A Phase I/II Study of Ribociclib,a CDK4/6 Inhibitor, Following Radiation Therapy

High Grade Glioma Clinical Trial

Official title: A Phase I/II Study of Ribociclib, a CDK4/6 Inhibitor, Following Radiation Therapy in Children With Newly Diagnosed Non-biopsied Diffuse Pontine Gliomas (DIPG) and RB+ Biopsied DIPG and High Grade Gliomas (HGG)

Status Terminated

Clinical Trial Summary

In this research study the investigators want to learn more about the effects, both good and bad, when the study drug Ribociclib is given after radiation therapy.

The investigators are asking people to be in this research study that have been newly diagnosed with a high grade glioma, and the tumor has been screened for the Rb1 protein, and have recently finished radiation therapy. Patients with a DIPG or a Bi-thalamic high grade glioma do not need to have 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 called cyclin-dependent kinases (CDK 4 and 6) that control cell division. Another protein Rb1 also controls cell division and works to stop cells from dividing so they do not become cancer cells. But in cancer, the CDK 4 and 6 proteins are out of control making the cells divide and grow quickly. The study drug, ribociclib stops the CDK 4 and 6 proteins. When the CDK 4 and 6 proteins are stopped, the normal Rb1 protein can now work to slow cell growth. For patients with HGG, to be in this study tumor tissue must have a normal Rb1 protein. The researchers think that if the study drug is given soon after radiation therapy, it may help improve the effect of the radiation in stopping the tumor from growing.

The study drug, Ribociclib is considered investigational as it has not yet been approved by the United States Food and Drug Administration. The study drug has been tested in children and adults with cancer in prior research studies.

Clinical Trial Description

Ribociclib has shown an acceptable toxicity profile in adults and pediatrics. Available data suggests that over 70% of DIPG patient have an intact RB and 90% HGG patients have expression of RB, therefore CDK4/6 inhibition is a suitable target. Given the dismal prognosis for children with DIPG and HGG, it is appropriate to evaluate the long term feasibility and early efficacy of Ribociclib following radiation therapy in patients with RB+ tumors. The aim of the upfront biopsy molecular studies proposed is to identify subgroups of patients who will benefit from the use of checkpoint inhibitors in the setting of intact RB pathway. This study will play a major role in moving the field of DIPG/HGG research forward as the investigators intend to reveal feasibility of upfront stereotactic biopsy and specific pathway directed therapy following radiation therapy with the ultimate goal to add additional targeted therapy in combination with Ribociclib resulting in improving the outcome for patients diagnosed with these fatal tumors.

The current proposal will be a novel pediatric study to obtain biopsy in DIPG prior to therapy and administer molecularly targeted therapy following radiation therapy in children with newly diagnosed DIPG and HGG. In this study, the investigators will assess the assess long-term feasibility and early efficacy of Ribociclib administered daily for 3 weeks and off one week every 28 days following radiation therapy for at least 6 courses and up to 12 courses in patients with newly-diagnosed non-biopsied DIPG and RB+ biopsied DIPG and HGG. Moreover, the investigators will approach this devastating disease with a multi-disciplinary team and evaluate the quality of life and functional outcome resulting in effective interventions. ;

Related Conditions & MeSH terms

• Bithalamic High Grade Glioma
• Diffuse Intrinsic Pontine Glioma
• Glioma
• High Grade Glioma

• NCT number: NCT02607124
• Study type: Interventional
• Source: Children's Hospital Medical Center, Cincinnati
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: April 2016
• Completion date: August 2018