MEKTOVI® for the Treatment of Pediatric Adamantinomatous Craniopharyngioma

• Drug: Binimetinib Oral Tablet [Mektovi]

Inclusion Criteria:

1. Age: Patients must be ≥ 12 months and ≤ 25 years of age at the time of study enrollment.
2. Diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results: 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 imagingtests that create detailed images of areas inside the body features consistent with craniopharyngioma, including lobulated, cystic/solid massa growth of cells that come together to make a lump, may or may not be cancer 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 recurrenceto occur or happen again 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 ambulatoryable to walk or move around unassisted for the purpose of assessing the performance score.
5. Prior Therapy: Patients must have recovered or stabilized from the acutenew, recent, comes with an urgent or significant sense, is sudden, sharp toxic effects of prior treatments
   • Biologic (anti-neoplastic agent): At least 7 days must have elapsed after the last (systemic or intracystic) dosethe amount of medication taken 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
   • Immunotherapya treatment that uses a person's immune system to fight cancer: 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 antibodya protein made by the immune system to fight against harmful substances (antigens), such as bacteria or viruses.
   • 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.
   • Corticosteroidsa type of anti-inflammatory medication that is used to treat inflammation: 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 major or intermediate surgery. Major surgery includes major craniotomya surgical procedure involving the temporary removal of a portion of the skull to access the brain for tumor resectionsurgical removal of tissue or part/all of an organ of cyst fenestration, organ resection, and exploratory laparotomy. Intermediate procedures include ventriculoperitoneal shunt placement, stereotactic brain biopsyremoval of a section of tissue to analyse for cancer cells, and intraventricular cathetera hollow tube put into the body to help drain fluids such as urine from the bladder or inject fluids such as long term antibiotics placement. Minor procedures that are not excluded include skin biopsy/incision and drainage, bone marrowsoft, spongy tissue found in bones that makes blood cells aspirateto draw out fluid or tissue from the body, often with a syringe, and central venous catheter placement, ommaya aspirations, lumbar punctures, and nasal endoscopya procedure that involves inserting a long, flexible tube with a light and small camera (endoscope) into the body to view internal organs to remove packing.
6. Organ Function RequirementsAdequate 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 echocardiograma type of ultrasound that uses sound waves to create detailed images of the heart to assess heart structure, function and blood flow
   • 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 Consenta process in which a patient receives detailed information about a procedure or treatment, including its potential risks, benefits, and alternatives. The patient then has the opportunity to understand the information and voluntarily agree to the procedure or treatment.: 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.