Ignite Creation Date:
2025-12-25 @ 2:00 AM
Ignite Modification Date:
2025-12-26 @ 5:05 AM
Study NCT ID:
NCT03355794
Status:
COMPLETED
Last Update Posted:
2023-01-13
First Post:
2017-11-22
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
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)
Sponsor:
Children's Hospital Medical Center, Cincinnati
Organization:
Study Overview
Official Title:
A Phase I 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)
Status:
COMPLETED
Status Verified Date:
2023-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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.
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.
Detailed Description:
This is a phase I study to determine: 1) the MTD and/or the recommended phase II dose (RP2D) of ribociclib and everolimus which can be safely administered during maintenance therapy for up to 24 courses following completion of radiation therapy with newly diagnosed non-biopsied DIPG and RB+ biopsied DIPG and HGG, 2) characterization of the pharmacokinetic profile of ribociclib and everolimus as combination maintenance therapy following completion of radiation therapy with newly diagnosed non-biopsied DIPG and RB+ biopsied DIPG and HGG.
Patients with RB+ tumors and non-biopsied DIPG will receive standard radiation therapy prior to enrollment followed by ribociclib and everolimus as maintenance therapy. Upon completion of radiation therapy, a 2 - 4 week break will occur and then ribociclib will be given orally daily for 21 days followed by a 7 day break every 28 days at 70% of the adult RP2D (300 mg) in combination with everolimus at 80% of the adult RP2D (2.5 mg) given orally once daily continuously for up to 24 courses. One course is equivalent to 28 days. Due to dosing concerns with the limited dosing capsules (50 mg and 200 mg are only available), dose escalations will have BSA restrictions to accommodate for variations from target doses and BSA adjusted actual dose. Two intra-patient dose-de-escalations will be allowed if dose limiting toxicities arise and may continue study treatment for up to 24 courses in the absence of disease progression or unacceptable toxicity.
Patients with RB+ tumors and non-biopsied DIPG will receive standard radiation therapy prior to enrollment followed by ribociclib and everolimus as maintenance therapy. Upon completion of radiation therapy, a 2 - 4 week break will occur and then ribociclib will be given orally daily for 21 days followed by a 7 day break every 28 days at 70% of the adult RP2D (300 mg) in combination with everolimus at 80% of the adult RP2D (2.5 mg) given orally once daily continuously for up to 24 courses. One course is equivalent to 28 days. Due to dosing concerns with the limited dosing capsules (50 mg and 200 mg are only available), dose escalations will have BSA restrictions to accommodate for variations from target doses and BSA adjusted actual dose. Two intra-patient dose-de-escalations will be allowed if dose limiting toxicities arise and may continue study treatment for up to 24 courses in the absence of disease progression or unacceptable toxicity.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: