Selinexor in Treating Younger Patients With Recurrent or Refractory Solid Tumors or High-Grade Gliomas

Inclusion Criteria:

• Patients must have a body surface area (BSA) >= 0.84 m^2

• Diagnosis:

• Part A: Patients with recurrent or refractory solid tumors, including lymphomaand CNS tumors, are eligible; patients must have had histologic verification ofmalignancy at original diagnosis or relapse except in patients with intrinsicbrain stem tumors, optic pathway gliomas, or patients with pineal tumors andelevations of cerebrospinal fluid (CSF) or serum tumor markers includingalpha-fetoprotein or beta-human chorionic gonadotropin (HCG)

• Part B: Patients with recurrent or refractory high grade glioma (World HealthOrganization [WHO] grade III/IV) including disseminated tumors (excludingdiffuse intrinsic pontine glioma [DIPG]), not requiring surgical resection;patients must have had histologic verification of malignancy at originaldiagnosis or relapse

• Part C: Patients with recurrent or refractory high grade glioma (WHO gradeIII/IV) and requiring surgical resection (excluding DIPG and disseminatedtumors), who in the opinion of treating physicians, are medically stable toreceive 2 doses of selinexor (8-10 days of treatment) before undergoing surgerywithout compromising the success of the procedure; note that if, in the opinionof treating physicians, current symptoms necessitate surgery before 2 doseswill be able to be received, surgery should not be delayed to administerselinexor, and the patient would be ineligible for protocol therapy

• Disease status:

• Part A: Patients must have either measurable or evaluable disease

• Parts B and C: Patients must have measurable disease on imaging

• Patient's current disease state must be one for which there is no known curativetherapy 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 =< 16years of age; Note: Neurologic deficits in patients with CNS tumors must have beenrelatively stable for at least 7 days prior to study enrollment; patients who areunable to walk because of paralysis, but who are up in a wheelchair, will beconsidered ambulatory for the purpose of assessing the performance score

• Patients must have fully recovered from the acute toxic effects of all prioranti-cancer therapy and must meet the following minimum duration from prioranti-cancer directed therapy prior to enrollment; if after the required timeframe,the numerical eligibility criteria are met, e.g. blood count criteria, the patientis considered to have recovered adequately

• Myelosuppressive chemotherapy: At least 21 days after the last dose ofmyelosuppressive chemotherapy (42 days if prior nitrosourea)

• Hematopoietic growth factors: At least 14 days after the last dose of along-acting growth factor (e.g. Neulasta) or 7 days for short-acting growthfactor; for agents that have known adverse events occurring beyond 7 days afteradministration, this period must be extended beyond the time during whichadverse events are known to occur; the duration of this interval must bediscussed with the study chair

• Biologic (anti-neoplastic agent): At least 7 days after the last dose of abiologic agent; for agents that have known adverse events occurring beyond 7days after administration, this period must be extended beyond the time duringwhich adverse events are known to occur; the duration of this interval must bediscussed with the study chair

• Immunotherapy: At least 42 days after the completion of any type ofimmunotherapy, e.g. tumor vaccines

• Antibodies: >= 21 days must have elapsed from infusion of last dose ofantibody, and toxicity related to prior antibody therapy must be recovered tograde =< 1

• Corticosteroids: If used to modify immune adverse events related to priortherapy, >= 14 days must have elapsed since last dose of corticosteroid

• External beam radiation therapy (XRT): At least 14 days after local palliativeXRT (small port); at least 150 days must have elapsed if prior total bodyirradiation (TBI), craniospinal XRT or if >= 50% radiation of pelvis; at least 42 days must have elapsed if other substantial bone marrow (BM) radiation

• Stem cell infusion without TBI: No evidence of active graft vs. host diseaseand at least 56 days must have elapsed after transplant or stem cell infusion

• Patients must not have received prior exposure to selinexor

• For patients with solid tumors without known bone marrow involvement:

• • Peripheral absolute neutrophil count (ANC) >= 1000/mm^3
• • Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receivingplatelet transfusions for at least 7 days prior to enrollment)
• • Hemoglobin >= 8.0 g/dL at baseline (may receive red blood cell [RBC] transfusions)

• Patients with known bone marrow metastatic disease will be eligible for study ifthey meet the blood counts (may receive transfusions provided they are not known tobe refractory to red cell or platelet transfusions); these patients will not beevaluable for hematologic toxicity; at least 5 of every cohort of 6 patients must beevaluable for hematologic toxicity for the dose-escalation part of the study; ifdose-limiting hematologic toxicity is observed, all subsequent patients enrolled onPart A must be evaluable for hematologic toxicity

• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70ml/min/1.73 m^2 or

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

• =< 0.6 mg/dL (patients age 1 to < 2 years)

• =< 0.8 mg/dL (patients age 2 to < 6 years)

• =< 1 mg/dL (patients age 6 to < 10 years)

• =< 1.2 mg/dL (patients age 10 to < 13 years)

• =< 1.4 mg/dL (female patients age >= 13 years)

• =< 1.5 mg/dL (male patients age 13 to < 16 years)

• =< 1.7 mg/dL (male patients age >= 16 years)

• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age

• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3 xULN = 135 U/L; for the purpose of this study, the ULN for SGPT is 45 U/L

• Serum albumin >= 2 g/dL

• Serum amylase =< 1.5 x ULN

• Serum lipase =< 1.5 x ULN

• Patients with seizure disorder may be enrolled if on anticonvulsants and wellcontrolled

• Patients must be able to swallow tablets whole

• Part C: Archived paraffin-embedded tissue (20 unstained slides or a tumor block)from a prior resection must be available as a control for correlative studies; iftissue blocks or slides are unavailable, the study chair must be notified prior toenrollment

• All patients and/or their parents or legally authorized representatives must sign awritten informed consent; assent, when appropriate, will be obtained according toinstitutional guidelines

Exclusion Criteria:

• Pregnant or breast-feeding women will not be entered on this study, since there isyet no available information regarding human fetal or teratogenic toxicities; basedon its mechanism of action and findings in animals, selinexor may cause fetal harmwhen administered to a pregnant woman; pregnancy tests must be obtained in girls whoare post-menarchal; males with female partners of reproductive potential or femalesof reproductive potential may not participate unless they have agreed to use twoeffective methods of birth control- including a medically accepted barrier method ofcontraceptive method (e.g., male or female condom) for the entire period in whichthey are receiving protocol therapy and for at least 1 week following their lastdose of study drug; abstinence is an acceptable method of birth control

• Concomitant medications

• Corticosteroids: Patients receiving corticosteroids who have not been on astable or decreasing dose of corticosteroid for at least 7 days prior toenrollment are not eligible; if used to modify immune adverse events related toprior therapy, >= 14 days must have elapsed since last dose of corticosteroid

• Investigational drugs: Patients who are currently receiving anotherinvestigational drug are not eligible

• Anti-cancer agents: Patients who are currently receiving other anti-canceragents 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 thesafety monitoring requirements of the study are not eligible

• Patients with body mass index (BMI) < 3rd percentile for age, as defined by WHOcriteria for patients 1-2 years of age and Centers for Disease Control andPrevention (CDC) criteria for patients > 2 years of age, are not eligible

• Patients with grade 3 ataxia or grade >1 extrapyramidal movement disorder are noteligible

• Patients with known macular degeneration, uncontrolled glaucoma, or cataracts arenot eligible