Study of the Combination of Crizotinib and Dasatinib in Pediatric Research Participants With Diffuse Pontine Glioma (DIPG) and High-Grade Glioma (HGG)
This is a phase I study to find the highest tolerable dose of crizotinib and dasatinib given in combination to patients with diffuse intrinsic pontine glioma (DIPG) and other types of high grade gliomas (HGG). Participants will receive escalating doses until the highest dose is determined. Participants will be enrolled in two strata: stratum A for recurrent/ progressive tumors and stratum B for recently diagnosed patients who have completed standard radiation therapy without progressive disease. Up to 7 dosage levels will be tested. Both drugs are taken orally daily, once per day. Correlative pharmacokinetic and biology studies are planned, as well as advanced methods of magnetic resonance imaging (MRI).
Diffuse Intrinsic Pontine Glioma
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Study of the Combination of Crizotinib and Dasatinib in Pediatric Research Participants With Diffuse Pontine Glioma (DIPG) and High-Grade Glioma (HGG)|
- Maximum tolerated dose of combination crizotinib and dasatinib in stratum A patients [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
- Maximum tolerated dose of combination crizotinib and dasatinib in stratum B patients [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
|Study Start Date:||November 2012|
|Estimated Study Completion Date:||September 2018|
|Estimated Primary Completion Date:||September 2016 (Final data collection date for primary outcome measure)|
Research participants with high grade glioma or diffuse intrinsic pontine glioma.
Starting dose levels:
The dose of a single agent will be increased by approximately 30% in each subsequent cohort until the MTD of this combination is reached.
The doses of each agent will not exceed their single-agent MTD already determined for children with recurrent solid tumors.
Cycle 1 (28 days):
Cycles 2-26 (28 days each):
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 ≤ 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).
- 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).
Please refer to this study by its ClinicalTrials.gov identifier: NCT01644773
|Contact: Tabatha Doyle, RNemail@example.com|
|United States, Tennessee|
|St. Jude Children's Research Hospital||Recruiting|
|Memphis, Tennessee, United States, 38105|
|Contact: Tabatha Doyle, RN 901-595-2544 firstname.lastname@example.org|
|Principal Investigator: Alberto Broniscer, MD|
|Principal Investigator:||Alberto Broniscer, MD||St. Jude Children's Research Hospital|