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JOURNAL ONKOLOGIE – STUDIE
PNOC016

Fimepinostat in Treating Brain Tumors in Children and Young Adults

Rekrutierend

NCT-Nummer:
NCT03893487

Studienbeginn:
August 2019

Letztes Update:
21.04.2021

Wirkstoff:
Fimepinostat

Indikation (Clinical Trials):
Glioblastoma, Glioma, Astrocytoma, Medulloblastoma

Geschlecht:
Alle

Altersgruppe:
Alle

Phase:
Frühphase (Phase 0)

Sponsor:
Sabine Mueller, MD, PhD

Collaborator:
Pacific Pediatric Neuro-Oncology Consortium, Cannonball Kids' Cancer Foundation, Curis, Inc.,

Studienleiter

Sabine Mueller, MD, PhD
Principal Investigator
University of California, San Francisco

Kontakt

Studienlocations
(3 von 16)

University of California, San Francisco
94143 San Francisco
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Kelly Hitchner
Phone: 415-502-1600
E-Mail: PNOC_Regulatory@ucsf.edu

Sabine Mueller, MD, PhD
Phone: 877-827-3222
E-Mail: cancertrials@ucsf.edu
» Ansprechpartner anzeigen
Children's National Medical Center
20010 Washington
United StatesRekrutierend» Google-Maps
University of Florida
32611 Gainesville
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Sridharan Gururangan, FRCP
Phone: 352-294-8347
E-Mail: Sridharan.Gururangan@neurosurgery.ufl.edu
» Ansprechpartner anzeigen
University of Michigan Hospital
48109 Ann Arbor
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Andrea Franson, MD, MS
E-Mail: atflynn@med.umich.edu

Carl Koschmann, MD
E-Mail: ckoschma@med.umich.edu
» Ansprechpartner anzeigen
Children's Minnesota Research Institute
55404 Minneapolis
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Anne Bendel, MD
Phone: 612-813-5940
E-Mail: anne.bendel@childrensmn.org

Maggie Skrypek, MD
Phone: 612-813-5940
E-Mail: maggie.skrypek@childrensmn.org
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Children's Hospital of Philadelphia (CHOP)
19146 Philadelphia
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Cassie Kline, MD, MAS
E-Mail: KLINEC@EMAIL.CHOP.EDU

Jane Minturn, MD, PhD
Phone: 267-4265026
E-Mail: MINTURN@email.chop.edu
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St. Jude Children's Research Hospital
38105 Memphis
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Amar Gajjar, MD
Phone: 901-595-2615
E-Mail: Amar.Gajjar@STJUDE.ORG

Christopher Tinkle, MD
Phone: 901-595-8735
E-Mail: Christopher.Tinkle@STJUDE.ORG
» Ansprechpartner anzeigen
Texas Children's Hospital
77030 Houston
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Holly Lindsay, MD
Phone: 832-824-2146
E-Mail: hblindsa@txch.org

Patricia Baxter, MD
E-Mail: pabaxter@txch.org
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University of Utah, Children's Primary
84113 Salt Lake City
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Nicholas Whipple, MD, MPH
Phone: 801-662-4700
E-Mail: Nicholas.whipple@hsc.utah.edu
» Ansprechpartner anzeigen
The University Children's Hospital in Zurich
8032 Zürich
SwitzerlandRekrutierend» Google-Maps
Ansprechpartner:
Nicolas Gerber, MD
Phone: +41 44 266 31 17

Stephanie Mathes, PhD
Phone: +41 44 266 3726
E-Mail: PNOC_regulatory@ucsf.edu
» Ansprechpartner anzeigen
Alle anzeigen

Studien-Informationen

Detailed Description:

PRIMARY OBJECTIVES:

I. To confirm penetration of fimepinostat across the blood brain barrier (BBB) in children

and young adults with newly diagnosed diffuse intrinsic pontine glioma (DIPG), recurrent

medulloblastoma, or recurrent high-grade glioma (HGG) by measuring concentration of

fimepinostat and metabolite in primary tumor tissue.

EXPLORATORY OBJECTIVES:

I. To assess pharmacokinetics (PK) of fimepinostat in plasma and tumor tissue of children and

young adults with newly diagnosed DIPG, recurrent medulloblastoma, or recurrent HGG.

II. To assess pharmacodynamics (PD) of fimepinostat in children and young adults with newly

diagnosed DIPG, recurrent medulloblastoma, or recurrent HGG as measured by phosphorylation

and acetylation in tumor tissue.

III. To correlate acetylation and phosphorylation in tumor tissue with tissue and plasma PK

levels.

IV. To assess the safety and tolerability of fimepinostat in children and young adults with

newly diagnosed DIPG, recurrent medulloblastoma, or recurrent HGG.

V. To assess preliminary efficacy of fimepinostat given as monotherapy after surgery in

children and young adults with newly diagnosed DIPG, recurrent medulloblastoma, or recurrent

HGG, as based on progression-free survival (PFS) and objective response rate (ORR) as

appropriate.

OUTLINE:

Patients receive fimepinostat orally (PO) once daily (QD) on days -2 to 0. Within 2 hours of

receiving fimepinostat on day 0, patients undergo tumor resection.

MAINTENANCE PHASE: Patients receive fimepinostat by mouth, once daily for days 1-5 each week.

Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity

for up to 12 months from the time treatment begins. Should patients continue to derive

clinical benefit, and not experience excess toxicity or progression, patients can continue to

receive drug for up to 24 months or longer pending discussion with study chairs and study

sponsor.

After completion of study treatment, patients are followed up at 30 days, then every 3 months

for up to 5 years.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Patients must have one of the following histologically confirmed diagnoses (histologic

confirmation from initial diagnosis acceptable, as appropriate):

- Stratum A: Newly diagnosed diffuse intrinsic pontine glioma (WHO grade II-IV) -

this stratum does not require tissue confirmation at time of enrollment, but

diagnostic confirmation will be required to continue on study after biopsy.

Patients with newly diagnosed DIPG will be eligible to enroll before or after

standard of care radiation, but must be eligible for a biopsy. Newly diagnosed

DIPG stratum should not have received prior therapy before the initiation of

fimepinostat, with the exception of those patients who received temozolomide

during radiation therapy or who previously received radiation as per standard of

care and have not yet undergone a biopsy. All patients who have received therapy

other than radiation and temozolomide should be discussed with study chair(s)

prior to enrollment. Patients enrolling after standard of care radiation must be

enrolled within 14 weeks of completion of radiotherapy.

- Stratum B: Recurrent medulloblastoma (WHO grade IV), any molecular subtype

- Stratum C: Recurrent high-grade glioma (HGG), including anaplastic astrocytoma

(WHO grade III) and glioblastoma (WHO grade IV)

- Stratum B & C: Patients in the recurrent medulloblastoma or recurrent HGG

arm can have locally recurrent or disseminated disease, provided

resection/biopsy would still be clinically indicated. Disseminated disease

can be diagnosed by imaging or Cerebrospinal fluid (CSF) cytology. Recurrent

DIPG will be eligible for stratum C; however, eligibility requires

biopsy/resection is feasible in a region of tumor outside of the pons (i.e.

cerebellar extension or new metastatic site). These patients should be

discussed with study chair(s) prior to enrollment

- Patients must be able to swallow intact fimepinostat capsules or mini-tabs without

chewing or crushing

- Patients must have body surface area (BSA) >= 0.5 m^2

- Patients must undergo tumor tissue collection as part of their standard of care

- Minimum possible tissue collected must be equivalent to about 4-6 stereotactic

core biopsies

- Prior Therapy: Patients in the medulloblastoma and HGG strata will be allowed to have

undergone prior therapy including surgery, chemotherapy, and radiation therapy.

Patients in the newly diagnosed DIPG stratum should not have received prior therapy

before the initiation of fimepinostat, with the exception of those patients who

received temozolomide during radiation therapy or who previously received radiation as

per standard of care and have not yet undergone a biopsy. All patients who have

received therapy other than radiation and temozolomide should be discussed with study

chair(s) prior to enrollment. Patients must have fully recovered from acute side

effects related to previous anti-cancer therapies. Patients undergoing radiation

during protocol therapy will not be permitted to receive other concomitant agents with

radiation and pending initiation of maintenance with fimepinostat

- Myelosuppressive chemotherapy: At least 21 days after last dose of

myelosuppressive chemotherapy (42 days if prior nitrosourea)

- Hematopoietic growth factors: At least 14 days after last dose of a long-acting

growth factor or 7 days after short-acting growth factor or beyond time during

which adverse events are known to occur

- Biologic (anti-neoplastic agent): At least 7 days after last dose of a biologic

agent or beyond time during which adverse events are known to occur

- Monoclonal antibodies: At least 21 days after last dose of monoclonal antibody

- Radiotherapy:

- At least 2 weeks after local palliative radiotherapy (XRT)

- At least 3 months from craniospinal XRT, or XRT to > 50% pelvis

- Surgery:

- At least 21 days from major surgery (biopsy and central line

placement/removal are not considered major)

- Corticosteroids: Subjects who are receiving dexamethasone must be on a stable or

decreasing dose for at least 7 days prior to enrollment

- Peripheral absolute neutrophil count (ANC) >= 1000/mm^3

- Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving

platelet transfusions for at least 7 days prior to enrollment)

- Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70

milliliters (mL)/minute (min)/1.73 m^2 or

- A serum creatinine based on age/gender as follows:

- Age: Maximum Serum Creatinine (mg/dL)

- 3 to < 6 years: 0.8 (male), 0.8 (female)

- 6 to < 10 years: 1 (male), 1 (female)

- 10 to < 13 years: 1.2 (male), 1.2 (female)

- 13 to < 16 years: 1.5 (male), 1.4 (female)

- >= 16 years: 1.7 (male), 1.4 (female)

- Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for

age

- Serum glutamate pyruvate transaminase (SGPT)/alanine aminotransferase (ALT) =< 110 U/L

- Serum albumin >= 2 g/dL

- Neurologic function:

- Subjects with seizure disorder may be enrolled if well controlled

- Gastrointestinal function:

- Diarrhea < grade 2 by Common Terminology Criteria for Adverse Events (CTCAE)

version (v)5.0

- Metabolic function:

- Non-fasting glucose < 125 mg/dL without the use of antihyperglycemic agents

- If non-fasting glucose > 125 mg/dL, a fasting glucose should be done. If

fasting glucose =< 160 mg/dL without the use of antihyperglycemic agents,

patient will meet adequate metabolic function criteria

- Cardiac function: corrected QT (QTc) < 480 msec

- The effects of fimepinostat on the developing human fetus are unknown. For this

reason, women of child-bearing potential and men must agree to use adequate

contraception (hormonal or barrier method of birth control; abstinence) prior to study

entry, for the duration of study participation and 30 days after completion of

fimepinostat administration. Should a woman become pregnant or suspect she is pregnant

while she or her partner is participating in this study, she should inform her

treating physician immediately

- A legal parent/guardian or patient must be able to understand, and willing to sign, a

written informed consent and assent document, as appropriate

Exclusion Criteria:

- Subjects who have not recovered from acute adverse events due to therapeutic agents

administered more than 4 weeks earlier

- Patients must not have received prior therapy with single-agent or combination histone

deacetylase (HDAC) and Phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)

inhibitors

- Subjects who are receiving any other investigational agent

- History of allergic reaction to compounds of similar chemical or biological

composition to fimepinostat

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active

infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac

arrhythmia, or psychiatric illness/social situation that would limit compliance with

study requirements

- Patients with active human immunodeficiency virus (HIV) infection and with potential

life-threatening consequences associated with immune-suppressive therapy

- Patients with history of type 1 or 2 diabetes mellitus

- Patients with gastrointestinal condition that could interfere with absorption or

metabolism of fimepinostat

Studien-Rationale

Primary outcome:

1. Penetration of fimepinostat across the blood brain barrier (BBB) (Time Frame - During surgery or biopsy):
Will be analyzed using descriptive statistics from results of fimepinostat concentrations measured within the tumor tissue collected at the time of a standard of care surgery or biopsy. Within each strata, Simon's two-stage design will be used.

Geprüfte Regime

  • Fimepinostat (CUDC-907):
    Fimepinostat capsules
  • Therapeutic Conventional Surgery:
    Undergo surgery

Quelle: ClinicalTrials.gov


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