Orally administered colony stimulating factor 1 receptor inhibitor PLX3397 in recurrent glioblastoma: an Ivy Foundation Early Phase Clinical Trials Consortium phase II study
Brigham and Women's Hospital · Memorial Sloan Kettering Cancer Center · +8 more institutions
Abstract
The colony stimulating factor 1 receptor (CSF1R) ligands, CSF1 and interleukin-34, and the KIT ligand, stem cell factor, are expressed in glioblastoma (GB). Microglia, macrophages, blood vessels, and tumor cells also express CSF1R, and depletion of the microglia reduces tumor burden and invasive capacity. PLX3397 is an oral, small molecule that selectively inhibits CSF1R and KIT, penetrates the blood-brain barrier in model systems, and represents a novel approach for clinical development.
We conducted a phase II study in patients with recurrent GB. The primary endpoint was 6-month progression-free survival (PFS6). Secondary endpoints included overall survival response rate, safety, and plasma/tumor tissue pharmacokinetics. Exploratory endpoints included pharmacodynamic measures of drug effect in blood and tumor tissue.
Citation impact
- FWCI
- 14.77
- Percentile
- 100%
- References
- 20
Authors
18- NBNicholas ButowskiCorresponding
Brigham and Women's Hospital, Memorial Sloan Kettering Cancer Center, The University of Texas MD Anderson Cancer Center, University of California, San Francisco, University of Utah, Huntsman Cancer Institute, UCLA Medical Center, Center for Neuro-Oncology, Dana-Farber Brigham Cancer Center, Plexxikon (United States)
- HCHoward Colman
Brigham and Women's Hospital, Memorial Sloan Kettering Cancer Center, The University of Texas MD Anderson Cancer Center, University of California, San Francisco, University of Utah, Huntsman Cancer Institute, UCLA Medical Center, Center for Neuro-Oncology, Dana-Farber Brigham Cancer Center, Plexxikon (United States)
- JDJohn de Groot
Brigham and Women's Hospital, Memorial Sloan Kettering Cancer Center, The University of Texas MD Anderson Cancer Center, University of California, San Francisco, University of Utah, Huntsman Cancer Institute, UCLA Medical Center, Center for Neuro-Oncology, Dana-Farber Brigham Cancer Center, Plexxikon (United States)
- AOAntonio Omuro
Brigham and Women's Hospital, Memorial Sloan Kettering Cancer Center, The University of Texas MD Anderson Cancer Center, University of California, San Francisco, University of Utah, Huntsman Cancer Institute, UCLA Medical Center, Center for Neuro-Oncology, Dana-Farber Brigham Cancer Center, Plexxikon (United States)
- LNLakshmi Nayak
Brigham and Women's Hospital, Memorial Sloan Kettering Cancer Center, The University of Texas MD Anderson Cancer Center, University of California, San Francisco, University of Utah, Huntsman Cancer Institute, UCLA Medical Center, Center for Neuro-Oncology, Dana-Farber Brigham Cancer Center, Plexxikon (United States)
Topics & keywords
- Cmax
- Pharmacokinetics
- Pharmacodynamics
- Clinical endpoint
- Medicine
- Surrogate endpoint
- Internal medicine
- Phases of clinical research
- Good health and well-being