Stage IA Non-Small Cell Lung CarcinomaPhase 2NCT01207726
Azacitidine and Entinostat in Treating Patients With Stage I Non-Small Cell Lung Cancer That Has Been Removed By Surgery
A Phase 2 study testing Azacitidine, Entinostat and Laboratory Biomarker Analysis in people with Stage IA Non-Small Cell Lung Carcinoma and Stage IB Non-Small Cell Lung Carcinoma, run by National Cancer Institute (NCI) at 9 sites in United States.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stage IA Non-Small Cell Lung Carcinoma, Stage IB Non-Small Cell Lung Carcinoma
- What is being tested?
- Azacitidine, Entinostat and Laboratory Biomarker Analysis
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 9 sitesUnited States
- Study dates
- Sep 2010to May 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must be status post complete (R0) surgical resection of pathologically-proven NSCLC (stage IA-IB according to AJCC version 7)
- Patients must be at least 4 weeks out from completion of surgery
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Absolute neutrophil count >= 1,000/mcL
- Platelets >= 100,000/mcL
- Total bilirubin =< 1.5 X institutional upper limit of normal
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- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
- Creatinine =< 1.5 X institutional upper limit of normal
- The effects of entinostat and 5-azacitidine on the developing human fetus at the recommended therapeutic dose are unknown; for this reason, 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
Who cannot join
- Patients must be within 8 weeks of completing surgery
- Patients who have received prior chemotherapy or radiation for treatment of their current diagnosis of lung cancer
- Patients with sub-lobar resections (ie: wedge resection or segmentectomy)
- Patients without mediastinal lymph node specimens from mediastinoscopy or surgery (at least level R4 or 7 for right sided tumors OR at least level 5, 6 or 7 for left sided tumors)
- Patients may not be receiving any other investigational agents
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to entinostat, 5-azacitidine or other agents used in the study
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- 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 because entinostat and 5-azacitidine are agents with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with entinostat or 5-azacitidine, breastfeeding should be discontinued if the mother is treated on this protocol; these potential risks may also apply to other agents used in this study
- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with entinostat or 5-azacitidine; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
Anne Arundel Medical Center
Annapolis, Maryland, 21401
Greater Baltimore Medical Center
Baltimore, Maryland, 21204
Johns Hopkins Bayview Medical Center
Baltimore, Maryland, 21224
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital
Baltimore, Maryland, 21231
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, 15232
Moffitt Cancer Center
Tampa, Florida, 33612
About this study
Official title: Randomized Phase II Trial of Adjuvant Combined Epigenetic Therapy With 5-Azacitidine and Entinostat in Resected Stage I Non-small Cell Lung Cancer Versus Standard Care
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).
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- 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.
- Being tested
- Azacitidine, Entinostat, Laboratory Biomarker Analysis
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzacitidineDrug
Also called 5 AZC, 5-AC, 5-Azacytidine, 5-AZC
Given SC
EntinostatDrug
Also called HDAC inhibitor SNDX-275, MS 27-275, MS-275, SNDX-275
Given PO
Laboratory Biomarker AnalysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Azacitidine; Drug: Entinostat; Other: Laboratory Biomarker Analysis |
| Arm II (standard of care) | No intervention | Patients receive standard of care. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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%.
Measured: 3 years
Secondary outcomes (6)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to 5 years
Presence of Methylation Patterns
McNemar's test will be used to compare the change in methylation after treatment in sputum.
Measured: 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.
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2010 (estimated)
- Study startSep 2010
- Primary completionMay 2013
- Study completionMay 2013
Why it stopped: Slow Accrual due to patients not wanting daily clinic administration of 5AZA and/or 6 months of treatment after surgery.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Stage IA Non-Small Cell Lung CarcinomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Charles Rudin, Principal investigator, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01207726
- Sponsor's protocol ID
- NCI-2012-02901
- Other IDs
- NCI-2012-02901, NA_00038631, J1037, 8311, P30CA006973
- Status last verified
- Jan 2019
- First submitted
- 10 Sep 2010
- Last updated
- 5 Feb 2019
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Phase II Trial of Adjuvant Combined Epigenetic Therapy With 5-Azacitidine and Entinostat in Resected Stage I Non-small Cell Lung Cancer Versus Standard Care
- ClinicalTrials.gov ID
- NCT01207726
- Acronym / sponsor ID
- NCI-2012-02901
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow Accrual due to patients not wanting daily clinic administration of 5AZA and/or 6 months of treatment after surgery.
- Enrolment
- 13 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Sep 2010
- Primary completion
- May 2013 (actual)
- Study completion
- May 2013 (actual)
- First posted
- 23 Sep 2010 (estimated)
- Results
- Posted 5 Feb 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (azacitidine, entinostat) | Experimental | Drug: Azacitidine, Drug: Entinostat, Other: Laboratory Biomarker AnalysisPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Patients must be status post complete (R0) surgical resection of pathologically-proven NSCLC (stage IA-IB according to AJCC version 7)
- Patients must be at least 4 weeks out from completion of surgery
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Absolute neutrophil count >= 1,000/mcL
- Platelets >= 100,000/mcL
Key exclusion criteria (9 listed)
- Patients must be within 8 weeks of completing surgery
- Patients who have received prior chemotherapy or radiation for treatment of their current diagnosis of lung cancer
- Patients with sub-lobar resections (ie: wedge resection or segmentectomy)
- Patients without mediastinal lymph node specimens from mediastinoscopy or surgery (at least level R4 or 7 for right sided tumors OR at least level 5, 6 or 7 for left sided tumors)
- Patients may not be receiving any other investigational agents
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AzacitidineAlso: 5 AZC, 5-AC, 5-Azacytidine, 5-AZCGiven SC | Drug | Arm I (azacitidine, entinostat) |
| EntinostatAlso: HDAC inhibitor SNDX-275, MS 27-275, MS-275, SNDX-275Given PO | Drug | Arm I (azacitidine, entinostat) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Arm I (azacitidine, entinostat) |
Primary outcome
Disease-free Survival (DFS)
Time frame: 3 years
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%.
6 secondary outcomes
Factors That Predict Clinical Outcome in Patients Treated With Combination Epigenetic Therapy in Terms of Epigenomic Data Generated From the Illumina Platform
Time frame: Up to 2 years
Median Disease-free Survival
Time frame: 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
Time frame: Up to 5 years
Overall Survival
Time frame: Up to 5 years
Presence of Methylation Patterns
Time frame: Up to 2 years
Toxicities Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0
Time frame: Up to 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Charles Rudin principal investigator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Azacitidine, Entinostat and Laboratory Biomarker Analysis in people with Stage IA Non-Small Cell Lung Carcinoma and Stage IB Non-Small Cell Lung Carcinoma, run by National Cancer Institute (NCI) at 9 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 5 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Feb 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease-free Survival (DFS) (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Feb 2019.