Phase I Study of the Combination of Crizotinib and Dasatinib in Pediatric Research Participants With Diffuse Pontine Glioma (DIPG) and High-Grade Glioma (HGG)
The Rolling 6 design will be used to estimate the maximum tolerated dose (MTD) and determine
the dose-limiting toxicity (DLT) of the combination of escalating doses of crizotinib and
dasatinib. Our goal is to accrue research participants for both stratum A and B. However,
it is our expectation that the accrual of research participants to stratum B will proceed at
a slower pace. Therefore, initially the strategy of dose escalation will be exclusively
based on research participants treated at stratum A until the MTD of this combination is
reached. Until the MTD of this combination is reached for research participants in stratum
A, accrual of research participants in stratum B will be allowed at the highest dosage level
which has already been deemed to be safe (i.e., no DLTs in three research participants or <
or = 1 DLT in six research participants). No research participants will be accrued to
stratum B until at least one dosage level has been confirmed to be safe in stratum A. Once
the MTD for stratum A is reached, we will accrue research participants at this same dosage
level to stratum B following the rules of the Rolling 6 design. If the MTD for stratum A is
well tolerated among research participants in stratum B, we will proceed with dose
escalation for research participants in stratum B based on the same rules of the Rolling 6
design. This strategy is based on the premise that research participants who are more
heavily pre-treated (stratum A) may not tolerate therapy as well as those with minimal
previous treatment (stratum B).
Primary Objectives:
- To estimate the MTD of the combination of crizotinib (c-Met and ALK inhibitor) and
dasatinib (bcr-abl, PDGFRA and B, src, lck, yes, and c-kit inhibitor) in pediatric
research participants with recurrent or progressive DIPG and other HGGs (stratum A).
- To estimate the MTD of the combination of crizotinib and dasatinib in research
participants with DIPG or HGG who completed RT within a short interval prior to
enrollment but have not experienced disease progression (stratum B).
Interventional
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of combination crizotinib and dasatinib in stratum A patients
3 years
Yes
Alberto Broniscer, MD
Principal Investigator
St. Jude Children's Research Hospital
United States: Institutional Review Board
SJHG12
NCT01644773
August 2012
August 2015
Name | Location |
---|---|
St. Jude Children's Research Hospital | Memphis, Tennessee 38105-2794 |