In this research study the investigators want to learn more about the safety of the study drug, PTC596 has when taken during radiation. The investigators also want to learn about the effects, if any, these drugs have on children and young adults with brain tumors.
The investigators are asking people to be in this research study who have been diagnosed with a high grade glioma (HGG) including diffuse intrinsic pontine glioma (DIPG) to be in the research, because they have scheduled to have radiation to treat their cancer.
The study is divided into two parts. The goal of the first part is to find the dose of PTC596 that can be given with radiation without causing serious side effects. The purpose of this surgical study is to test the amount of a study drug that may be found in the tumor and blood when given prior to and during a planned surgery for removal of the recurrent tumor.
CONNECT1701: 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)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.
In this research study, we want to learn more about the effects of the study drug larotrectinib on children with brain tumors. We want to learn how well it works to shrink brain tumors when used alone or when given with standard chemotherapy or after radiation therapy.
The investigators are asking people to be in this research study who have been diagnosed with a high-grade glioma with a certain abnormal gene called NTRK. The investigators will evaluate the disease of the patients after they take the larotrectinib for 2 cycles. After taking the study drug for 2 cycles, the investigators will determine the next course of treatment. Patients will continue to receive either larotrectinib alone, larotrectinib with standard chemotherapy or larotrectinib alone after radiation therapy. The length of treatment depends on how well the patient is doing and which standard treatment the doctor thinks is best for them.
There is also a surgical cohort of the study where tumor samples and blood samples will be collected and sent to researchers to determine if larotrectinib is found in the tumor and how much is in the blood.
Investigators with preclinical data suggesting an interesting novel agent targeting high risk pediatric brain tumors are invited to contact CONNECT to submit a trial concept. Accepted trial concepts will be developed with the investigator and their institution through CONNECT.