Volitinib in Treating Participants With Recurrent or Refractory Primary CNS Tumors
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|ClinicalTrials.gov Identifier: NCT03598244|
Recruitment Status : Recruiting
First Posted : July 25, 2018
Last Update Posted : October 7, 2019
|Condition or disease||Intervention/treatment||Phase|
|Primary Central Nervous System Neoplasm Recurrent Diffuse Intrinsic Pontine Glioma Recurrent Malignant Glioma Recurrent Medulloblastoma Refractory Diffuse Intrinsic Pontine Glioma Refractory Malignant Glioma Refractory Medulloblastoma||Drug: Savolitinib||Phase 1|
I. To estimate the maximum tolerated dose (MTD) and recommend a phase II dose of volitinib (savolitinib) administered orally daily in children with refractory, progressive or recurrent primary CNS tumors.
II. To define and describe the toxicities of savolitinib in children with refractory, progressive or recurrent primary CNS tumors.
III. To characterize the pharmacokinetics of savolitinib in children with refractory, progressive or recurrent primary CNS tumors.
I. To preliminarily define the antitumor activity of savolitinib within the confines of a phase I study.
II. To perform a genomic analysis within the confines of a phase I study to investigate correlation between response to treatment (as measured by objective response or progression free survival [PFS]) and the presence of specific genomic alterations (e.g. MET amplification, chromosome 7q aneuploidy, MET mutation, or HGF amplification) and/or specific subgroups of disease.
OUTLINE: This is a dose-escalation study.
Participants receive volitinib orally (PO) once daily (QD). Treatment repeats every 28 days for up to 39 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, participants are followed up at 30 days, then periodically for up to 2 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||36 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Study of Savolitinib in Recurrent, Progressive or Refractory Primary CNS Tumors|
|Actual Study Start Date :||October 15, 2018|
|Estimated Primary Completion Date :||December 31, 2020|
|Estimated Study Completion Date :||December 31, 2020|
Experimental: Treatment (volitinib)
Participants receive volitinib PO QD. Treatment repeats every 28 days for up to 39 courses in the absence of disease progression or unacceptable toxicity.
- Maximum tolerated dose of volitinib defined as the highest dose level at which six patients have been treated with at most one patient experiencing a dose limiting toxicity and the next higher dose level has been determined to be too toxic [ Time Frame: Up to 30 days post treatment ]
- Recommend a phase II dose [ Time Frame: Up to 30 days post treatment ]
- Objective responses (complete response + partial response) [ Time Frame: Up to 2 years ]Will be described by dose and by histology. Prolonged stable diseases will also be reported in a descriptive fashion.
- Molecular analyses of tumors [ Time Frame: Up to 2 years ]Will be reported descriptively.
- Pharmacokinetic Parameters [ Time Frame: Up to 2 years ]Will be presented in tabular and graphical form. Pharmacokinetic parameters of interest, such as apparent volume of the central compartment (Vc/F), elimination rate constant (Ke), half-life (t1/2), apparent oral clearance (CL/F), and area under the plasma concentration time curve (AUC) will be estimated using compartmental methods. Dose proportionality in pharmacokinetic parameters will be investigated by performing one-way analysis of variance (ANOVA) on dose-normalized parameters.
- Population parameters [ Time Frame: Up to 2 years ]Will be estimated using nonlinear mixed effects modeling methods (NONMEM). This method estimates the population parameters and both the inter- and intra-subject variability. Once the population parameters and corresponding covariance matrix are estimated, individual estimates can be obtained using post hoc analysis.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03598244
|United States, California|
|Lucile Packard Children's Hospital Stanford University||Recruiting|
|Palo Alto, California, United States, 94304|
|Contact: Site Public Contact 800-694-0012 email@example.com|
|Principal Investigator: Michelle Monje|
|United States, Colorado|
|Children's Hospital Colorado||Recruiting|
|Aurora, Colorado, United States, 80045|
|Contact: Site Public Contact 303-764-5056 firstname.lastname@example.org|
|Principal Investigator: Kathleen M. Dorris|
|United States, Illinois|
|Lurie Children's Hospital-Chicago||Recruiting|
|Chicago, Illinois, United States, 60611|
|Contact: Site Public Contact 773-880-4562|
|Principal Investigator: Stewart Goldman|
|United States, New York|
|Memorial Sloan Kettering Cancer Center||Recruiting|
|New York, New York, United States, 10065|
|Contact: Site Public Contact 212-639-7592|
|Principal Investigator: Stephen W. Gilheeney|
|United States, Ohio|
|Cincinnati Children's Hospital Medical Center||Recruiting|
|Cincinnati, Ohio, United States, 45229|
|Contact: Site Public Contact 513-636-2799 email@example.com|
|Principal Investigator: Ralph Salloum|
|United States, Pennsylvania|
|Children's Hospital of Pittsburgh of UPMC||Recruiting|
|Pittsburgh, Pennsylvania, United States, 15224|
|Contact: Site Public Contact 412-692-8570 firstname.lastname@example.org|
|Principal Investigator: Alberto Broniscer|
|United States, Tennessee|
|St. Jude Children's Research Hospital||Recruiting|
|Memphis, Tennessee, United States, 38105|
|Contact: Site Public Contact 866-278-5833 email@example.com|
|Principal Investigator: Anna Vinitsky|
|United States, Texas|
|Texas Children's Hospital||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Site Public Contact 888-823-5923 firstname.lastname@example.org|
|Principal Investigator: Patricia A. Baxter|
|Principal Investigator:||Ralph Salloum||Pediatric Brain Tumor Consortium|