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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2012-02901 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| NA_00038631 | |||
| J1037 | Other Identifier | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital | |
| 8311 | Other Identifier | CTEP | |
| P30CA006973 | U.S. NIH Grant/Contract | View source |
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Slow Accrual due to patients not wanting daily clinic administration of 5AZA and/or 6 months of treatment after surgery.
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This study combines the deoxyribonucleic acid (DNA) methyltransferase inhibitor, 5-azacitidine (5-AZA), with an orally bioavailable histone deacetylase inhibitor, entinostat (SNDX-275), for the adjuvant treatment of patients with resected stage I non-small cell lung cancer (NCSLC).
PRIMARY OBJECTIVES:
I. To assess the effect of 5-azacitidine and entinostat on the hazard of 3 year progression-free survival in patients with resected stage I non-small cell lung cancer.
SECONDARY OBJECTIVES:
I. To assess the safety, tolerability and toxicity of entinostat and 5-azacitidine in patients with resected stage I non-small cell lung cancer.
II. To explore the effect of entinostat and 5-azacitidine on median disease-free and overall survival in patients with resected stage I non-small cell lung cancer.
III. To assess the pharmacodynamic effects of 5-azacitidine and entinostat on DNA methylation and gene re-expression in patients with resected stage I NSCLC through analysis of sputum.
IV. To estimate the effect of entinostat and 5-azacitidine on progression free survival comparing patients with N2 lymph nodes categorized as methylated pre-treatment with those who are categorized as unmethylated.
V. To establish factors that predict clinical outcome in patients treated with combination epigenetic therapy by performing genome-wide analyses on pre-treatment tumor DNA.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive azacitidine subcutaneously (SC) on days 1-5 and 8-10 and entinostat orally (PO) once daily (QD) on days 3 and 10. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive standard of care.
After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm I (azacitidine, entinostat) | Experimental | Patients receive azacitidine SC on days 1-5 and 8-10 and entinostat PO QD on days 3 and 10. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. |
|
| Arm II (standard of care) | No Intervention | Patients receive standard of care. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Azacitidine | Drug | Given SC |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Disease-free Survival (DFS) | The DFS hazard rate and 95% confidence interval will be reported. At this time, event time distributions for disease-free survival in the two arms will be estimated with the method of Kaplan and Meier and compared using a stratified Cox-proportional hazards model (stratified for stage IA vs IB) with a two-sided alpha of 10%. | 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| Factors That Predict Clinical Outcome in Patients Treated With Combination Epigenetic Therapy in Terms of Epigenomic Data Generated From the Illumina Platform | The study was terminated early due to poor accrual since the requirement of clinic administration of the 5AZA daily and post-operative patients not wanting 6 months of treatment. For this reason, 13 pts were enrolled and data was not analyzed, for which we are unable to make any conclusions or report results. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Charles Rudin | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| USC / Norris Comprehensive Cancer Center | Los Angeles | California | 90033 | United States | ||
| Moffitt Cancer Center |
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| ID | Title | Description |
|---|---|---|
| FG000 | Azacitidine SC and Entinostat Oral | Patients receive azacitidine SC on days 1-5 and 8-10 and entinostat PO QD on days 3 and 10. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. |
| FG001 | Chemotherapy Alone |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Entinostat | Drug | Given PO |
|
|
| Laboratory Biomarker Analysis | Other | Correlative studies |
|
| Up to 2 years |
| Median Disease-free Survival | Determined by the method determined by Kaplan and Meier. Estimated with 95% confidence intervals. Cox proportional hazard modeling will be used for multivariate analysis. | Up to 5 years |
| Number of Relapses and Deaths Per Total Time of Follow-up Comparing Patients With N2 Lymph Nodes in Terms of Methylated and Unmethylated | Kaplan Meier curves will be used. | Up to 5 years |
| Overall Survival | Determined by the method determined by Kaplan and Meier. Estimated with 95% confidence intervals. Cox proportional hazard modeling will be used for multivariate analysis. | Up to 5 years |
| Presence of Methylation Patterns | McNemar's test will be used to compare the change in methylation after treatment in sputum. | Up to 2 years |
| Toxicities Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0 | Simple descriptive statistics will be utilized to display the data. | Up to 5 years |
| Tampa |
| Florida |
| 33612 |
| United States |
| Anne Arundel Medical Center | Annapolis | Maryland | 21401 | United States |
| Greater Baltimore Medical Center | Baltimore | Maryland | 21204 | United States |
| Johns Hopkins Bayview Medical Center | Baltimore | Maryland | 21224 | United States |
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital | Baltimore | Maryland | 21231 | United States |
| University of Pittsburgh Cancer Institute | Pittsburgh | Pennsylvania | 15232 | United States |
| Vanderbilt-Ingram Cancer Center | Nashville | Tennessee | 37232 | United States |
| University of Texas Southwestern Medical Center | Dallas | Texas | 75390 | United States |
Standard of care chemotherapy |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Azacitidine SC and Entinostat PO | Patients receive azacitidine SC on days 1-5 and 8-10 and entinostat PO QD on days 3 and 10. Followed by Cytotoxic Therapy investigator Choice |
| BG001 | Cytotoxic Therapy | Standard of care |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Study stopped due to early stopping rule | Count of Participants | Participants |
| |||||||||||||||||
| Age, Continuous | Mean | Full Range | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Disease-free Survival (DFS) | The DFS hazard rate and 95% confidence interval will be reported. At this time, event time distributions for disease-free survival in the two arms will be estimated with the method of Kaplan and Meier and compared using a stratified Cox-proportional hazards model (stratified for stage IA vs IB) with a two-sided alpha of 10%. | The study was terminated early due to poor accrual since the requirement of clinic administration of the 5AZA daily and post-operative patients not wanting 6 months of treatment. Data was not collected to assess this outcome measure. | Posted | 3 years |
|
| ||||||||||||||||||||||
| Secondary | Factors That Predict Clinical Outcome in Patients Treated With Combination Epigenetic Therapy in Terms of Epigenomic Data Generated From the Illumina Platform | The study was terminated early due to poor accrual since the requirement of clinic administration of the 5AZA daily and post-operative patients not wanting 6 months of treatment. For this reason, 13 pts were enrolled and data was not analyzed, for which we are unable to make any conclusions or report results. | The study was terminated early due to poor accrual since the requirement of clinic administration of the 5AZA daily and post-operative patients not wanting 6 months of treatment. Data was not collected to assess this outcome measure. | Posted | Up to 2 years |
|
| ||||||||||||||||||||||
| Secondary | Median Disease-free Survival | Determined by the method determined by Kaplan and Meier. Estimated with 95% confidence intervals. Cox proportional hazard modeling will be used for multivariate analysis. | The study was terminated early due to poor accrual since the requirement of clinic administration of the 5AZA daily and post-operative patients not wanting 6 months of treatment. Data was not collected to assess this outcome measure. | Posted | Up to 5 years |
|
| ||||||||||||||||||||||
| Secondary | Number of Relapses and Deaths Per Total Time of Follow-up Comparing Patients With N2 Lymph Nodes in Terms of Methylated and Unmethylated | Kaplan Meier curves will be used. | The study was terminated early due to poor accrual since the requirement of clinic administration of the 5AZA daily and post-operative patients not wanting 6 months of treatment. Data was not collected to assess this outcome measure. | Posted | Up to 5 years |
|
| ||||||||||||||||||||||
| Secondary | Overall Survival | Determined by the method determined by Kaplan and Meier. Estimated with 95% confidence intervals. Cox proportional hazard modeling will be used for multivariate analysis. | The study was terminated early due to poor accrual since the requirement of clinic administration of the 5AZA daily and post-operative patients not wanting 6 months of treatment. Data was not collected to assess this outcome measure. | Posted | Up to 5 years |
|
| ||||||||||||||||||||||
| Secondary | Presence of Methylation Patterns | McNemar's test will be used to compare the change in methylation after treatment in sputum. | The study was terminated early due to poor accrual since the requirement of clinic administration of the 5AZA daily and post-operative patients not wanting 6 months of treatment. Data was not collected to assess this outcome measure. | Posted | Up to 2 years |
|
| ||||||||||||||||||||||
| Secondary | Toxicities Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0 | Simple descriptive statistics will be utilized to display the data. | The study was terminated early due to poor accrual since the requirement of clinic administration of the 5AZA daily and post-operative patients not wanting 6 months of treatment. Data was not collected to assess this outcome measure. | Posted | Up to 5 years |
|
|
Up to 3 years
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Azacitidine SC and Entinostat PO | Patients receive azacitidine SC on days 1-5 and 8-10 and entinostat PO QD on days 3 and 10. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. | 0 | 7 | 0 | 7 | 0 | 7 |
| EG001 | Cytotoxic Chemotherapy | Investigators Choice Chemotherapy | 0 | 6 | 0 | 6 | 0 | 6 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Charlie Rudin, MD | SKCCC | 646.888.4527 | rudinc@mskcc.org |
| ID | Term |
|---|---|
| D002289 | Carcinoma, Non-Small-Cell Lung |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| D001374 | Azacitidine |
| C118739 | entinostat |
| ID | Term |
|---|---|
| D001372 | Aza Compounds |
| D009930 | Organic Chemicals |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012263 | Ribonucleosides |
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| >=65 years |
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| Male |
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|