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JOURNAL ONKOLOGIE – STUDIE

MEKTOVI® for the Treatment of Pediatric Adamantinomatous Craniopharyngioma

Rekrutierend

NCT-Nummer:
NCT05286788

Studienbeginn:
April 2023

Letztes Update:
08.08.2024

Wirkstoff:
Binimetinib Oral Tablet [Mektovi]

Indikation (Clinical Trials):
Craniopharyngioma, Adamantinoma

Geschlecht:
Alle

Altersgruppe:
Alle

Phase:
Phase 2

Sponsor:
Nationwide Children's Hospital

Collaborator:
Children's Hospital Colorado

Studienleiter

Kathleen H Dorris
Study Chair
Children's Hospital Colorado
Todd C Hankinson
Study Chair
Children's Hospital Colorado
Maryam Fouladi
Principal Investigator
Nationwide Children's Hospital

Kontakt

Studienlocations
(3 von 17)

Hopp Children's Cancer Center at NCT Heidelberg (KiTZ)
69120 Heidelberg
(Baden-Württemberg)
GermanyNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Olaf Witt, MD
Phone: 49 6221 42 3570
E-Mail: o.witt@kitz-heidelberg.de» Ansprechpartner anzeigen
Ann & Robert H. Lurie Children's Hospital of Chicago
60611 Chicago
United StatesNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Ashley Plant, MD
Phone: 312-227-4090
E-Mail: Aplant@luriechildrens.org» Ansprechpartner anzeigen
Montreal Children's Hospital
H4A3J1 Montréal
CanadaNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Genevieve Legault, MD
Phone: 514-412-4400
Phone (ext.): 60497
E-Mail: Genevieve.legault4@mcgill.ca» Ansprechpartner anzeigen
Princess Máxima Center
3720 Utrecht
NetherlandsNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Jasper van der Lugt, MD, PhD
Phone: +31618559694
E-Mail: J.vanderLugt@prinsesmaximacentrum.nl» Ansprechpartner anzeigen
Alle anzeigen

Studien-Informationen

Detailed Description:

Adamantinomatous Craniopharyngioma (ACP) is a highly debilitating pediatric brain tumor

that lacks medical anti-tumor therapies. Current therapy, which depends largely on

surgery and radiation, is associated with poor quality of life and becomes more

challenging and risky in the setting of recurrent disease. Recent discoveries regarding

the biological characteristics of ACP indicate that available agents, including

Mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway

inhibitors may have efficacy in the control of ACP. Binimetinib is one such agent.

In this study, up to 38 patients will receive oral binimetinib at the recommended phase 2

pediatric dose (RP2D) of 32 mg/m2/dose PO every 12 hours for 4 weeks which represents one

cycle. Cycles will last 28 days and treatment may continue for up to two years (26

cycles).

It will be a multi-center Phase 2 trial with two strata for patients aged >1 year and <25

years with measurable ACP who may have been previously treated with radiation (Stratum 1,

18 patients) or without radiation (Stratum 2, 18 patients).

Ein-/Ausschlusskriterien

Inclusion Criteria:

1. Age: Patients must be ≥ 12 months and ≤ 25 years of age at the time of study

enrollment.

2. Diagnosis: Patients with histologically-confirmed adamantinomatous craniopharyngioma

(ACP) Histologic confirmation of ACP may be made on solid tumor or, if no solid

tumor can be safely obtained, cyst fluid with classic ACP characteristics of thick,

cholesterol-rich, greenish-brown liquid in the context of imaging features

consistent with craniopharyngioma, including lobulated, cystic/solid mass with

calcifications that originates in the sellar/suprasellar region.

3. Disease Status: Patients must have measurable disease.

- Stratum 1: Patients with progressive or recurrent ACP who demonstrate cystic

and/or solid recurrence or progression at least 6 months post completion of

radiation therapy

- Stratum 2: Patients with measurable ACP who have undergone surgery but have NOT

previously undergone irradiation (but may have received prior systemic or

intracystic therapy). Progressive disease is allowed but not required.

4. Performance Level: Karnofsky ≥ 50% for patients > 16 years of age and Lansky ≥ 50

for patients ≤ 16 years of age (See Appendix I). Note: Neurologic deficits in

patients with CNS tumors must have been 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.

5. Prior Therapy: Patients must have recovered or stabilized from the acute toxic

effects of prior treatments

- Biologic (anti-neoplastic agent): At least 7 days must have elapsed after the

last (systemic or intracystic) dose of a biologic agent. 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

- Immunotherapy: At least 42 days after the completion of any type of systemic

immunotherapy, e.g. tumor vaccines.

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

antibody.

- Radiation therapy: Patients must have had their last (conventional or

hypofractionated) fraction of: a) Focal irradiation > 6 months prior to

enrollment and b) No prior craniospinal irradiation is permitted.

- Corticosteroids: Patients receiving dexamethasone must be on a stable or

decreasing dose for at least 1 week prior to enrollment

- Myelosuppressive systemic therapy: At least 21 days must have elapsed after the

last systemic myelosuppressive therapy.

- Surgery: At least 6 weeks must have elapsed since surgery.

6. Organ Function Requirements

Adequate Bone Marrow Function Defined as:

- Peripheral absolute neutrophil count (ANC) ≥1000/mm3

- Platelet count ≥100,000/mm3 (transfusion independent, defined as not receiving

platelet transfusions for at least 7 days prior to enrollment)

- Hemoglobin >8 g/dL (may be transfused)

Adequate Renal Function Defined as:

- Creatinine clearance or radioisotope GFR > 70ml/min/1.73 m2 or

- A serum creatinine based on (Schwartz et al. J. Peds, 106:522, 1985) age/gender

as follows:

1. to < 2 years: maximum serum creatinine 0.6 mg/dL for males and females. 2

to < 6 years: maximum serum creatinine 0.8 mg/dL for males and females. 6

to < 10 years: maximum serum creatinine 1.0 mg/dL for males and females.

10 to < 13 years: maximum serum creatinine 1.2 mg/dL for males and

females. 13 to < 16 years: maximum serum creatinine 1.5 mg/dL for males

and 1.4 mg/dL for females. ≥ 16 years: maximum serum creatinine 1.7 mg/dL

for males and 1.4 mg/dL for females.

Adequate Liver Function Defined as:

- Total bilirubin ≤ 1.5 × institutional upper limit of normal

- AST (SGOT) ≤ 2.5 × institutional upper limit of normal

- ALT (SGPT) ≤ 2.5 × institutional upper limit of normal

Adequate Cardiac Function Defined as:

- Left Ventricular Ejection Fraction greater than the institutional lower limit

of normal by echocardiogram

- QTc ≤ 480 msec (by Bazett formula)

Adequate Neurologic Function Defined as:

- Patients with neurological deficits should have deficits that are stable for a

minimum of 1 week prior to enrollment.

- Patients with current seizure disorders may be enrolled if seizures are

well-controlled on antiepileptic therapies.

7. Informed Consent: 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:

1. Pregnancy or Breast-Feeding: Pregnant or breast-feeding women will not be entered on

this study due to unknown risks of fetal and teratogenic adverse events as seen in

animal/human studies. 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 for at least 90

days after discontinuation of drug for females and at least 60 days for males. For

females of childbearing potential, agreement to remain abstinent (refrain from

heterosexual intercourse) or use contraceptive methods (bilateral tubal ligation,

male sterilization, hormonal contraceptives that inhibit ovulation,

hormone-releasing intrauterine devices, and copper intrauterine devices; hormonal

contraceptive methods must be supplemented by a barrier method) and agreement to

refrain from donating eggs are required. For males of reproductive potential,

agreement to remain abstinent (refrain from heterosexual intercourse) or use a

condom, and agreement to refrain from donating sperm.

2. Gastrointestinal Disease:

- Patients with a history of serious gastrointestinal disease, including

inflammatory bowel disease or gastrointestinal perforation

- Patients who are unable to swallow, retain or absorb oral medications

3. Concomitant Medications

- Corticosteroids: 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.

- Investigational Drugs: Patients who are currently receiving another

investigational drug are not eligible.

- Anti-cancer Agents: Patients who are currently receiving other anti-cancer

agents are not eligible.

4. Study Specific:

- Patients who have an uncontrolled infection are not eligible.

- Patients who have received any live or attenuated vaccinations within three

months prior to start of therapy are not eligible.

- Any significant concurrent medical or surgical condition that would jeopardize

the patient's safety or ability to complete the study, including, but not

limited to, disease of the nervous, renal, hepatic, cardiac (such as

symptomatic congestive heart failure, unstable angina pectoris, cardiac

arrhythmia), pulmonary, or endocrine system

- Patients who have a history of Human Immunodeficiency Virus, Hepatitis B Virus,

Hepatitis C Virus or Tuberculosis 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 who have a history of alcohol, drug, or chemical abuse within 6 months

of screening.

- Patients who have had surgery within the last 6 weeks or who have concerns for

poor postsurgical wound healing.

- Patients who have a history of allergic reactions attributed to compounds of

similar chemical or biologic composition to tocilizumab and its excipients are

not eligible.

Studien-Rationale

Primary outcome:

1. Sustained objective response rate of patients with recurrent/progressive previously irradiated ACP to treatment with oral binimetinib (Time Frame - From Day 1 of treatment through 30 days following end of protocol treatment):
To calculate the number of patients who experience sustained objective response rate [minor response (MR) + partial response (PR) + complete response (CR)] of patients with recurrent/progressive previously irradiated Adamantinomatous Craniopharyngioma to treatment with oral binimetinib (Stratum 1).

2. Sustained objective response rate of patients with measurable ACP who have undergone surgery but have not been previously treated with radiation to treatment with oral binimetinib (Time Frame - From Day 1 of treatment through 30 days following end of protocol treatment):
To calculate the number of patients who experience sustained objective response rate (MR + PR + CR) of patients with measurable Adamantinomatous Craniopharyngioma who have undergone surgery but have not been previously treated with radiation to treatment with oral binimetinib (Stratum 2).

Secondary outcome:

1. Biological effects of binimetinib on ACP tumor tissue and cyst fluid. (Time Frame - From Day 1 of treatment through 30 days following end of protocol treatment):
To measure concentrations of various chemokines including IL-6, IL-8, IL-10 and CXCL1in cyst fluid or tumor or blood of ACP patients treated with binimetinib. Comparisons will be made with known levels in the literature and among patient samples from within the study.

2. Toxicities associated with tocilizumab in children with ACP (Time Frame - 24 months):
To calculate the number of participants with, as well as frequency and severity of, binimetinib-related Adverse Events as assessed by CTCAE v5.0 in children with recurrent or refractory ACP

3. PFS of ACP patients treated with binimetinib after radiation (Time Frame - 12 months):
To assess one-year progression-free survival (PFS) rates for patients with ACP who are treated with binimetinib following progression after radiation (Stratum 1).

4. PFS of ACP patients treated with binimetinib who have not received radiation (Time Frame - 12 months):
To assess one-year progression-free survival (PFS) rates for patients with ACP who are treated with binimetinib who have not previously received radiation (Stratum 2).

Geprüfte Regime

  • Binimetinib Oral Tablet [Mektovi] (MEKTOVI):
    Binimetinib oral continuous dosing 32 mg/m2 PO BID for 4 weeks

Quelle: ClinicalTrials.gov


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