Why was this study done?
Diffuse intrinsic pontine glioma (DIPG) and high-grade glioma (HGG) are cancers of the brain or spinal cord. Children with DIPG or HGG do not survive if their disease progresses or comes back after therapy. We desperately need new treatments for these patients.
This study combined two new drugs called crizotinib and dasatinib. Both drugs were thought to block proteins that cause cancer to grow and spread. These drugs had been used to treat lung cancer and leukemia in adults. But they had never been used to treat cancer in children.
The study’s main goals were to:
- Find the highest dose of these drugs that could be safely given to patients
- Learn more about how the body takes up, breaks down, and gets rid of crizotinib given alone or along with dasatinib
- Learn about the side effects of this treatment
When was this study done?
The study opened in November 2012 and closed in September 2018.
What did the study consist of?
Patients took crizotinib by mouth once a day. They added dasatinib (also taken by mouth) on the third day of therapy. The patients took both drugs every day. Each patient filled out a medication diary and had regular follow-up tests.
What did we learn from this study?
Because of this study, we better understand how crizotinib and dasatinib work. When used together, they caused some side effects like diarrhea, fatigue, low white blood cell counts and other side effects. As a result, most of the patients had to stop taking these drugs. The treatment did not result in tumor shrinkage.
What are the next research steps as a result of this study?
This treatment caused side effects without producing tumor shrinkage. We will not use these drugs together in the future for children with DIPG and HGG. We will use what we learned in this study to find better treatment options for these patients.
For more information
Please talk with your child’s St. Jude doctor about questions or concerns you have as a result of this study.
Publications generated from this study
Phase 1 trial, pharmacokinetics, and pharmacodynamics of dasatinib combined with crizotinib in children with recurrent or progressive high-grade and diffuse intrinsic pontine glioma. Broniscer A, Jia S, Mandrell B, Hamideh D, Huang J, Onar-Thomas A, Gajjar A, Raimondi SC, Tatevossian RG, Stewart CF. Pediatr Blood Cancer. 2018 Jul;65(7):e27035. doi: 10.1002/pbc.27035. Epub 2018 Mar 7.
https://pubmed.ncbi.nlm.nih.gov/29512900/
Population pharmacokinetic analysis of crizotinib in children with progressive/recurrent high-grade and diffuse intrinsic pontine gliomas. Gibson EG, Campagne O, Selvo NS, Gajjar A, Stewart CF. Cancer Chemother Pharmacol. 2021 Sep 29. doi: 10.1007/s00280-021-04357-4. Online ahead of print.
https://pubmed.ncbi.nlm.nih.gov/34586478/