WP1066 in Children With Refractory and Progressive or Recurrent Malignant Brain Tumors

Inclusion Criteria: * Patients must have histologically confirmed progressive medulloblastoma, malignant glioma or any other recurrent/progressive malignant brain tumor, for which curative measures do not exist. Primary spinal tumors are eligible. DIPG and DMG H3K27M do not require histological confirmation. * Patients with DIPG and DMG with H3K27M who are post-radiation but have not exhibited tumor progression are also eligible. * Patients must have previously undergone standard-of-care treatment including surgery, radiation, and/or first line adjuvant chemotherapy prior to the experimental treatment (WP1066). * Patients must have recovered from the acute treatment related toxicities (defined as \< grade 1 if not defined in eligibility criteria) of all prior chemotherapy, immunotherapy or radiotherapy prior to entering this study. There is no upper limit to the number of prior therapies that is allowed. * Age \> 3 to 25 years. * Karnofsky or Lansky Performance Scale score \> 60%. * Patients must have normal organ and marrow function as defined below: * Absolute neutrophil count\> 1,000/mcL * Platelets\> 100,000/mcL * Total bilirubin within normal institutional limits * AST(SGOT)/ALT(SGPT)\< 5 x (\<10 x if taking steroids) institutional upper limit of normal * creatinine within normal institutional limits for age OR creatinine clearance\> 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal. * PT/PTT\< 1.5 x normal institutional standard * Patients with stable seizures (e.g., no seizures for ≥ 14 days and not requiring escalation or addition of anti-epileptic drugs) will be eligible. * Signed informed written consent obtained from patient if 18 years of age or older, or from guardian/legal representative if patient is less than 18 years of age Exclusion Criteria: * Patients must have received their last dose of known myelosuppressive anticancer therapy at least three (3) weeks prior to study enrollment or at least six (6) weeks if prior nitrosourea. * Biologic or investigational agent (anti-neoplastic): Patient must have received their last dose of the investigational or biologic agent ≥ 7 days prior to study enrollment. Antibodies: ≥ 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to Grade ≤ 1. Agents with prolonged half-lives: At least three half-lives must have elapsed prior to enrollment. * Immunotherapy: Patient must have completed immunotherapy (e.g. tumor vaccines, oncolytic viruses. etc.) at least 42 days prior to enrollment. * Radiation: Patients must have had their last fraction of: * Craniospinal irradiation ≥ 3 months prior to enrollment. * Other substantial bone marrow irradiation ≥ 6 weeks prior to enrollment * Local palliative XRT (small port) ≥2 weeks. * Stem Cell Transplant: Patient must be ≥ 12 weeks since autologous bone marrow/stem cell transplant prior to enrollment. * Surgery Patients must be fully recovered from all acute effects of prior surgical intervention. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to WP1066. * The enzymatic metabolism profile of WP1066 is unknown. Patients who are receiving drugs that significantly interact with the CYP450 enzyme(s) are ineligible. However, if they are switched to other medications with a 2-week washout window, they will be eligible. Patients are also excluded if they have been exposed within 7 days of planned first study treatment day to medications that are predominantly CYP2D6, 2C9 or 2C19 substrates, strong inhibitors or inducers, and sensitive substrates of CYP3A4 with narrow therapeutic range. * 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 situations that would limit compliance with study requirements. * No single lesion can be larger than 5 cm in maximal diameter. There may not be clinically significant midline shift or hydrocephalus. * The effects of WP1066 on the developing human fetus are unknown. Pregnant women are excluded from this study because WP1066 could potentially be teratogenic or have abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with WP1066, breastfeeding should be discontinued if the mother is treated with WP1066. Female subjects of childbearing potential should be willing to use 2 methods of birth control prior to study entry, during the study, and for 2 months after the last dose of the study drug or be surgically sterile. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year. 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. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of WP1066 administration. * HIV-positive patients receiving combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with WP1066. * The potential for further hemorrhaging with the use of WP1066 is unknown. It will be at the PIs discretion to enroll a patient who has a small, asymptomatic brain hemorrhage, but patients who have had symptomatic hemorrhages will be excluded. * Patients requiring escalation of the corticosteroid dose will be excluded, but patients receiving a stable or decreasing dose for at least one week prior to registration will be eligible. * The cardiac toxicities of WP1066 are unknown. Thus, patients who have a mean QTc interval \>450 ms at baseline will be excluded. Concomitant use of agents that prolong the QT interval will be avoided. * Patients with uncontrolled seizures or seizure requiring escalation or addition of anti-epileptic drugs will be excluded. * The use of medical cannabis and CBD oil is prohibited during the first 2 cycles of this protocol. Patients must be off cannabis oil for 3 days prior to enrollment