1 1/2 (50.00%)  1
Nervous system disorders       
Spinal Cord Depression  1  0/4 (0.00%)  0 1/4 (25.00%)  1 0/2 (0.00%)  0
Psychiatric disorders       
Confusion  1  0/4 (0.00%)  0 1/4 (25.00%)  2 0/2 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Lung Infection  1  1/4 (25.00%)  1 0/4 (0.00%)  0 0/2 (0.00%)  0
Hemoptysis  1  1/4 (25.00%)  4 1/4 (25.00%)  2 0/2 (0.00%)  0
Dyspnea  1  2/4 (50.00%)  3 2/4 (50.00%)  2 1/2 (50.00%)  2
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
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 (100.00%)      4/4 (100.00%)      2/2 (100.00%)    
Blood and lymphatic system disorders       
anemia  1  2/4 (50.00%)  4 2/4 (50.00%)  2 1/2 (50.00%)  2
General disorders       
Chest pain  1  1/4 (25.00%)  2 1/4 (25.00%)  1 1/2 (50.00%)  1
Dyspnea  1  4/4 (100.00%)  4 1/4 (25.00%)  1 1/2 (50.00%)  2
Fatigue  1  2/4 (50.00%)  4 3/4 (75.00%)  8 1/2 (50.00%)  11
Hepatobiliary disorders       
AST increased  1  1/4 (25.00%)  2 0/4 (0.00%)  0 0/2 (0.00%)  0
Skin and subcutaneous tissue disorders       
Alopecia  1  0/4 (0.00%)  0 0/4 (0.00%)  0 1/2 (50.00%)  1
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Low recruitment lead to slow accrual. Not having enough patients on the trial and high disease progression lead to closing the study.
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.
Results Point of Contact
Name/Title: Gary Rosner
Organization: Johns Hopkins University
Phone: 410-955-4884
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01935947     History of Changes
Obsolete Identifiers: NCT01846897
Other Study ID Numbers: NCI-2013-00949
NCI-2013-00949 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
NA_00081948/J1309
NA_00081948
9253 ( Other Identifier: Johns Hopkins University/Sidney Kimmel Cancer Center )
9253 ( Other Identifier: CTEP )
P30CA006973 ( U.S. NIH Grant/Contract )
First Submitted: September 3, 2013
First Posted: September 5, 2013
Results First Submitted: December 29, 2017
Results First Posted: July 27, 2018
Last Update Posted: July 27, 2018