Stage IA Non-Small Cell Lung CarcinomaPhase 1NCT01886573
Azacitidine and Entinostat in Treating Patients With Newly Diagnosed Stage IA-IIIA Non-Small Lung Cancer Undergoing Surgery
A Phase 1 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 3 sites in United States.
Trial summary
This pilot clinical trials studies azacitidine and entinostat in treating patients with newly diagnosed stage IA-IIIIA non-small cell lung undergoing surgery. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from… 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, Stage IIA Non-Small Cell Lung Carcinoma
- What is being tested?
- Azacitidine, Entinostat and Laboratory Biomarker Analysis
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 3 sitesUnited States
- Study dates
- Jun 2013to Feb 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Undergoing a diagnostic biopsy, including computed tomography (CT)-guided or bronchoscopic for suspected diagnosis of NSCLC
- Able to understand and sign an informed consent discussing the risks and benefits of obtaining a concurrent research biopsy; patients who have a fresh frozen biopsy available secondary to institutional tissue collection protocols may substitute such a biopsy for the study-required pre-treatment biopsy
- Histologically confirmed diagnosis of operable NSCLC that has not been previously treated
- Clinical stage IA-IIIA
- Appropriate candidate for surgical management, in the opinion of the treating thoracic surgeon
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 at the time of initiation of neoadjuvant epigenetic therapy
Show all 14Show fewer
- Absolute neutrophil count > 1,000/mcL
- Platelets > 100,000/mcL
- Total bilirubin < 1.5 x institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 2.5 x institutional ULN
- Creatinine < 1.5 x institutional ULN
- Able to understand and sign an informed consent
- 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
- Both men and women and members of all races and ethnic groups are eligible for this trial; the coordinating center will be responsible for ensuring each participating site is accruing a representative sample consistent with the estimate of population representation in the site's geographical location for race and ethnic groups as determined by the Census Bureau to assure overall target goals are met
Who cannot join
- Patients who have received prior chemotherapy or radiation for their diagnosis of lung cancer
- Patients may not be receiving any other investigational agent
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to entinostat or 5-azacytidine
- 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
- Any co-morbid condition that' in the view of the attending physician' renders the patient at high risk from treatment complications
Show all 10Show fewer
- Human immunodeficiency virus (HIV) positive patients on combination antiretroviral therapy are ineligible
- Known or suspected hypersensitivity to azacitidine or mannitol
- Patients with advanced malignant hepatic tumors
- Use of anti-neoplastic or anti-tumor agents that are not part of the study therapy, including chemotherapy, radiation therapy, immunotherapy, and hormonal anticancer therapy, is not permitted while participating in this study; Note: study participants with stage II or III NSCLC, or stage I NSCLC with tumor size greater than 4 cm, should be offered standard adjuvant platinum-based chemotherapy in accordance with local practice (post-operatively)
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University of New Mexico
Albuquerque, New Mexico, 87106
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536
About this study
Official title: Genome-Wide Methylation and Gene Re-expression Analysis of Resectable Lung Tumor Tissue Pairs Obtained Pre- and Post-Treatment With 5-Azacytidine and Entinostat
This pilot clinical trials studies azacitidine and entinostat in treating patients with newly diagnosed stage IA-IIIIA non-small cell lung undergoing surgery. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Entinostat may stop the growth of cancer tumor cells by blocking some of the enzymes needed for cell growth. Giving azacitidine with entinostat may be an effective treatment for non-small cell lung cancer.
Read the detailed description
PRIMARY OBJECTIVES:
- To measure reversal of aberrant genome-wide promoter methylation and gene re-expression in paired, pre- and post- treatment lung tumor tissue pairs from patients with newly diagnosed, surgically resectable non-small cell lung cancer before and after exposure to a single neoadjuvant cycle of 5-azacytidine (azacitidine) and entinostat.
SECONDARY OBJECTIVES:
- To measure the 3-year disease-free survival of operable non-small cell lung cancer (NSCLC) patients who receive 1 cycle of preoperative epigenetic treatment.
II. To determine any potential toxicities, and reversibility of toxicities, of a single pre-operative cycle of 5-azacytidine and entinostat.
OUTLINE:
Patients receive azacitidine subcutaneously (SC) on days 1-6 and 8-10 and entinostat orally (PO) on days 3 and 10. Patients undergo surgery between days 11-20 (this period can be extended 10 more days if adverse events from therapy impose a surgical risk).
After completion of study treatment, patients are followed up at 4 weeks, every 3 months for 2 years and then every 6 months for 1 year.
- Conditions
- Stage IA Non-Small Cell Lung Carcinoma, Stage IB Non-Small Cell Lung Carcinoma, Stage IIA Non-Small Cell Lung Carcinoma, Stage IIB Non-Small Cell Lung Carcinoma, Stage IIIA Non-Small Cell Lung Cancer
- Being tested
- Azacitidine, Entinostat, Laboratory Biomarker Analysis, Pharmacological Study, Therapeutic Conventional Surgery
- 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
Correlative studies
Therapeutic Conventional SurgeryProcedure or surgery
Undergo surgery
| Study group | Role | What they receive |
|---|---|---|
| Treatment (azacitidine, entinostat) | Experimental | Patients receive azacitidine SC on days 1-6 and 8-10 and entinostat PO on days 3 and 10. Patients undergo surgery between days 11-20 (this period can be extended 10 more days if adverse events from therapy impose a surgical risk). Receives: Drug: Azacitidine; Drug: Entinostat; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Procedure: Therapeutic Conventional Surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in aberrant genome-wide promoter methylation
Genome-wide DNA methylation and gene expression profiles of each pre- and post-treatment tumor will be assessed using validated DNA methylation and gene expression arrays. Response will be measured based on the degree of epigenomic reprogramming (i.e., number of genes affected, degree of demethylation, and class of genes [e.g., PRC2]) and pathways affected.
Measured: Baseline up to day 20
Change in gene expression
Genome-wide DNA methylation and gene expression profiles of each pre- and post-treatment tumor will be assessed using validated DNA methylation and gene expression arrays. Response will be measured based on the degree of epigenomic reprogramming (i.e., number of genes affected, degree of demethylation, and class of genes [e.g., PRC2]) and pathways affected.
Measured: Baseline up to day 20
Secondary outcomes (3)
Disease-free survival
Measured: Up to 3 years
Reversibility of toxicities
Measured: Up to 4 weeks after surgery
Toxicities, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.02
Measured: Up to 4 weeks after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2013 (estimated)
- Study startJun 2013
- Primary completionFeb 2015
- Study completionFeb 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Montaser Shaheen, Principal investigator, University of New Mexico
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01886573
- Sponsor's protocol ID
- NCI-2013-01186
- Other IDs
- NCI-2013-01186, CTEP 9431, INST 1117, 9431, P30CA118100, R21CA161561
- Status last verified
- Nov 2016
- First submitted
- 21 Jun 2013
- Last updated
- 18 Nov 2016
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genome-Wide Methylation and Gene Re-expression Analysis of Resectable Lung Tumor Tissue Pairs Obtained Pre- and Post-Treatment With 5-Azacytidine and Entinostat
- ClinicalTrials.gov ID
- NCT01886573
- Acronym / sponsor ID
- NCI-2013-01186
- Conditions
- Stage IA Non-Small Cell Lung Carcinoma, Stage IB Non-Small Cell Lung Carcinoma, Stage IIA Non-Small Cell Lung Carcinoma, Stage IIB Non-Small Cell Lung Carcinoma, Stage IIIA Non-Small Cell Lung Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Jun 2013
- Primary completion
- Feb 2015 (actual)
- Study completion
- Feb 2015 (actual)
- First posted
- 26 Jun 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This pilot clinical trials studies azacitidine and entinostat in treating patients with newly diagnosed stage IA-IIIIA non-small cell lung undergoing surgery. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Entinostat may stop the growth of cancer tumor cells by blocking some of the enzymes needed for cell growth. Giving azacitidine with entinostat may be an effective treatment for non-small cell lung cancer.
Detailed description
PRIMARY OBJECTIVES:
- To measure reversal of aberrant genome-wide promoter methylation and gene re-expression in paired, pre- and post- treatment lung tumor tissue pairs from patients with newly diagnosed, surgically resectable non-small cell lung cancer before and after exposure to a single neoadjuvant cycle of 5-azacytidine (azacitidine) and entinostat.
SECONDARY OBJECTIVES:
- To measure the 3-year disease-free survival of operable non-small cell lung cancer (NSCLC) patients who receive 1 cycle of preoperative epigenetic treatment.
II. To determine any potential toxicities, and reversibility of toxicities, of a single pre-operative cycle of 5-azacytidine and entinostat.
OUTLINE:
Patients receive azacitidine subcutaneously (SC) on days 1-6 and 8-10 and entinostat orally (PO) on days 3 and 10. Patients undergo surgery between days 11-20 (this period can be extended 10 more days if adverse events from therapy impose a surgical risk).
After completion of study treatment, patients are followed up at 4 weeks, every 3 months for 2 years and then every 6 months for 1 year.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (azacitidine, entinostat) | Experimental | Drug: Azacitidine, Drug: Entinostat, Other: Laboratory Biomarker Analysis, Other: Pharmacological Study, Procedure: Therapeutic Conventional SurgeryPatients receive azacitidine SC on days 1-6 and 8-10 and entinostat PO on days 3 and 10. Patients undergo surgery between days 11-20 (this period can be extended 10 more days if adverse events from therapy impose a surgical risk). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Undergoing a diagnostic biopsy, including computed tomography (CT)-guided or bronchoscopic for suspected diagnosis of NSCLC
- Able to understand and sign an informed consent discussing the risks and benefits of obtaining a concurrent research biopsy; patients who have a fresh frozen biopsy available secondary to institutional tissue collection protocols may substitute such a biopsy for the study-required pre-treatment biopsy
- Histologically confirmed diagnosis of operable NSCLC that has not been previously treated
- Clinical stage IA-IIIA
- Appropriate candidate for surgical management, in the opinion of the treating thoracic surgeon
Key exclusion criteria (10 listed)
- Patients who have received prior chemotherapy or radiation for their diagnosis of lung cancer
- Patients may not be receiving any other investigational agent
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to entinostat or 5-azacytidine
- 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
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 | Treatment (azacitidine, entinostat) |
| EntinostatAlso: HDAC inhibitor SNDX-275, MS 27-275, MS-275, SNDX-275Given PO | Drug | Treatment (azacitidine, entinostat) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (azacitidine, entinostat) |
| Pharmacological StudyCorrelative studies | Other | Treatment (azacitidine, entinostat) |
| Therapeutic Conventional SurgeryUndergo surgery | Procedure or surgery | Treatment (azacitidine, entinostat) |
Primary outcome
Change in aberrant genome-wide promoter methylation
Time frame: Baseline up to day 20
Genome-wide DNA methylation and gene expression profiles of each pre- and post-treatment tumor will be assessed using validated DNA methylation and gene expression arrays. Response will be measured based on the degree of epigenomic reprogramming (i.e., number of genes affected, degree of demethylation, and class of genes [e.g., PRC2]) and pathways affected.
Change in gene expression
Time frame: Baseline up to day 20
Genome-wide DNA methylation and gene expression profiles of each pre- and post-treatment tumor will be assessed using validated DNA methylation and gene expression arrays. Response will be measured based on the degree of epigenomic reprogramming (i.e., number of genes affected, degree of demethylation, and class of genes [e.g., PRC2]) and pathways affected.
3 secondary outcomes
Disease-free survival
Time frame: Up to 3 years
Reversibility of toxicities
Time frame: Up to 4 weeks after surgery
Toxicities, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.02
Time frame: Up to 4 weeks after surgery
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2016.
Related trials for Stage IA Non-Small Cell Lung Carcinoma
Not yet recruitingPhase 2
Study of Robotic Assisted/Image Guided Electromagnetic Navigation Bronchoscopic Therapies and Surgery in Stage IA NSCLC
Stage IA NSCLC
Active, not recruitingObservational study
Treatment Effects on Development of Chemotherapy-Induced Peripheral Neuropathy in Patients With Cancer
Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage IA Breast Cancer AJCC v8
RecruitingPhase 2
An Adjuvant Study to Evaluate SMS001 (Paclitaxel) in Non-Small Cell Lung Cancer
Carcinoma, Non-Small-Cell Lung Cancer (NSCLC)
Active, not recruitingPhase 1/2
Safety, PK and Efficacy of ONC-392 in Monotherapy and in Combination of Anti-PD-1 in Advanced Solid Tumors and NSCLC
Non Small Cell Lung Cancer, Advanced Solid Tumor
Not yet recruitingPhase 1
Evaluate the Safety, Tolerability, and Preliminary Efficacy of EVM14 in Combination With Ivonescimab in Sq-NSCLC Patients
Squamous Non-Small Cell Lung Cancer sqNSCLC
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.
Montaser Shaheen principal investigator
University of New Mexico
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 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 3 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 14 inclusion and 10 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 18 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
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?
Change in aberrant genome-wide promoter methylation (time frame: Baseline up to day 20). The study lists 2 primary outcomes in all. 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 18 Nov 2016.