A Study of Ribociclib and Everolimus Following Radiation Therapy in Children With Newly Diagnosed Non-biopsied Diffuse Pontine Gliomas (DIPG) and RB+ Biopsied DIPG and High Grade Gliomas (HGG)

Conditions

• Anaplastic Astrocytoma
• Bithalamic High Grade Glioma
• Brainstem Glioma
• Diffuse Intrinsic Pontine Glioma
• Glioblastoma
• High Grade Glioma
• Malignant Glioma of Brain

Eligibility Criteria

Sex

ALL

Age

12 Months - 30 Years

Healthy Volunteers

Not accepted

Interventions

• ribociclib — DRUG
  Oral capsule or liquid formula
• Everolimus — DRUG
  Oral tablets or dispersible tablets

Study Details

In this research study, we want to learn about the safety of the study drugs, ribociclib and everolimus, when given together at different doses after radiation therapy. We also want to learn about the effects, if any, these drugs have on children and young adults with brain tumors. We are asking people to be in this research study who have been diagnosed with a high grade glioma, their tumor has been screened for the Rb1 protein, and they have recently finished radiation therapy. If a patient has DIPG or a Bi-thalamic high grade glioma, they do not need to have the tumor tissue screened for the Rb1 protein, but do need to have finished radiation therapy. Tumor cells grow and divide quickly. In normal cells, there are proteins that control how fast cells grow but in cancer cells these proteins no longer work correctly making tumor cells grow quickly. Both study drugs work in different ways to slow down the growth of tumor cells. The researchers think that if the study drugs are given together soon after radiation therapy, it may help improve the effect of the radiation in stopping or slowing down tumor growth. The study drugs, ribociclib and everolimus, have been approved by the United States Food and Drug Administration (FDA). Ribociclib is approved to treat adults with breast cancer and everolimus is approved for use in adults and children who have other types of cancers. The combination of ribociclib and everolimus has not been tested in children or in people with brain tumors and is considered investigational. The goals of this study are: * Find the safest dose of ribociclib and everolimus that can be given together after radiation. * Learn the side effects (both good and bad) the study drugs have on the body and tumor. * Measure the levels of study drug in the blood over time. * Study the changes in the endocrine system that may be caused by the tumor, surgery or radiation.

Key Dates

Start date

Nov 14, 2017

Status verified

Jan 2023

Primary completion

Jul 31, 2020

Completion

Jul 31, 2022

Study Design

Enrollment

19 participants (actual)

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Dose level 1 (starting dose level) (participants </= 21yrs)
  Ribociclib administered orally; daily on days 1-21 each 28 day cycle; dose calculation age dependent (\>21 yrs of age 300mg daily (DIPG only); \</=21 yrs of age 120 mg/m2/day) Everolimus administered orally; daily on days 1 - 28 each 28 day cycle; dose calculation age dependent (\>21yrs 2.5mg/day (DIPG only); \</=21yr 1.2 mg/m2/day) BSA \>/=0.75m2
• Experimental: Dose level 2 (participants </= 21yrs)
  Ribociclib administered orally; daily on days 1-21 each 28 day cycle; 170 mg/m2/day Everolimus administered orally; daily on days 1 - 28 each 28 day cycle; 1.2 mg/m2/day BSA \>/=0.45m2
• Experimental: Dose level 3 (participants </= 21yrs)
  Ribociclib administered orally; daily on days 1-21 each 28 day cycle; 170 mg/m2/day Everolimus administered orally; daily on days 1 - 28 each 28 day cycle; 1.5 mg/m2/day BSA \>/=0.45m2
• Experimental: Dose level 1 (DIPG participants > 21yrs)
  Ribociclib administered orally; daily on days 1-21 each 28 day cycle; 300mg daily Everolimus administered orally; daily on days 1 - 28 each 28 day cycle; 2.5mg/day

Primary Outcome Measure

Number of adverse events [ Time Frame: 6 months ]

Locations (7)

Find similar trials in Washington D.C., DC

Related Studies

• Molecular Analysis of Samples From Patients With Diffuse Intrinsic Pontine Glioma and Brainstem Glioma
  Recruiting · Children's National Research Institute · Washington D.C., District of Columbia
• INdividualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT)
  PHASE2 · Recruiting · Patrick Wen, MD · Birmingham, Alabama
• International Diffuse Intrinsic Pontine Glioma (DIPG)/Diffuse Midline Glioma (DMG) Registry and Repository
  Recruiting · Children's Hospital Medical Center, Cincinnati · Cincinnati, Ohio
• Dabrafenib and/or Trametinib Rollover Study
  PHASE4 · Recruiting · Novartis Pharmaceuticals · Scottsdale, Arizona