Lung CancerPhase 1ENCORE110NCT01594398
Study to Assess Food Effect on Pharmacokinetics of Entinostat in Subjects With Breast Cancer or Non-Small Cell Lung Cancer
A Phase 1 study testing entinostat, Erlotinib and Exemestane in people with Lung Cancer and Non Small Cell Lung Cancer (NSCLC), run by Syndax Pharmaceuticals at 3 sites in United States.
Trial summary
The purpose of this study is to evaluate the effect of food on the pharmacokinetics (PK) of the experimental drug, entinostat, in women with breast cancer and men and women with non-small cell lung cancer. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Lung Cancer, Non Small Cell Lung Cancer (NSCLC), Breast Cancer
- What is being tested?
- entinostat, Erlotinib and Exemestane
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 3 sitesUnited States
- Study dates
- May 2012to May 2014
- 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 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Breast Cancer Patients Only
- Postmenopausal female patients
- Histologically or cytologically confirmed ER+ breast cancer at initial diagnosis and now has current disease progression and is a candidate to receive exemestane
- NSCLC Patients Only:
- Cytologically or histologically confirmed NSCLC of stage IIIb or IV
- Received 1 to 2 prior chemotherapy or chemoradiotherapy regimens for advanced NSCLC (excluding erlotinib and valproic acid) and now has disease progression and is a candidate to receive erlotinib
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- All Patients:
- Age ≥ 18 years
- Patient must have the following laboratory parameters at study screening: Hemoglobin ≥ 9.0 g/dL; unsupported platelets ≥ 100.0 10-9/L; ANC ≥ 2.0 x 10-9/L; Creatinine less than 2.5 times the upper limit of normal for the institution; AST and alanine transaminase (ALT) < 2.5 times the upper limit of normal for the institution
- Patients may have a history of brain metastasis as long as certain criteria are met
Who cannot join
- Pregnant or lactating women
- Patient has rapidly progressive or life-threatening metastases.
- Patient has had previous treatment with entinostat or any other HDAC inhibitor including valproic acid
- Patient has a concomitant medical condition that precludes adequate study treatment compliance or assessment, or increases patient risk in the opinion of the investigator, such as but not limited to:
- MI or arterial thromboembolic events within 6 months, or experiencing severe or unstable angina, New York Heart Association (NYHA) Class III or IV disease and a QTc interval > 0.47 seconds.
- Uncontrolled heart failure or hypertension, uncontrolled diabetes mellitus, uncontrolled systemic infection.
- Patients with another active cancer (excluding adequately treated basal cell carcinoma or cervical intraepithelial neoplasia [CIN / cervical carcinoma in situ] or melanoma in situ). Prior history of other cancer is allowed, as long as there is no active disease within the prior 5 years.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
Peggy and Charles Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104
Florida Cancer Specialists
Sarasota, Florida, 34232
About this study
Official title: A Phase I Study to Assess the Food Effect on the Pharmacokinetics of Entinostat in Postmenopausal Women With Locally Recurrent or Metastatic ER+ Breast Cancer and Men and Women With Progressive Non-Small Cell Lung Cancer
The purpose of this study is to evaluate the effect of food on the pharmacokinetics (PK) of the experimental drug, entinostat, in women with breast cancer and men and women with non-small cell lung cancer. The safety and tolerability of entinostat will also be evaluated when entinostat is given by itself as well as with the approved drugs, exemestane (Aromasin®) or erlotinib (Tarceva®). A biomarker (chemical "marker" in the blood/tissue that may be related to your response to the study drug) will also be tested.
Read the detailed description
This is Phase 1, randomized, open-label, study of entinostat. The study is designed to evaluate any food effect on the pharmacokinetics of entinostat.
Patients will be randomized to receive entinostat with or without food on Cycle 1 Day 1 (C1D1). Patients randomized to receive entinostat with food on C1D1 will receive a second dose of entinostat without food on Cycle 1 Day 15 (C1D15). Patients randomized to receive entinostat without food on C1D1 will receive a second dose of entinostat with food on C1D15. Each cycle in the study will be for 28 days duration. Blood samples will be obtained pre-dose and serial blood samples will be taken after each dose to assess pharmacokinetics. For Cycle 2 and all subsequent cycles, all patients will continue to receive entinostat on Days 1 and 15 of each cycle. Those with breast cancer will also receive exemestane orally once daily starting on Cycle 2 Day 1. Those with NSCLC will also receive erlotinib starting on Cycle 2 Day 1.
Patients will be assessed at screening and at pre-prescribed times during study enrollment using standard assessments. Patients will also be assessed for tumor response after each 2 cycles. Patients will continue receiving study treatment until tumor progression or adverse events occur which necessitate discontinuing therapy as determined by the Investigator.
- Conditions
- Lung Cancer, Non Small Cell Lung Cancer (NSCLC), Breast Cancer, Estrogen Receptor Breast Cancer
- Being tested
- entinostat, Erlotinib, Exemestane
- Keywords
- carcinoma,non small cell lung, lung diseases, lung neoplasms, Respiratory, Carcinoma, Bronchogenic, Bronchial Neoplasms, Respiratory Tract Neoplasms, Thoracic Neoplasms, Neoplasms by Site, Respiratory Tract Diseases, Erlotinib, Protein Kinase Inhibitors, Breast Neoplasms, Neoplasms, Breast Diseases, Exemestane, Aromatase Inhibitors
- Medical subject headings
- Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Breast Neoplasms, Lung Diseases, Carcinoma, Bronchogenic, Bronchial Neoplasms, Respiratory Tract Neoplasms, Thoracic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
entinostatDrug
Also called SNDX-275, MS-275
10 mg, po, q14 days, until progression or intolerable toxicity
entinostatDrug
Also called SNDX-275, MS-275
10 mg, po, q14 days, until progression or intolerable toxicity
ErlotinibDrug
Also called Tarceva
Erlotinib: NSCLC pts beginning C2D1,150 mg, po, qd.
ErlotinibDrug
Also called Tarceva
Erlotinib: NSCLC pts beginning C2D1,150 mg, po, qd.
ExemestaneDrug
Also called Aromasin
Exemestane: Breast cancer pts beginning C2D1,25 mg, po, qd.
ExemestaneDrug
Also called Aromasin
Exemestane: Breast cancer pts beginning C2D1,25 mg, po, qd.
| Study group | Role | What they receive |
|---|---|---|
| entinostat C1D1 fed | Experimental | Entinostat: Beginning C1D1 fed; C1D15 fasted. Erlotinib: NSCLC pts beginning C2D1,150 mg, po, qd. Exemestane: Breast cancer pts beginning C2D1,25 mg, po, qd. Receives: Drug: entinostat; Drug: Erlotinib; Drug: Exemestane |
| entinostat C1D1 fasted | Experimental | Entinostat: Beginning C1D1 fasted; C1D15 fed. Erlotinib: NSCLC pts beginning C2D1,150 mg, po, qd. Exemestane: Breast cancer pts beginning C2D1,25 mg, po, qd. Receives: Drug: entinostat; Drug: Erlotinib; Drug: Exemestane |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in pharmacokinetics of entinostat when subjects fed or fasted
The pharmacokinetics of entinostat will be analyzed from patient plasma samples: maximum plasma concentration, time of maximum plasma concentration, area under the plasma concentration-time curve from baseline to last measurable concentration and extrapolated to infinity, terminal elimination rate constant.
Measured: C1D1 (sequential), D2, 4, 6, 8, 11; C1D15 (sequential), 16, 18, 20, 22 25; C2D1
Secondary outcomes (4)
Change in laboratory values from baseline
Chemistry, hematology blood samples: changes from baseline will be evaluated.
Measured: Screening, C1D1, C1D15, C2D1, C3D1
Change in ECG results from baseline
Changes from baseline will be evaluated including analysis of QTc prolongation and QTc change from baseline.
Measured: Screening, C1D1 (sequential), D2, 4, 6, 8, 11; C1D15 (sequential), D16, 18, 20, 22, 25; C2D1; EOT
Difference in pharmacodynamics from baseline
Blood samples will be analyzed for changes from baseline in protein lysine acetylation as measured by peripheral blood monocytes. The food effect, changes after entinostat, and changes after exemestane and erlotinib will be evaluated.
Measured: C1D1, D2, D8; C1D15, D16, D22; C2D1; C3D1; EOT
Adverse events
Incidence of treatment emergent adverse events, serious adverse events, adverse events resulting in permanent discontinuation of study drug, and deaths occurring within 30-days of the last dose of study drug.
Measured: C1D1 , D2, 4, 6, 8, 11; C1D15, 16, 18, 20, 22 25; C2D1; D1 of each subsequent cycle through end of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2012 (estimated)
- Study startMay 2012
- Primary completionApr 2014
- Study completionMay 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Lung CancerStudies of the same condition, open and under way.
- 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
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Syndax Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- William McCulloch, M.D., Study director, Syndax PharmaceuticalsHoward A Burris, M.D., Principal investigator, Tennessee Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01594398
- Sponsor's protocol ID
- SNDX-275-0110
- Acronym
- ENCORE110
- Status last verified
- Nov 2021
- First submitted
- 4 May 2012
- Last updated
- 19 Nov 2021
- Results posted
- No
- Data monitoring committee
- No
Publications
Witta SE, Jotte RM, Konduri K, Neubauer MA, Spira AI, Ruxer RL, Varella-Garcia M, Bunn PA Jr, Hirsch FR. Randomized phase II trial of erlotinib with and without entinostat in patients with advanced non-small-cell lung cancer who progressed on prior chemotherapy. J Clin Oncol. 2012 Jun 20;30(18):2248-55. doi: 10.1200/JCO.2011.38.9411. Epub 2012 Apr 16.
PubMed 22508830
Study at a glance
From the registry record, last updated by the sponsor on 19 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study to Assess the Food Effect on the Pharmacokinetics of Entinostat in Postmenopausal Women With Locally Recurrent or Metastatic ER+ Breast Cancer and Men and Women With Progressive Non-Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT01594398
- Acronym / sponsor ID
- ENCORE110 / SNDX-275-0110
- Conditions
- Lung Cancer, Non Small Cell Lung Cancer (NSCLC), Breast Cancer, Estrogen Receptor Breast Cancer
- Keywords
- carcinoma,non small cell lung, lung diseases, lung neoplasms, Respiratory, Carcinoma, Bronchogenic, Bronchial Neoplasms, Respiratory Tract Neoplasms, Thoracic Neoplasms
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Syndax PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- May 2012
- Primary completion
- Apr 2014 (actual)
- Study completion
- May 2014 (actual)
- First posted
- 9 May 2012 (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.
The purpose of this study is to evaluate the effect of food on the pharmacokinetics (PK) of the experimental drug, entinostat, in women with breast cancer and men and women with non-small cell lung cancer. The safety and tolerability of entinostat will also be evaluated when entinostat is given by itself as well as with the approved drugs, exemestane (Aromasin®) or erlotinib (Tarceva®). A biomarker (chemical "marker" in the blood/tissue that may be related to your response to the study drug) will also be tested.
Detailed description
This is Phase 1, randomized, open-label, study of entinostat. The study is designed to evaluate any food effect on the pharmacokinetics of entinostat.
Patients will be randomized to receive entinostat with or without food on Cycle 1 Day 1 (C1D1). Patients randomized to receive entinostat with food on C1D1 will receive a second dose of entinostat without food on Cycle 1 Day 15 (C1D15). Patients randomized to receive entinostat without food on C1D1 will receive a second dose of entinostat with food on C1D15. Each cycle in the study will be for 28 days duration. Blood samples will be obtained pre-dose and serial blood samples will be taken after each dose to assess pharmacokinetics. For Cycle 2 and all subsequent cycles, all patients will continue to receive entinostat on Days 1 and 15 of each cycle. Those with breast cancer will also receive exemestane orally once daily starting on Cycle 2 Day 1. Those with NSCLC will also receive erlotinib starting on Cycle 2 Day 1.
Patients will be assessed at screening and at pre-prescribed times during study enrollment using standard assessments. Patients will also be assessed for tumor response after each 2 cycles. Patients will continue receiving study treatment until tumor progression or adverse events occur which necessitate discontinuing therapy as determined by the Investigator.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| entinostat C1D1 fed | Experimental | Drug: entinostat, Drug: Erlotinib, Drug: ExemestaneEntinostat: Beginning C1D1 fed; C1D15 fasted. Erlotinib: NSCLC pts beginning C2D1,150 mg, po, qd. Exemestane: Breast cancer pts beginning C2D1,25 mg, po, qd. |
| entinostat C1D1 fasted | Experimental | Drug: entinostat, Drug: Erlotinib, Drug: ExemestaneEntinostat: Beginning C1D1 fasted; C1D15 fed. Erlotinib: NSCLC pts beginning C2D1,150 mg, po, qd. Exemestane: Breast cancer pts beginning C2D1,25 mg, po, qd. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Breast Cancer Patients Only
- Postmenopausal female patients
- Histologically or cytologically confirmed ER+ breast cancer at initial diagnosis and now has current disease progression and is a candidate to receive exemestane
- Cytologically or histologically confirmed NSCLC of stage IIIb or IV
- Received 1 to 2 prior chemotherapy or chemoradiotherapy regimens for advanced NSCLC (excluding erlotinib and valproic acid) and now has disease progression and is a candidate to receive erlotinib
Key exclusion criteria (7 listed)
- Pregnant or lactating women
- Patient has rapidly progressive or life-threatening metastases.
- Patient has had previous treatment with entinostat or any other HDAC inhibitor including valproic acid
- Patient has a concomitant medical condition that precludes adequate study treatment compliance or assessment, or increases patient risk in the opinion of the investigator, such as but not limited to:
- MI or arterial thromboembolic events within 6 months, or experiencing severe or unstable angina, New York Heart Association (NYHA) Class III or IV disease and a QTc interval > 0.47 seconds.
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 |
|---|---|---|
| entinostatAlso: SNDX-275, MS-27510 mg, po, q14 days, until progression or intolerable toxicity | Drug | entinostat C1D1 fed |
| entinostatAlso: SNDX-275, MS-27510 mg, po, q14 days, until progression or intolerable toxicity | Drug | entinostat C1D1 fasted |
| ErlotinibAlso: TarcevaErlotinib: NSCLC pts beginning C2D1,150 mg, po, qd. | Drug | entinostat C1D1 fed |
| ErlotinibAlso: TarcevaErlotinib: NSCLC pts beginning C2D1,150 mg, po, qd. | Drug | entinostat C1D1 fasted |
| ExemestaneAlso: AromasinExemestane: Breast cancer pts beginning C2D1,25 mg, po, qd. | Drug | entinostat C1D1 fed |
| ExemestaneAlso: AromasinExemestane: Breast cancer pts beginning C2D1,25 mg, po, qd. | Drug | entinostat C1D1 fasted |
Primary outcome
Difference in pharmacokinetics of entinostat when subjects fed or fasted
Time frame: C1D1 (sequential), D2, 4, 6, 8, 11; C1D15 (sequential), 16, 18, 20, 22 25; C2D1
The pharmacokinetics of entinostat will be analyzed from patient plasma samples: maximum plasma concentration, time of maximum plasma concentration, area under the plasma concentration-time curve from baseline to last measurable concentration and extrapolated to infinity, terminal elimination rate constant.
4 secondary outcomes
Change in laboratory values from baseline
Time frame: Screening, C1D1, C1D15, C2D1, C3D1
Change in ECG results from baseline
Time frame: Screening, C1D1 (sequential), D2, 4, 6, 8, 11; C1D15 (sequential), D16, 18, 20, 22, 25; C2D1; EOT
Difference in pharmacodynamics from baseline
Time frame: C1D1, D2, D8; C1D15, D16, D22; C2D1; C3D1; EOT
Adverse events
Time frame: C1D1 , D2, 4, 6, 8, 11; C1D15, 16, 18, 20, 22 25; C2D1; D1 of each subsequent cycle through end of treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Nov 2021.
- Background: PubMed 22508830Witta SE, Jotte RM, Konduri K, Neubauer MA, Spira AI, Ruxer RL, Varella-Garcia M, Bunn PA Jr, Hirsch FR. Randomized phase II trial of erlotinib with and without entinostat in patients with advanced non-small-cell lung cancer who progressed on prior chemotherapy. J Clin Oncol. 2012 Jun 20;30(18):2248-55. doi: 10.1200/JCO.2011.38.9411. Epub 2012 Apr 16.
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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.
William McCulloch, M.D. study director
Syndax Pharmaceuticals
Howard A Burris, M.D. principal investigator
Tennessee Oncology
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 entinostat, Erlotinib and Exemestane in people with Lung Cancer and Non Small Cell Lung Cancer (NSCLC), run by Syndax Pharmaceuticals 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 10 inclusion and 7 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: finished, as of the sponsor's last update on 19 Nov 2021. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Difference in pharmacokinetics of entinostat when subjects fed or fasted (time frame: C1D1 (sequential), D2, 4, 6, 8, 11; C1D15 (sequential), 16, 18, 20, 22 25; C2D1). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01594398, which also lists 1 linked publication.
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 19 Nov 2021.