Ribociclib and Everolimus in Treating Children With Recurrent or Refractory Malignant Brain Tumors
Condition: 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
MeSH terms: Neoplasms; Glioma; Brain Neoplasms; Ependymoma; Medulloblastoma; Diffuse Intrinsic Pontine Glioma; Rhabdoid Tumor; Recurrence
Study type: Interventional
Phase: Phase 1

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.
    

Detailed description: 
      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.
    

Intervention name(s): Everolimus; Laboratory Biomarker Analysis; Pharmacological Study; Ribociclib
Intervention type(s): Drug; Other; Other; Drug
Intervention description(s): Given PO; Correlative studies; Correlative studies; Given PO
Other intervention name(s): 42-O-(2-Hydroxy)ethyl Rapamycin; Afinitor; Certican; RAD 001; RAD001; Votubia; Zortress; Kisqali; LEE-011; LEE011
Intervention MeSH terms: Everolimus
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment