ribociclib and everolimus in treating children with recurrent or refractory malignant brain tumors

Conditions: CNS Embryonal Tumor, Not Otherwise Specified; Malignant Glioma; Recurrent Atypical Teratoid/Rhabdoid Tumor; Recurrent Childhood Ependymoma; Recurrent Diffuse Intrinsic Pontine Glioma; Recurrent Medulloblastoma; Refractory Diffuse Intrinsic Pontine Glioma

Summary: this phase i trial studies the side effects and best dose of ribociclib and everolimus and to see how well they work in treating patients with malignant brain tumors that have come back or do not respond to treatment. ribociclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. drugs used in chemotherapy, such as everolimus, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. giving ribociclib and everolimus may work better at treating malignant brain tumors.

primary objectives: i. to estimate the maximum tolerated dose (mtd) and/or the recommended phase ii dose (rp2d) of ribociclib and everolimus in children with refractory or recurrent central nervous system (cns) tumors. (phase i) ii. to describe the toxicity profile and define the dose-limiting toxicities (dlts) of ribociclib and everolimus in children with refractory or recurrent cns tumors. (phase i) iii. to characterize the pharmacokinetics of ribociclib and everolimus in children with refractory or recurrent cns tumors, and the potential for drug-drug interactions between the two compounds in this population. (phase i) iv. to characterize ribociclib concentrations in tumor, and plasma in children with refractory or recurrent cns malignancies undergoing neurosurgical procedures. (surgical study) secondary objectives: i. to describe the response rate of relapsed and refractory malignant brain tumors to ribociclib and everolimus in the context of a phase i study. (phase i) ii. to explore the effect of ribociclib treatment on ki-67 by immunohistochemistry (ihc) by comparing archival and post-treatment tumor tissue. (surgical study) tertiary objectives: i. to increase knowledge of the genomic landscape of treatment-refractory pediatric cns tumors, including mechanisms of resistance and response. outline: this is a dose-escalation study. patients receive ribociclib orally (po) once daily (qd) on days 1-21 of course 1 and subsequent courses and days 2-21 of course 2, and everolimus po qd on days 3-28 of course 1 and days 1-28 of subsequent courses. patients who are undergoing surgery also receive ribociclib po qd on days 7-10 before surgery. treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity. patients with stable disease after 13 courses may continue receiving ribociclib and everolimus every 28 days for up to 13 additional courses in the absence of disease progression or unacceptable toxicity. after completion of study treatment, patients are followed up at 30 days.

Eligibility criteria:
inclusion criteria: * eligibility for screening * patients with a histologically confirmed diagnosis of high-grade glioma (hgg), medulloblastoma, cns embryonal tumor (not otherwise specified \[nos\]), ependymoma, or atypical teratoid rhabdoid tumor (atrt) that is recurrent, progressive or refractory * patients with recurrent diffuse intrinsic pontine glioma (dipg) with typical radiographic appearance who have undergone biopsy are eligible provided there is histologic confirmation of malignant glioma world health organization (who) ii-iv; rb1 screening for these patients is required only if adequate tissue is available * patients with recurrent brainstem tumors with an atypical presentation who have undergone biopsy are eligible provided there is histologic confirmation of malignant glioma who ii-iv; these patients must undergo rb1 screening; these patients must have radiographic evidence of progression * patients with secondary malignant gliomas will be eligible for this study but should conform to all other eligibility requirements; patients with low-grade gliomas are excluded * formalin fixed paraffin embedded tumor tissue (preferably from the most recent recurrence) must be available to assess rb1 protein status prior to enrollment on phase i or surgical study; if the subject has results from prior rb1 ihc testing in a clinical laboratory improvement act (clia)-certified laboratory the requirement for screening to assess rb1 protein status is waived * patients with recurrent diffuse intrinsic brain stem glioma (dipg) that has an atypical presentation must also submit the tumor tissue for rb1 protein status confirmation or provide previous testing results from a clia certified laboratory; patients who have been biopsied for atypical dipg but do not have sufficient tissue for rb1 screening are not eligible * body surface area (bsa) * patients enrolled on dose level -1 must have bsa \>= 0.55m\^2 * patients enrolled on dose level -0.5 must have bsa \>= 0.75m\^2 * patients enrolled on dose level 0 must have bsa \>= 0.55m\^2 * patients enrolled on dose level 1 must have bsa \>= 0.75m\^2 * patients enrolled on dose level 2 and 3 must have bsa \>= 0.45m\^2 * patients who are candidates for enrollment for the phase i or surgical studies must sign a screening consent and provide pre-trial tumor material for rb1 testing unless testing is not needed due to diagnosis or the availability of prior rb1 ihc results; the screening consent is to be obtained according to institutional guidelines * patients screened for this trial should be expected to meet the criteria for treatment * prior to study enrollment * phase i (stratum 1): patient has intact rb1 protein confirmed either from previous results or screened tissue; all testing must be performed in a clia certified laboratory; dipg patients with radiographically typical appearance will be waived from this requirement * phase i (stratum 1): patients with a histologically confirmed diagnosis of a primary cns tumor that is recurrent, progressive, or refractory; all tumors must have histologic verification of hgg, medulloblastoma, cns embryonal tumor (nos), ependymoma, or atrt; patients with low-grade gliomas are excluded * phase i (stratum 1): patients with progressive dipg, as defined by progressive neurologic abnormalities or worsening neurologic status not explained by causes unrelated to tumor progression (e.g., anticonvulsant or corticosteroid toxicity wean, electrolyte disturbances, sepsis, hyperglycemia, etc.), or an increase in the bi-dimensional measurement, taking as a reference the smallest disease measurement recorded since last treatment, or the appearance of a new tumor lesion since diagnosis * please note: * patients with a radiographically typical dipg, defined as a tumor with a pontine epicenter and diffuse involvement of more than 2/3 of the pons, are eligible without histologic confirmation * patients with pontine lesions that do not meet these radiographic criteria will be eligible if there is histologic confirmation of malignant glioma who ii-iv. these patients must have radiographic evidence of progression * surgical study (stratum 2): patients must have recurrent or refractory disease with a histological diagnosis at either the time of diagnosis or at the time of recurrence of one of the following: * hgg * medulloblastoma, * cns embryonal tumor (nos), * ependymoma, or * atrt * surgical study (stratum 2): patients for whom surgical intervention is clinically indicated (gross total resection or sub-total resection) at recurrence and are amenable to receiving ribociclib for 7 ? 10 days prior to resection * note: patients with dipg are excluded from the surgical study * bsa * patients enrolled on dose level -1 must have bsa \>= 0.55m2 * patients enrolled on dose level -0.5 must have bsa \>= 0.75m2 * patients enrolled on dose level 0 must have bsa \>= 0.55m2 * patients enrolled on dose level 1 must have bsa \>= 0.75m2 * patients enrolled on dose level 2 and 3 must have bsa \>= 0.45m2 * patients must have received prior therapy other than surgery and must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment * patients must have received their last dose of known myelosuppressive anticancer therapy at least 21 days prior to enrollment or at least 42 days if nitrosourea * biologic or investigational agent (anti-neoplastic): patient must have recovered from any acute toxicity potentially related to the agent and received their last dose of the investigational or biologic agent \>= 7 days prior to study enrollment * 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 * monoclonal antibody treatment and agents with known prolonged half-lives: at least three half-lives must have elapsed prior to enrollment. * patients must have had their last fraction of: * craniospinal irradiation (\> 24 gray \[gy\]) or total body irradiation \> 12 weeks prior to enrollment * focal irradiation \> 2 weeks prior to enrollment * \>= 3 months since autologous bone marrow/stem cell transplant prior to enrollment * neurologic status * patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to enrollment * patients with seizure disorders may be enrolled if seizures are well controlled on an anti-epileptic drug that is not a strong inducer or inhibitor of cyp3a4/5 are eligible * performance status * phase i: karnofsky performance scale (kps for \> 16 years of age) or lansky performance score (lps for =\ = 50 * surgical study: karnofsky performance scale (kps for \> 16 years of age) or lansky performance score (lps for =\ = 60 * patients who are unable to walk because of neurologic deficits, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score * absolute neutrophil count \>= 1.0 x 10\^9 cells/ l * \* platelets \>= 100 x 10\^9 cells/ l (unsupported, defined as no platelet transfusion within 7 days) * hemoglobin \>= 8g/dl (unsupported) * total bilirubin =\< 1.5 times institutional upper limit of normal (uln) * alanine aminotransferase (alt) (serum glutamate pyruvate transaminase \[sgpt\]) =\< 3 x institutional upper limit of normal (uln) * aspartate aminotransferase (ast) (serum glutamic-oxaloacetic transaminase \[sgot\]) =\< 3 x institutional upper limit of normal (uln) * albumin \>= 2 g/dl * serum creatinine based on age/gender; patients that do not meet the criteria but have a 24 hour creatinine clearance or glomerular filtration rate (gfr) (radioisotope or iothalamate) \>= 70 ml/min/1.73 m\^2 are eligible * patients who are receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to enrollment * patients must be off all colony- forming growth factor(s) for at least 1 week prior to enrollment (i.e. filgrastim, sargramostim or erythropoietin); 2 weeks must have elapsed if patients received long-acting formulations * female patients of childbearing potential must have a negative serum or urine pregnancy test * patients of childbearing or child fathering potential must be willing to use a medically acceptable form of birth control while being treated on this study; highly effective contraception methods include: * total abstinence when this is in line with the preferred and usual lifestyle of the patient; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception * combination of any of the two following * use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate \< 1%), for example hormone vaginal ring or transdermal hormone contraception * placement of an intrauterine device (iud) or intrauterine system (ius) * barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository * note: oral contraceptives are allowed but should be used in conjunction with a barrier method of contraception due to unknown effect of drug-drug interaction; in case of use of oral contraception, women should have been stable on the same pill for a minimum of 3 months before taking study treatment * female patients must agree not to breastfeed their infants while on study; patients of child fathering potential (defined as \> tanner stage 2) must use a condom during intercourse while taking the drug during treatment, for 8 weeks after stopping treatment and should not father a child in this period; a condom is required to be used also by vasectomized men during intercourse with a male or female partner in order to prevent delivery of the study drug via semen * the patient or parent/guardian is able to understand the consent and is willing to sign a written informed consent document according to institutional guidelines; assent, when appropriate, will be obtained according to institutional guidelines exclusion criteria: * patients who are otherwise deemed clinically unsuitable for surgical resection (applicable for surgical study only) * patients who are breast feeding * patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that would compromise the patient?s ability to tolerate protocol therapy, put them at additional risk for toxicity or would interfere with the study procedures or results * patients who are receiving any other anticancer or investigational or/and anti-neoplastic therapies, including chemotherapy, immunotherapy, target therapy, biological response modifiers * previous treatment with cdk4/6 inhibitors (such as pd-0332991, abemaciclib) and/or mtor inhibitors (such as sirolimus, temsirolimus or everolimus) * patients who are currently receiving treatment with agents that are known to cause corrected qt (qtc) prolongation or induce torsades de pointes * known need for major surgery within 14 days of the first dose of ribociclib and everolimus; please note: gastrostomy, insertion of a gastrostomy (g) tube, ventriculo-peritoneal shunt, endoscopic ventriculostomy and central venous access are not considered major surgery * patient is currently receiving any of the following medications and cannot be discontinued 7 days prior to enrollment: * known strong and moderate inducers or inhibitors of cyp3a4/5, including enzyme inducing anti-convulsant drugs (eiacds), grapefruit, grapefruit hybrids, pummelos, star-fruit, and seville oranges * substrates of cyp3a4/5 with a narrow therapeutic index * herbal preparations/medications (except for vitamins) including, but not limited to: st. john?s wort, kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (dhea), yohimbe, saw palmetto, black cohosh and ginseng; patients should stop using all herbal medications and dietary supplements at least 7 days prior to enrollment * clinically significant active cardiac disease, uncontrolled heart disease and/or a history of cardiac dysfunction including any of the following: * history of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 12 months prior to screening * history of documented congestive heart failure (new york heart association functional classification iii-iv) * documented cardiomyopathy * patient has a left ventricular ejection fraction (lvef) \< 50% as determined by echocardiogram (echo) * history of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality within 12 months of screening * long qt syndrome or known family history of idiopathic sudden death or congenital long qt syndrome, or any of the following: * risk factors for torsades de pointe (tdp) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia * concomitant use of medication(s) with a known risk to prolong the qt interval and/or days prior to starting study drug) or replaced by safe alternative medication * 12-lead electrocardiogram (ecg), any of the following cardiac parameters: * qtc \> 480 msec * hypertension defined as: * patients 1-17 years of age with blood pressure that is greater than or equal to the 95th percentile for age, height and gender at the time of enrollment; patients who are ≥ 18 years of age with blood pressure \> 140/90 mm of hg at the time of enrollment. * patient is currently receiving warfarin or other coumadin-derived anticoagulant for treatment, prophylaxis or otherwise. * patient has a known hypersensitivity to ribociclib or any of its excipients * patients with inability to return for required follow-up visits or obtain follow-up studies required to assess toxicity to therapy or to adhere to drug administration plan, other study procedures, and study restrictions.