Study of the Combination of Crizotinib and Dasatinib in Pediatric Research Participants With Diffuse Pontine Glioma (DIPG) and High-Grade Glioma (HGG)
Phase I Study of the Combination of Crizotinib and Dasatinib in Pediatric Research Participants With Diffuse Pontine Glioma (DIPG) and High-Grade Glioma (HGG)
2 other identifiers
interventional
36
1 country
1
Brief Summary
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Nov 2012
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 17, 2012
CompletedFirst Posted
Study publicly available on registry
July 19, 2012
CompletedStudy Start
First participant enrolled
November 27, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 7, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
September 28, 2018
CompletedMarch 22, 2019
March 1, 2019
5.3 years
July 17, 2012
March 20, 2019
Conditions
Outcome Measures
Primary Outcomes (2)
Maximum tolerated dose of combination crizotinib and dasatinib in stratum A patients
6 weeks after start of therapy for last enrolled participant
Maximum tolerated dose of combination crizotinib and dasatinib in stratum B patients
6 weeks after start of therapy for last enrolled participant
Study Arms (1)
Chemotherapy
EXPERIMENTALResearch participants with high grade glioma or diffuse intrinsic pontine glioma will receive crizotinib and dasatinib.
Interventions
Starting dose level: * Initial Treatment Plan: 130 mg/m\^2 per dose * Modified Treatment Plan per Amendment 1.0: 165 mg/m\^2 per dose 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): once a day for 28 days Cycles 2-26 (28 days each): once a day
Starting dose level: 50 mg/m\^2 per dose 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): starting on day 3, once a day for 28 days Cycles 2-26 (28 days each): once a day
Eligibility Criteria
You may qualify if:
- Diagnosis of high-grade glioma (HGG) or diffuse intrinsic pontine glioma (DIPG). If histologic confirmation was obtained, diagnosis must be one of the following: anaplastic astrocytoma (WHO grade 3), anaplastic oligodendroglioma (WHO grade 3), anaplastic oligoastrocytoma (WHO grade 3), anaplastic ganglioglioma (WHO grade 3), pleomorphic xanthoastrocytoma with anaplastic features (WHO grade 3), malignant glioneuronal tumor, glioblastoma, or gliosarcoma (WHO grade 4)
- Age \> or = 2 years and \< or = 21 years
- Performance score \> or = 50 (Lansky for research participants \< or = 16 years and Karnofsky for those \> 16 years).
- Adequate organ function at the time of enrollment as follows:
- Bone marrow: Hemoglobin \> or = 8g/dL \[may have received packed red blood cell transfusion\], absolute neutrophil count (ANC) \> or = 1000/mm\^3, platelets \> or = 100,000/mm\^3 \[transfusion independent\])
- Renal: Normal serum creatinine based on age as shown below or GFR \> 70ml/min/1.73m\^2:
- Age \< or = 5 years: 0.8 mg/dL maximum
- Age 5 to 10 years: 1.0 mg/dL maximum
- Age 10 to 15 years: 1.2 mg/dL maximum
- Age \> 15 years: 1.5 mg/dL maximum
- Hepatic: SGPT and SGOT \< 3x the institutional upper limit of normal (ULN), total bilirubin concentration \< 1.5x the institutional ULN, albumin \> or = 2g/dL
- Female research participants \> or = 10 years of age or post-menarchal must not be pregnant (confirmed by serum or urine pregnancy test within 1 week of study enrollment) or breastfeeding
- Female research participants of childbearing age or males research participants of child fathering potential must agree to use safe contraceptive methods for the duration of the study and for 3 months thereafter
- Diagnosis of recurrent or progressive HGG or DIPG.
- Neurological deficits must be stable on a fixed or decreasing dose of dexamethasone for ≥7 days before study enrollment.
- +10 more criteria
You may not qualify if:
- Metastatic disease for stratum B only
- Concomitant use of other anticancer (except for corticosteroids) or experimental agents
- Use of enzyme-inducing anticonvulsants (EIACs). A minimum interval of 10 days between the last dose of EIAC and start of this therapy will be required for research participants who were previously receiving such medications.
- Pregnant or lactating patients
- Research participants with other clinically significant medical disorders that could compromise their ability to tolerate protocol therapy or would interfere with the study procedures or results
- Prior therapy with a PDGFR or c-Met inhibitor
- Original treatment design: Body surface area ≥ 1.8m2on dosage levels 3b, 4, and 5
- Modified treatment design: Body surface area \< 0.55 m\^2 for all dosage levels
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105, United States
Related Publications (1)
Gibson EG, Campagne O, Selvo NS, Gajjar A, Stewart CF. Population pharmacokinetic analysis of crizotinib in children with progressive/recurrent high-grade and diffuse intrinsic pontine gliomas. Cancer Chemother Pharmacol. 2021 Dec;88(6):1009-1020. doi: 10.1007/s00280-021-04357-4. Epub 2021 Sep 29.
PMID: 34586478DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Anna Vinitsky, MD
St. Jude Children's Research Hospital
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 17, 2012
First Posted
July 19, 2012
Study Start
November 27, 2012
Primary Completion
March 7, 2018
Study Completion
September 28, 2018
Last Updated
March 22, 2019
Record last verified: 2019-03