MEKTOVI® for the Treatment of Pediatric Adamantinomatous Craniopharyngioma
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age1-39
SponsorNationwide Children's Hospital
About this trial
MEKTOVI (binimetinib) is an oral, highly selective reversible inhibitor of mitogen-activated extracellular signal regulated kinase 1 (MEK1) and MEK2. The biological activity of binimetinib that has been evaluated bith in vitro and in vivo in a wide variety of tumor types In this Phase II, the drug will be used to treat pediatric patients diagnosed with recurrent Adamantinomatous Craniopharyngioma including patients who have undergone surgery and/or radiation therapy.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age: Patients must be ≥ 12 months and ≤ 39 years of age at the time of study enrollment.
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.
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
Disqualifiers
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.
Patients with a history of serious gastrointestinal disease, including inflammatory bowel disease or gastrointestinal perforation
Patients who are unable to absorb enteral medications
Administration via NG/NJ/G-tube is allowed
Trial design
Design model
Single group
Treatments tested in this trial
Binimetinib Oral Tablet [Mektovi]
DrugBinimetinib oral continuous dosing 32 mg/m2 PO BID for 4 weeks
Treatment groups
38 Participants
are divided into 1 treatment groupGroup A: Stratum 1 and Stratum 2Experimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Sustained objective response rate of patients with recurrent/progressive previously irradiated ACP to treatment with oral binimetinib
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).
Time frame
From Day 1 of treatment through 30 days following end of protocol treatment2
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
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).
Time frame
From Day 1 of treatment through 30 days following end of protocol treatmentSecondary outcomes
1
Biological effects of binimetinib on ACP tumor tissue and cyst fluid.
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.
Time frame
From Day 1 of treatment through 30 days following end of protocol treatment2
Toxicities associated with tocilizumab in children with ACP
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
Time frame
24 months3
PFS of ACP patients treated with binimetinib after radiation
To assess one-year progression-free survival (PFS) rates for patients with ACP who are treated with binimetinib following progression after radiation (Stratum 1).
Time frame
12 months4
PFS of ACP patients treated with binimetinib who have not received radiation
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).
Time frame
12 monthsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Nationwide Children's Hospital
Lead sponsor
Children's Hospital Colorado
Collaborator
Source ClinicalTrials.gov