Entinostat in Treating Pediatric Patients With Recurrent or Refractory Solid Tumors
A Phase 1 Study of Entinostat, an Oral Histone Deacetylase Inhibitor, in Pediatric Patients With Recurrent or Refractory Solid Tumors, Including CNS Tumors and Lymphoma
3 other identifiers
interventional
21
1 country
21
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Jan 2017
Longer than P75 for phase_1
21 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 23, 2016
CompletedFirst Posted
Study publicly available on registry
May 24, 2016
CompletedStudy Start
First participant enrolled
January 6, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 30, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
September 30, 2021
CompletedResults Posted
Study results publicly available
January 31, 2023
CompletedOctober 17, 2023
September 1, 2023
4.5 years
May 23, 2016
October 3, 2022
September 22, 2023
Conditions
Outcome Measures
Primary Outcomes (6)
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.
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.
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.
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.
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.
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.
Up to 96 hours
Secondary Outcomes (3)
Antitumor Activity of Entinostat
Up to 4 years 9 months
Change in Histone H3 Acetylation of Entinostat
Up to 28 days
Change in Histone H4 Acetylation of Entinostat
Up to 28 days
Study Arms (1)
Treatment (entinostat)
EXPERIMENTALPatients 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.
Interventions
Eligibility Criteria
You may qualify if:
- 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 refractory solid tumors, including central nervous system (CNS) tumors or lymphoma, are eligible; patients must have had histologic verification of malignancy 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
- Karnofsky \>= 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. corticosteroid, 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 platelet or absolute neutrophil count \[ANC\] 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
- +23 more criteria
You may not qualify if:
- 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 reproductive potential may not participate unless they have agreed to use an effective contraceptive 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 corticosteroids 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 investigational 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 graft-versus-host disease 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 corrected QT (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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (21)
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 D.C., 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
St 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
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Results Reporting Coordinator
- Organization
- Children's Oncology Group
Study Officials
- PRINCIPAL INVESTIGATOR
Andrew Bukowinski
COG Phase I Consortium
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 23, 2016
First Posted
May 24, 2016
Study Start
January 6, 2017
Primary Completion
June 30, 2021
Study Completion
September 30, 2021
Last Updated
October 17, 2023
Results First Posted
January 31, 2023
Record last verified: 2023-09