Neuroendocrine TumorsPhase 2NCT03211988
Entinostat Neuroendocrine (NE) Tumor
A Phase 2 study testing Entinostat in people with Neuroendocrine Tumors, run by Antonio Fojo at 1 site in United States.
Trial summary
This is an open-label, single arm, multi-center Phase II trial of entinostat given as a 5 mg oral dose every week (days 1, 8, 15, and 22 of a 4-week cycle) in patients with relapsed or refractory abdominal neuroendocrine (NE) tumors. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Neuroendocrine Tumors
- What is being tested?
- Entinostat
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Dec 2017to 6 Oct 2021
- 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 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Pathologically confirmed stage intravenous (IV) unresectable relapsed, or unresectable refractory abdominal neuroendocrine tumor from the last biopsy available which may be the initial diagnostic biopsy.
- Relapsed disease is defined as progressive disease following systematic therapy with lanreotide or equivalent and either Sunitinib or everolimus or both. Refractory disease is defined as disease not responding to or having progressed within 1 month of the last dose of most recent systemic therapy to include lanreotide or an analog and either sunitinib or everolimus. (Note, small cell carcinoma and large cell undifferentiated neuroendocrine tumors will be excluded from this trial).
- Eligibility for stage 2 of the study, if the extension stage is opened, will be determined by ribonucleic acid-sequencing (RNA-seq) analysis and master regulator profile of a single fresh needle biopsy specimen obtained during study screening.
- Documented disease that is radiographically measurable.
- Last dose of prior therapy must be > 21 days before the first dose of study drug administration. There is no upper limit to number of prior therapies. However, the patient must have recovered from acute toxicities from the most recent therapy to grade 1 or less.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (must be done within 7 days prior to study drug administration).
Show all 15Show fewer
- Age 18 years or older
- Total Bilirubin ≤ 1.5 x Upper Limit of Normal (ULN) and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x ULN (results within 7 days before study drug administration), ≤5×ULN for patients with liver metastases.
- Serum creatinine ≤ 1.5 x ULN (results within 7 days before study drug administration)
- Absolute neutrophil counts of ≥ 1500/μL (without growth factor support), platelet counts ≥100,000/μL (without transfusion support); and hemoglobin ≥9 g/dL results within 7 days before study drug administration.
- Patients or their legal representative must be able to read, understand, and sign a written informed consent
- International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5×ULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants and activated partial Thromboplastin Time (aPTT) ≤1.5×ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
- If a female of childbearing potential, has a negative serum blood pregnancy test during screening and a negative urine pregnancy test within 3 days prior to receiving the first dose of study drug. If the screening serum test is done within 3 days prior to receiving the first dose of study drug, a urine test is not required. Note: Women of childbearing potential (WoCP) are any women between menarche and menopause who have not been permanently or surgically sterilized and are capable of procreation. Permanent sterilization includes hysterectomy and/or bilateral oophorectomy and/or bilateral salpingectomy but excludes bilateral tubal occlusion. WoCP include non-women who have experienced menopause onset < 12 months prior to enrollment.
- If a female of childbearing potential, willing to use 2 methods of birth control or willing to abstain from heterosexual activity for the course of the study through 120 days after the last dose of study drug.
- If male, agrees to use an adequate method of contraception starting with the first dose of study drug through 120 days after the last dose of study drug.
Who cannot join
- Patients fulfilling any of the following criteria will not be admitted into the study:
- Patients with another active cancer (excluding basal cell carcinoma or cervical intraepithelial neoplasia (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.
- Pregnant or lactating women. Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test documented within 3 days prior to start of study drug.
- Patients with uncontrolled intercurrent illness, active or uncontrolled infections, or a fever >38.5°C that has not been evaluated for infection up to the day of initial dosing. Patients with documented history of tumor fever are accepted provided acute or chronic infection has been excluded as possible cause of the fever.
- Patients who have been treated with any investigational drug within 28 days prior to the first dose of study medication, or who are receiving concurrent treatment with other experimental drugs or anti-cancer therapy.
- Prior treatment with histone deacetylase (HDAC) inhibitors (e.g. valproic acid, Zolinza® (SAHA), romidepsin (Istodax®).
Show all 15Show fewer
- History of pericarditis or pericardial effusion that had required medical or surgical intervention in the last 6 months, or myocardial infarction or arterial thromboembolic events within 6 months, or experiencing severe or unstable angina, or New York Heart Association (NYHA) Class III or IV disease, or a corrected QT (QTc) interval >0.47 seconds
- Known human immunodeficiency virus (HIV) or a history of active Hepatitis B or C as evidenced by laboratory abnormalities in addition to positive serology. Testing is not required for patients not suspected of having these conditions
- Any condition (e.g., known or suspected poor compliance, psychological instability, geographical location, etc) that, in the judgment of the investigator, may affect the patient's ability to sign the informed consent and comply with study procedures
- Any condition that will put the patient at undue risk or discomfort as a result of adherence to study procedures
- Presence or history of brain metastases.
- Uncontrolled hypertension or diabetes mellitus
- Any contraindication to oral agents or significant nausea and vomiting, malabsorption, or significant small bowel resection that, in the opinion of the investigator, would preclude adequate absorption.
- Allergy to benzamide or inactive components of entinostat.
- Patients may not be taking any corticosteroid for any reason while on study and all corticosteroids must be stopped two weeks prior to initiation of study drug.
Trial locations and contacts
1 site in 1 country.
United States1 site
Columbia University Irving Medical Center
New York, New York, 10032
About this study
Official title: A Phase 2 Single-Arm Multicenter Study of Entinostat in Patients With Relapsed or Refractory Abdominal Neuroendocrine (NE) Tumors
This is an open-label, single arm, multi-center Phase II trial of entinostat given as a 5 mg oral dose every week (days 1, 8, 15, and 22 of a 4-week cycle) in patients with relapsed or refractory abdominal neuroendocrine (NE) tumors. Patients will continue on treatment until disease progression or intolerable toxicity occurs.
Read the detailed description
Neuroendocrine tumors (NETs) are derived from NE cells that reside widely in the endocrine system and other organs and comprise a heterogeneous group of neoplasms. Because NETs can arise in a broad spectrum of locations they are associated with a broad range of symptoms that may be caused by mass effects and/or by the production of hormones or biogenic amines.
Most recently, entinostat has been shown to down-regulate the number and function of two key immunosuppressive cells, myeloid derived suppressor cells (MDSCs) and regulatory T-cells (Tregs), in the tumor microenvironment thereby enhancing the activity of immune checkpoint inhibition. To date, entinostat has been investigated alone or in combination in >900 patients with cancer in clinical studies, including >600 patients with solid tumors. Entinostat as a single agent has been studied in metastatic melanoma and in combination has been studied in metastatic non-small cell lung cancer (NSCLC), breast cancer, renal cell cancer, and colon cancer.
- Conditions
- Neuroendocrine Tumors
- Being tested
- Entinostat
- Keywords
- abdominal, neuroendocrine tumor, columbia, relapsed, refractory
- Medical subject headings
- Neuroendocrine Tumors, Recurrence
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
Dose is 5 mg orally every week (days 1, 8, 15, and 22) of a 28 day treatment cycle. Study drug should be taken in the morning and on an empty stomach, at least 2 hours after a meal and at least 1 hour before the next meal. Tablets should be taken whole and not crushed.
| Study group | Role | What they receive |
|---|---|---|
| Entinostat | Other | Eligible patients will be enrolled according to Simon's two-stage design. The dose of Entinostat is 5 mg (one tablet) orally, once every week in a 28 day cycle. Receives: Drug: Entinostat |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR)
Objective response defined as complete response (CR) (Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.) and partial response (PR) (at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) and will be determined from each participant's best confirmed response during protocol therapy. Response as evaluated per RECIST 1.1 criteria.
Measured: Up to 44 months
Secondary outcomes (3)
Duration of Progression-Free Survival (PFS)
Time from study enrollment until disease progression or death.
Measured: Up to 45 months
Duration of Overall Survival (OS)
The length of time from either the date of diagnosis or start of treatment that years participants diagnosed with the disease are still alive.
Measured: Up to 45 months
Duration of Response for Participants Who Achieve Complete Response (CR) or Partial Response (PR)
Time from documentation of tumor response to disease progression in participants who achieve CR or PR.
Measured: Up to 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2017
- Study start13 Dec 2017
- Primary completion24 Aug 2021
- Study completion6 Oct 2021
Why it stopped: Lack of funding and drug supply
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Neuroendocrine TumorsStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Simon 2-stage design (optimum version)
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Antonio Fojo
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Antonio Fojo, Columbia University
- Investigators
- Antonio Fojo, MD, PhD, Principal investigator, Columbia University/Herbert Irving Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03211988
- Sponsor's protocol ID
- AAAR1117
- Status last verified
- Feb 2026
- First submitted
- 6 Jul 2017
- Last updated
- 2 Mar 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Jamison JK, Zhou M, Gelmann EP, Luk L, Bates SE, Califano A, Fojo T. Entinostat in patients with relapsed or refractory abdominal neuroendocrine tumors. Oncologist. 2024 Sep 6;29(9):817-e1213. doi: 10.1093/oncolo/oyae118.
PubMed 38886159
Study at a glance
From the registry record, last updated by the sponsor on 2 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Single-Arm Multicenter Study of Entinostat in Patients With Relapsed or Refractory Abdominal Neuroendocrine (NE) Tumors
- ClinicalTrials.gov ID
- NCT03211988
- Acronym / sponsor ID
- AAAR1117
- Conditions
- Neuroendocrine Tumors
- Keywords
- abdominal, neuroendocrine tumor, columbia, relapsed, refractory
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of funding and drug supply
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Antonio FojoUniversity, hospital or other
- Study start
- 13 Dec 2017 (actual)
- Primary completion
- 24 Aug 2021 (actual)
- Study completion
- 6 Oct 2021 (actual)
- First posted
- 11 Jul 2017 (actual)
- Results
- Posted 2 Mar 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open-label, single arm, multi-center Phase II trial of entinostat given as a 5 mg oral dose every week (days 1, 8, 15, and 22 of a 4-week cycle) in patients with relapsed or refractory abdominal neuroendocrine (NE) tumors. Patients will continue on treatment until disease progression or intolerable toxicity occurs.
Detailed description
Neuroendocrine tumors (NETs) are derived from NE cells that reside widely in the endocrine system and other organs and comprise a heterogeneous group of neoplasms. Because NETs can arise in a broad spectrum of locations they are associated with a broad range of symptoms that may be caused by mass effects and/or by the production of hormones or biogenic amines.
Most recently, entinostat has been shown to down-regulate the number and function of two key immunosuppressive cells, myeloid derived suppressor cells (MDSCs) and regulatory T-cells (Tregs), in the tumor microenvironment thereby enhancing the activity of immune checkpoint inhibition. To date, entinostat has been investigated alone or in combination in >900 patients with cancer in clinical studies, including >600 patients with solid tumors. Entinostat as a single agent has been studied in metastatic melanoma and in combination has been studied in metastatic non-small cell lung cancer (NSCLC), breast cancer, renal cell cancer, and colon cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Simon 2-stage design (optimum version)
| Arm | Type | Receives |
|---|---|---|
| Entinostat | Other | Drug: EntinostatEligible patients will be enrolled according to Simon's two-stage design. The dose of Entinostat is 5 mg (one tablet) orally, once every week in a 28 day cycle. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Pathologically confirmed stage intravenous (IV) unresectable relapsed, or unresectable refractory abdominal neuroendocrine tumor from the last biopsy available which may be the initial diagnostic biopsy.
- Relapsed disease is defined as progressive disease following systematic therapy with lanreotide or equivalent and either Sunitinib or everolimus or both. Refractory disease is defined as disease not responding to or having progressed within 1 month of the last dose of most recent systemic therapy to include lanreotide or an analog and either sunitinib or everolimus. (Note, small cell carcinoma and large cell undifferentiated neuroendocrine tumors will be excluded from this trial).
- Eligibility for stage 2 of the study, if the extension stage is opened, will be determined by ribonucleic acid-sequencing (RNA-seq) analysis and master regulator profile of a single fresh needle biopsy specimen obtained during study screening.
- Documented disease that is radiographically measurable.
- Last dose of prior therapy must be > 21 days before the first dose of study drug administration. There is no upper limit to number of prior therapies. However, the patient must have recovered from acute toxicities from the most recent therapy to grade 1 or less.
Key exclusion criteria (15 listed)
- Patients with another active cancer (excluding basal cell carcinoma or cervical intraepithelial neoplasia (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.
- Pregnant or lactating women. Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test documented within 3 days prior to start of study drug.
- Patients with uncontrolled intercurrent illness, active or uncontrolled infections, or a fever >38.5°C that has not been evaluated for infection up to the day of initial dosing. Patients with documented history of tumor fever are accepted provided acute or chronic infection has been excluded as possible cause of the fever.
- Patients who have been treated with any investigational drug within 28 days prior to the first dose of study medication, or who are receiving concurrent treatment with other experimental drugs or anti-cancer therapy.
- Prior treatment with histone deacetylase (HDAC) inhibitors (e.g. valproic acid, Zolinza® (SAHA), romidepsin (Istodax®).
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-275Dose is 5 mg orally every week (days 1, 8, 15, and 22) of a 28 day treatment cycle. Study drug should be taken in the morning and on an empty stomach, at least 2 hours after a meal and at least 1 hour before the next meal. Tablets should be taken whole and not crushed. | Drug | Entinostat |
Primary outcome
Objective Response Rate (ORR)
Time frame: Up to 44 months
Objective response defined as complete response (CR) (Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.) and partial response (PR) (at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) and will be determined from each participant's best confirmed response during protocol therapy. Response as evaluated per RECIST 1.1 criteria.
3 secondary outcomes
Duration of Progression-Free Survival (PFS)
Time frame: Up to 45 months
Duration of Overall Survival (OS)
Time frame: Up to 45 months
Duration of Response for Participants Who Achieve Complete Response (CR) or Partial Response (PR)
Time frame: Up to 4 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Mar 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38886159Jamison JK, Zhou M, Gelmann EP, Luk L, Bates SE, Califano A, Fojo T. Entinostat in patients with relapsed or refractory abdominal neuroendocrine tumors. Oncologist. 2024 Sep 6;29(9):817-e1213. doi: 10.1093/oncolo/oyae118.
- Individual participant dataSharing planned: No
Related trials for Neuroendocrine Tumors
Active, not recruitingPhase 1/2
A Beta-only IL-2 ImmunoTherapY Study
Advanced Solid Tumor, Unresectable Solid Tumor
RecruitingPhase 1/2
Hepzato Kit and Opdualag for Metastatic Melanoma and Liver Metastasis
Metastatic Melanoma, Liver Metastases
Not yet recruitingObservational study
Clinical Genetics Branch Eligibility Screening Survey
Melanoma, Li-Fraumeni Syndrome
RecruitingPhase 4
Safety and Efficacy of Belzutifan in Preoperative Preparation for Patients With Pheochromocytoma/Paraganglioma (PPGL)
Pheochromocytoma and Paraganglioma (PPGL)
RecruitingPhase 1
A Study of BI 3810944 in Patients With Advanced Cancer
Solid Tumours, Melanoma
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.
Antonio Fojo, MD, PhD principal investigator
Columbia University/Herbert Irving Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Entinostat in people with Neuroendocrine Tumors, run by Antonio Fojo at 1 site 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 15 inclusion and 15 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 2 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 2 Mar 2026). 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?
Objective Response Rate (ORR) (time frame: Up to 44 months). 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 NCT03211988, 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 2 Mar 2026.