Entinostat in Treating Pediatric Patients With Recurrent or Refractory Solid Tumors



Status:Recruiting
Conditions:Brain Cancer, Brain Cancer, Lymphoma
Therapuetic Areas:Oncology
Healthy:No
Age Range:Any - 21
Updated:3/20/2019
Start Date:December 26, 2016

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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

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.

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.

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 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

- 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 graft versus
host disease (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)

- Hemoglobin >= 8.0 g/dl, with or without transfusion (within 7 days prior to
enrollment)

- Patients with known bone marrow metastatic disease will not be eligible

- Creatinine clearance or radioisotope glomerular filtration rate (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)

- Bilirubin (sum of conjugated + conjugated) =< 1.5 x upper limit of normal (ULN) for
age (within 7 days prior to enrollment)

- Serum glutamate pyruvate transaminase (SGPT) (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 informed consent; assent, when appropriate, will be obtained according to
institutional guidelines

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 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
We found this trial at
21
sites
4401 Penn Avenue
Pittsburgh, Pennsylvania 15224
412-692-5325
Principal Investigator: Jean M. Tersak
Phone: 888-823-5923
Children's Hospital of Pittsburgh of UPMC UPMC is one of the leading nonprofit health systems...
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1600 7th Avenue
Birmingham, Alabama 35233
(205) 638-9100
Principal Investigator: Gregory K. Friedman
Phone: 888-823-5923
Children's Hospital of Alabama Children
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3333 Burnet Avenue # Mlc3008
Cincinnati, Ohio 45229
 1-513-636-4200 
Principal Investigator: James I. Geller
Phone: 888-823-5923
Cincinnati Children's Hospital Medical Center Patients and families from across the region and around the...
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4650 Sunset Blvd
Los Angeles, California 90027
 (323) 660-2450
Principal Investigator: Leo Mascarenhas
Phone: 888-823-5923
Childrens Hospital Los Angeles Children's Hospital Los Angeles is a 501(c)(3) nonprofit hospital for pediatric...
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262 Danny Thomas Pl
Memphis, Tennessee 38105
(901) 495-3300
Principal Investigator: Wayne L. Furman
Phone: 888-823-5923
St. Jude Children's Research Hospital St. Jude is unlike any other pediatric treatment and research...
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1201 W La Veta Ave
Orange, California 92868
(714) 997-3000
Principal Investigator: Josephine H. Haduong
Phone: 888-823-5923
Children's Hospital of Orange County For more than 45 years, CHOC Children’s has been steadfastly...
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Orange, CA
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South 34th Street
Philadelphia, Pennsylvania 19104
 215-590-1000
Principal Investigator: Elizabeth Fox
Phone: 888-823-5923
Children's Hospital of Philadelphia Since its start in 1855 as the nation's first hospital devoted...
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3181 Southwest Sam Jackson Park Road
Portland, Oregon 97239
503 494-8311
Principal Investigator: Suman Malempati
Phone: 503-494-1080
Oregon Health and Science University In 1887, the inaugural class of the University of Oregon...
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1540 East Hospital Drive
Ann Arbor, Michigan 48109
(877) 475-6688
Principal Investigator: Rajen Mody
Phone: 888-823-5923
C S Mott Children's Hospital Behind the doors of C.S. Mott Children's Hospital there exist...
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Atlanta, Georgia 30322
Principal Investigator: William T. Cash
Phone: 888-823-5923
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13123 E 16th Ave
Aurora, Colorado 80045
(720) 777-1234
Principal Investigator: Margaret E. Macy
Phone: 888-823-5923
Children's Hospital Colorado At Children's Hospital Colorado, we see more, treat more and heal more...
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450 Brookline Ave
Boston, Massachusetts 2215
617-632-3000
Principal Investigator: Steven G. DuBois
Phone: 877-442-3324
Dana-Farber Cancer Institute Since it’s founding in 1947, Dana-Farber has been committed to providing adults...
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Chicago, Illinois 60614
Principal Investigator: Stewart Goldman
Phone: 888-823-5923
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Houston, Texas 77030
Principal Investigator: Jodi Muscal
Phone: 713-798-1354
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705 Riley Hospital Dr
Indianapolis, Indiana 46202
(317) 944-5000
Principal Investigator: James M. Croop
Phone: 800-248-1199
Riley Hospital for Children Riley Hospital for Children at IU Health is a place of...
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Minneapolis, Minnesota 55455
Principal Investigator: Emily G. Greengard
Phone: 888-823-5923
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New York, New York 10032
Principal Investigator: Alice Lee
Phone: 212-305-6361
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660 S Euclid Ave
Saint Louis, Missouri 63110
(314) 362-5000
Principal Investigator: Robert J. Hayashi
Phone: 800-600-3606
Washington University School of Medicine Washington University Physicians is the clinical practice of the School...
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San Francisco, California 94158
Principal Investigator: Kieuhoa T. Vo
Phone: 877-827-3222
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4800 Sand Point Way NE
Seattle, Washington 98105
(206) 987-2000
Principal Investigator: Julie R. Park
Phone: 888-823-5923
Seattle Children's Hospital Seattle Children’s Hospital specializes in meeting the unique physical, emotional and developmental...
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111 Michigan Ave NW
Washington, District of Columbia
(202) 476-5000
Principal Investigator: AeRang Kim
Phone: 888-823-5923
Childrens National Medical Center As the nation’s children’s hospital, the mission of Children’s National Medical...
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