CompletedNCT02780804Updated Oct 17, 2023Results posted

Entinostat in Treating Pediatric Patients With Recurrent or Refractory Solid Tumors

A Phase 1 interventional study of Entinostat and Laboratory Biomarker Analysis in Brain Stem Neoplasm, Pineal Region Neoplasm and Recurrent Lymphoma, sponsored by National Cancer Institute (NCI). Completed at 21 sites in United States. Open to participants aged 12 Months to 21 Years. Per ClinicalTrials.gov, last updated 2023-10-17.

Sponsored by National Cancer Institute (NCI) · Phase 1, Interventional, and Treatment

Phase: Phase 1
Study type: Interventional
Enrollment: 21
Allocation: Not applicable
Ages: 12 Months to 21 Years
Sex: All

Study summary

This phase I trial studies the side effects and best dose of entinostat in treating pediatric patients with solid tumors that have come back or have not responded to treatment. Entinostat may block some of the enzymes needed for cell division and it may help to kill tumor cells.

Read the detailed description

PRIMARY OBJECTIVES:

I. To estimate the maximum tolerated dose (MTD) and/or recommended phase 2 dose of entinostat administered as a single-agent, once weekly to children with recurrent or refractory solid tumors.

II. To define and describe the toxicities of entinostat administered as a single agent, once weekly to children with recurrent or refractory solid tumors.

III. To characterize the pharmacokinetics of entinostat in children with recurrent or refractory cancer.

SECONDARY OBJECTIVES:

I. To preliminarily define the antitumor activity of entinostat within the confines of a phase 1 study.

II. To assess change in histone H3 and H4 acetylation in peripheral blood mononuclear cells (PBMCs) as a marker of the biologic activity of entinostat.

OUTLINE: This is a dose escalation study.

Patients receive entinostat orally (PO) on days 1, 8, 15, and 22. Cycles repeat every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity.

Conditions studied

Brain Stem Neoplasm
Pineal Region Neoplasm
Recurrent Lymphoma
Recurrent Malignant Solid Neoplasm
Recurrent Primary Central Nervous System Neoplasm
Recurrent Visual Pathway Glioma
Refractory Lymphoma
Refractory Malignant Solid Neoplasm
Refractory Primary Central Nervous System Neoplasm
Refractory Visual Pathway Glioma

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In context

Pinealoma

66 studies on the registry are indexed under Pinealoma; 11 are open to participants now.

This study's enrollment of 21 is below the median of 26 across 43 interventional studies indexed under Pinealoma.

Browse Pinealoma studies →

Lead sponsor

National Cancer Institute (NCI) is the lead sponsor of 3,556 studies on the registry; 336 are open to participants now.

Of its 411 completed or terminated interventional studies of FDA-regulated products, 373 (91%) have results posted.

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Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 12 Months to 21 Years
Sexes eligible: All
Accepts healthy volunteers: No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

Patients must have a body surface area (BSA) of >= 1.17 m\^2 at time of study enrollment
Patients must be able to swallow intact tablets
Patients with recurrent or solid tumors, including central nervous system (CNS) tumors or lymphoma, are eligible; patients must have had histologic verification of at original diagnosis or relapse except in patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG)
Patients must have either measurable or evaluable disease
Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
>= 50% for patients > 16 years of age and Lansky >= 50 for patients =\< 16 years of age; Note: neurologic deficits in patients with CNS tumors must have been relatively stable for at least 7 days prior to study enrollment; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment; if after the required timeframe, the defined eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately
- Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive; the duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment
  - Solid tumor patients: >= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea)
  - Lymphoma patients:
    - a waiting period prior to enrollment is not required for patients receiving standard cytotoxic maintenance chemotherapy (i.e. , vincristine, thioguanine[6MP], and/or methotrexate)
    - >=14 days must have elapsed after the completion of other cytotoxic therapy, with the exception of hydroxyurea, for patients not receiving standard maintenance therapy; additionally, patients must have fully recovered from all acute toxic effects of prior therapy; Note: cytoreduction with hydroxyurea must be discontinued >= 24 hours prior to the start of protocol therapy
- Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced or [ANC] counts): >= 7 days must have elapsed from the last dose of agent; the duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment
- Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =\< 1
- Hematopoietic growth factors: >= 14 days must have elapsed from the last dose of a long-acting growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair and the study-assigned research coordinator
- Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days must have elapsed from the last dose of interleukins, interferon or cytokines (other than hematopoietic growth factors)
- Stem cell infusions (with or without traumatic brain injury [TBI]):
  - Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: >= 84 days must have elapsed from infusion and no evidence of (GVHD)
  - Autologous stem cell infusion including boost infusion: >= 42 days must have elapsed from infusion
- Cellular therapy: >= 42 days must have elapsed from last dose of any type of cellular therapy (e.g. modified T cells, natural killer [NK] cells, dendritic cells, etc.)
- External beam radiation (XRT)/external beam irradiation including protons: >= 14 days must have elapsed after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to 50% of the pelvis; >= 42 days if other substantial bone marrow (BM) radiation
- Radiopharmaceutical therapy (e.g., radiolabeled antibody, iobenguane I-131 [131I-MIBG]): >= 42 days must have elapsed from the last dose of systemically administered radiopharmaceutical therapy
- Histone deacetylase (HDAC) inhibitors: Patients must not have received prior therapy with entinostat; patients who have received therapy with other HDAC inhibitors are eligible
Peripheral absolute neutrophil count (ANC) >= 1000/mm\^3 (within 7 days prior to enrollment)
Platelet count >= 100,000/mm\^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) (within 7 days prior to enrollment)
>= 8.0 g/dl, with or without transfusion (within 7 days prior to enrollment)
Patients with known bone marrow disease will not be eligible
or radioisotope (GFR) >= 70 ml/min/1.73 m\^2 or a serum creatinine based on age/gender as follows:
- 1 to \< 2 years: 0.6 mg/dL for males and females
- 2 to \< 6 years: 0.8 mg/dL for males and females
- 6 to \< 10 years: 1.0 mg/dL for males and females
- 10 to \< 13 years: 1.2 mg/dL for males and females
- 13 to \< 16 years: 1.5 mg/dL for males and 1.4 mg/dL for females
- > = 16 years: 1.7 mg/dL for males and 1.4 mg/dL for females (within 7 days prior to enrollment)
(sum of conjugated + conjugated) =\< 1.5 x (ULN) for age (within 7 days prior to enrollment)
Serum glutamate pyruvate transaminase () (alanine aminotransferase [ALT]) =\< 3 x upper limit of normal (ULN) = 135 U/l; for the purpose of this study, the ULN for SGPT is 45 U/l (within 7 days prior to enrollment)
Serum albumin >= 2 g/dl (within 7 days prior to enrollment)
All patients and/or their parents or legally authorized representatives must sign a written ; assent, when appropriate, will be obtained according to institutional guidelines

Exclusion criteria

Exclusion Criteria:

Pregnant or breast-feeding women will not be entered on this study; pregnancy tests must be obtained in girls who are post-menarchal; males or females of may not participate unless they have agreed to use an effective method both during and for 3 months after participation in this study; abstinence is an acceptable method of contraception; those who become pregnant while on treatment with entinostat must discontinue immediately and consult their treating physician
Patients receiving who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible; if used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
Patients who are currently receiving another drug are not eligible
Patients who are currently receiving other anti-cancer agents are not eligible
Patients requiring concurrent administration of valproic acid are not eligible for this trial
Patients who are receiving cyclosporine, tacrolimus or other agents to prevent post bone marrow transplant are not eligible for this trial
Patients with a BSA ˂ 1.17 m\^2 at time of study enrollment are not eligible
Patients who are not able to swallow intact tablets are not eligible
Patients with a known history of (QTc) prolongation (> 480 msec), or known history of ventricular tachycardia, ventricular fibrillation or Torsades de pointes are not eligible
Patients who have an uncontrolled infection are not eligible
Patients who have received a prior solid organ transplantation are not eligible
Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
Patients with a history of allergy to medications that have a benzamide structure (e.g., metoclopramide, procarbazine, domperidone, cisapride etc.) are not eligible

Terms in these criteria, in plain language(19)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Relapsed and refractory

Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.

Cancer (malignancy)

Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.

Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.

Karnofsky performance status (KPS)

A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.

Studies often ask for 60 or 70 and above. Your doctor gives the score.

Corticosteroids (steroids)

Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.

Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.

Platelets

Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.

Absolute neutrophil count (ANC)

The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.

It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.

GVHD (graft-versus-host disease)

After a transplant from a donor, the donor’s immune cells attack the recipient’s body, often the skin, gut or liver.

Hemoglobin (Hb)

The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).

Metastases

Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.

Creatinine clearance (CrCl)

How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.

GFR and eGFR (kidney filtering)

GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².

Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.

Bilirubin

A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.

Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.

ULN (upper limit of normal)

The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.

“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.

ALT and AST (liver enzymes)

Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.

Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Reproductive potential

Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.

Criteria about it usually ask for contraception during the study and for a time after it.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

Investigational drug or device

A drug or device being studied in a clinical trial.

It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.

QT and QTc

On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.

The study may name a correction formula and a limit in milliseconds, often around 450–480.

Study design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrollment: 21 participants (actual)

Study arms

Experimental
Treatment (entinostat)
Patients receive entinostat PO on days 1, 8, 15, and 22. Cycles repeat every 28 days for up to 5 years in the absence of disease progression or unacceptable toxicity.
Drug: Entinostat · Other: Laboratory Biomarker Analysis · Other: Pharmacological Study

Interventions

DrugEntinostat
Given PO
OtherLaboratory Biomarker Analysis
Correlative studies
OtherPharmacological Study
Correlative studies

What researchers measure

Primary outcomes

Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (R2PD) of Entinostat
The MTD/RP2D will be defined as the maximum dose at which fewer than one-third of patients experience dose limiting toxicity during cycle 1 of therapy among 6 toxicity-evaluable patients. The frequency of cycle 1 dose limiting toxicities will be summarized by dose level among patients in the dose escalation part of the study.
Time frame: Up to 28 days
Frequency of Adverse Events for Entinostat
The frequency of patients with at least one Grade 3 or greater adverse event that are at least possibly attributable to entinostat during cycle 1 will be summarized by study part, dose level.
Time frame: Up to 28 days
Half-life of Entinostat
The median (min, max) Half-Life of entinostat stratified by study part and dose level. The half-life (t1/2) was calculated using the equation t1/2 = 0.693/λz, where the terminal elimination rate constant (λz) was determined from a least-squares regression of the log-transformed plasma concentration vs. time data for the last 3 - 4 time points.
Time frame: Plasma concentrations were measured at 0, 0.5, 1, 3, 6, 24, and 48-96 hours post-dose during cycle 1, day 1.
Peak Plasma Concentration of Entinostat: C-Max
The median (min, max) of the peak plasma concentration of entinostat stratified by study part, dose level. Time points were assessed at 0, 0.5, 1, 3, 6, 24, and 48-96 hours post-dose during cycle 1, day 1.
Time frame: Up to 96 hours
Total Area Under the Plasma Concentration Curve of Entinostat: AUC
The median (min, max) of the total area under the plasma concentration curve of entinostat stratified by study part, dose level. Time points were assessed at 0, 0.5, 1, 3, 6, 24, and 48-96 hours post-dose during cycle 1, day 1.
Time frame: Up to 96 hours
Time to Reach Maximum Plasma Concentration of Entinostat: T-Max
The median (min, max) of the time to reach maximum plasma concentration of entinostat stratified by study part, dose level. Time points were assessed at 0, 0.5, 1, 3, 6, 24, and 48-96 hours post-dose during cycle 1, day 1.
Time frame: Up to 96 hours

Secondary outcomes

Antitumor Activity of Entinostat
Frequency of response to entinostat per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and/or assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR, stratified by study part and dose
Time frame: Up to 4 years 9 months
Change in Histone H3 Acetylation of Entinostat
Median (IQR) change in H3 acetylation in peripheral blood mononuclear cells (PBMCs) versus baseline stratified by study part, dose level.
Time frame: Up to 28 days
Change in Histone H4 Acetylation of Entinostat
Median (IQR) change in H4 acetylation in PBMCs versus baseline stratified by study part, dose level.
Time frame: Up to 28 days

Results

Posted Jan 31, 2023

Participant flow

Participant flow — Overall Study
Milestone	Stratum 1 With 3 mg/m²	Stratum 1 With 4 mg/m²	PK Part With 4 mg/m²
Started	6	9	6
Completed	0	0	0
Not completed	6	9	6
Withdrew: Death	1	0	0
Withdrew: Lack of efficacy	5	8	4
Withdrew: Physician decision	0	0	2
Withdrew: Withdrawal by subject	0	1	0

Outcome measures

PrimaryMaximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (R2PD) of Entinostat

The MTD/RP2D will be defined as the maximum dose at which fewer than one-third of patients experience dose limiting toxicity during cycle 1 of therapy among 6 toxicity-evaluable patients. The frequency of cycle 1 dose limiting toxicities will be summarized by dose level among patients in the dose escalation part of the study.

Time frame:: Up to 28 days
Reported as:: Number · mg/m²

Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (R2PD) of Entinostat
mg/m²	Treatment (Entinostat)
Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (R2PD) of Entinostat	4

PrimaryFrequency of Adverse Events for Entinostat

The frequency of patients with at least one Grade 3 or greater adverse event that are at least possibly attributable to entinostat during cycle 1 will be summarized by study part, dose level.

Time frame:: Up to 28 days
Reported as:: Count of participants · Participants

Frequency of Adverse Events for Entinostat
Participants	Stratum 1 With 3 mg/m²	Stratum 1 With 4 mg/m²	PK Part With 4 mg/m²
Frequency of Adverse Events for Entinostat	5	7	5

PrimaryHalf-life of Entinostat

The median (min, max) Half-Life of entinostat stratified by study part and dose level. The half-life (t1/2) was calculated using the equation t1/2 = 0.693/λz, where the terminal elimination rate constant (λz) was determined from a least-squares regression of the log-transformed plasma concentration vs. time data for the last 3 - 4 time points.

Time frame:: Plasma concentrations were measured at 0, 0.5, 1, 3, 6, 24, and 48-96 hours post-dose during cycle 1, day 1.
Reported as:: Median · Hours

Half-life of Entinostat
Hours	Stratum 1 With 3 mg/m²	Stratum 1 With 4 mg/m²	PK Part With 4 mg/m²
Half-life of Entinostat	50.96 (27.38 to 103.66)	46.04 (40.51 to 81.32)	44.23 (29.86 to 103.74)

PrimaryPeak Plasma Concentration of Entinostat: C-Max

The median (min, max) of the peak plasma concentration of entinostat stratified by study part, dose level. Time points were assessed at 0, 0.5, 1, 3, 6, 24, and 48-96 hours post-dose during cycle 1, day 1.

Time frame:: Up to 96 hours
Reported as:: Median · ng/ml

Peak Plasma Concentration of Entinostat: C-Max
ng/ml	Stratum 1 With 3 mg/m²	Stratum 1 With 4 mg/m²	PK Part With 4 mg/m²
Peak Plasma Concentration of Entinostat: C-Max	54.4 (5.19 to 136.00)	61.5 (14.00 to 107.00)	23.8 (19.10 to 293.00)

PrimaryTotal Area Under the Plasma Concentration Curve of Entinostat: AUC

The median (min, max) of the total area under the plasma concentration curve of entinostat stratified by study part, dose level. Time points were assessed at 0, 0.5, 1, 3, 6, 24, and 48-96 hours post-dose during cycle 1, day 1.

Time frame:: Up to 96 hours
Reported as:: Median · hr*ng/mL

Total Area Under the Plasma Concentration Curve of Entinostat: AUC
hr*ng/mL	Stratum 1 With 3 mg/m²	Stratum 1 With 4 mg/m²	PK Part With 4 mg/m²
Total Area Under the Plasma Concentration Curve of Entinostat: AUC	755 (252 to 1320)	1111 (816 to 1910)	1147 (1074 to 2349)

PrimaryTime to Reach Maximum Plasma Concentration of Entinostat: T-Max

The median (min, max) of the time to reach maximum plasma concentration of entinostat stratified by study part, dose level. Time points were assessed at 0, 0.5, 1, 3, 6, 24, and 48-96 hours post-dose during cycle 1, day 1.

Time frame:: Up to 96 hours
Reported as:: Median · Hours

Time to Reach Maximum Plasma Concentration of Entinostat: T-Max
Hours	Stratum 1 With 3 mg/m²	Stratum 1 With 4 mg/m²	PK Part With 4 mg/m²
Time to Reach Maximum Plasma Concentration of Entinostat: T-Max	1.01 (0.53 to 6.00)	0.59 (0.50 to 24.55)	1 (0.50 to 24.08)

SecondaryAntitumor Activity of Entinostat

Frequency of response to entinostat per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and/or assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR, stratified by study part and dose

Time frame:: Up to 4 years 9 months
Reported as:: Count of participants · Participants

Antitumor Activity of Entinostat
Participants	Stratum 1 With 3 mg/m²	Stratum 1 With 4 mg/m²	PK Part With 4 mg/m²
Antitumor Activity of Entinostat	0	0	0

SecondaryChange in Histone H3 Acetylation of Entinostat

Median (IQR) change in H3 acetylation in peripheral blood mononuclear cells (PBMCs) versus baseline stratified by study part, dose level.

Time frame:: Up to 28 days

No measurements were reported for this outcome.

SecondaryChange in Histone H4 Acetylation of Entinostat

Median (IQR) change in H4 acetylation in PBMCs versus baseline stratified by study part, dose level.

Time frame:: Up to 28 days

No measurements were reported for this outcome.

Adverse events

Collected over Up to 4 years 9 months. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Stratum 1 With 3 mg/m²	1/6 (16.7%)	5/6 (83.3%)	6/6 (100%)
Stratum 1 With 4 mg/m²	0/9 (0%)	7/9 (77.8%)	9/9 (100%)
PK Part With 4 mg/m²	2/6 (33.3%)	5/6 (83.3%)	6/6 (100%)

Most frequent serious events

Showing 10 of 62

Most frequent serious events
Event	Stratum 1 With 3 mg/m²	Stratum 1 With 4 mg/m²	PK Part With 4 mg/m²
HeadacheNervous system disorders	2/6	0/9	0/6
HypoxiaRespiratory, thoracic and mediastinal disorders	2/6	0/9	0/6
Lymphocyte count decreasedInvestigations	1/6	0/9	2/6
Neutrophil count decreasedInvestigations	1/6	3/9	1/6
HydrocephalusNervous system disorders	0/6	2/9	0/6
Abducens nerve disorderNervous system disorders	1/6	0/9	0/6
AcidosisMetabolism and nutrition disorders	1/6	0/9	0/6
AgitationPsychiatric disorders	1/6	0/9	0/6
Anal hemorrhageGastrointestinal disorders	0/6	0/9	1/6
AnemiaBlood and lymphatic system disorders	1/6	1/9	1/6

Most frequent other events

Showing 10 of 247

Most frequent other events
Event	Stratum 1 With 3 mg/m²	Stratum 1 With 4 mg/m²	PK Part With 4 mg/m²
Platelet count decreasedInvestigations	4/6	5/9	6/6
HeadacheNervous system disorders	5/6	4/9	3/6
VomitingGastrointestinal disorders	2/6	7/9	5/6
Aspartate aminotransferase increasedInvestigations	3/6	7/9	2/6
NauseaGastrointestinal disorders	4/6	7/9	4/6
Alanine aminotransferase increasedInvestigations	2/6	6/9	3/6
AnxietyPsychiatric disorders	4/6	4/9	1/6
FatigueGeneral disorders	3/6	6/9	1/6
HyperglycemiaMetabolism and nutrition disorders	2/6	6/9	4/6
HypermagnesemiaMetabolism and nutrition disorders	3/6	4/9	4/6

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)	Stratum 1 With 3 mg/m²	Stratum 1 With 4 mg/m²	PK Part With 4 mg/m²	Total
<=18 years	4	9	5	18
Between 18 and 65 years	2	0	1	3
>=65 years	0	0	0	0

Age, Continuous
Age, Continuous(years)	Stratum 1 With 3 mg/m²	Stratum 1 With 4 mg/m²	PK Part With 4 mg/m²	Total
Median	17.5 (13 to 20)	13 (8 to 17)	11 (6 to 19)	14 (6 to 20)

Sex: Female, Male
Sex: Female, Male(Participants)	Stratum 1 With 3 mg/m²	Stratum 1 With 4 mg/m²	PK Part With 4 mg/m²	Total
Female	2	5	4	11
Male	4	4	2	10

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Stratum 1 With 3 mg/m²	Stratum 1 With 4 mg/m²	PK Part With 4 mg/m²	Total
Hispanic or Latino	1	2	1	4
Not Hispanic or Latino	5	6	5	16
Unknown or Not Reported	0	1	0	1

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Stratum 1 With 3 mg/m²	Stratum 1 With 4 mg/m²	PK Part With 4 mg/m²	Total
American Indian or Alaska Native	0	0	0	0
Asian	0	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0	0
Black or African American	0	1	1	2
White	6	6	3	15
More than one race	0	2	2	4
Unknown or Not Reported	0	0	0	0

Study locations

21 sites

Children's Hospital of Alabama
Birmingham, Alabama 35233, United States
Children's Hospital Los Angeles
Los Angeles, California 90027, United States
Children's Hospital of Orange County
Orange, California 92868, United States
UCSF Medical Center-Mission Bay
San Francisco, California 94158, United States
Children's Hospital Colorado
Aurora, Colorado 80045, United States
Children's National Medical Center
Washington, District of Columbia 20010, United States
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia 30322, United States
Lurie Children's Hospital-Chicago
Chicago, Illinois 60611, United States
Riley Hospital for Children
Indianapolis, Indiana 46202, United States
Dana-Farber Cancer Institute
Boston, Massachusetts 02215, United States
C S Mott Children's Hospital
Ann Arbor, Michigan 48109, United States
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota 55455, United States
Washington University School of Medicine
Saint Louis, Missouri 63110, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York 10032, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio 45229, United States
Oregon Health and Science University
Portland, Oregon 97239, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania 19104, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania 15224, United States
Saint Jude Children's Research Hospital
Memphis, Tennessee 38105, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas 77030, United States
Seattle Children's Hospital
Seattle, Washington 98105, United States

References and documents

Study documents

Protocol and statistical analysis plan ↗ · Jan 31, 2019

PDFs hosted by the registry, ClinicalTrials.gov.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Oct 17, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02780804
Lead sponsor: National Cancer Institute (NCI)
Responsible party: Sponsor
First posted: May 24, 2016
Start date: Jan 6, 2017
Primary completion: Jun 30, 2021
Completion: Sep 30, 2021
Results posted: Jan 31, 2023
Last update: Oct 17, 2023

Study contacts

Andrew Bukowinski

principal investigator · COG Phase I Consortium

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Sep 2023. You cannot join it, but the record below documents what was studied.

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Discussion

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Studies of the drug tested here: Entinostat

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