Study of the Combination of Crizotinib and Dasatinib in Pediatric Research Participants With Diffuse Pontine Glioma (DIPG) and High-Grade Glioma (HGG)
NCT ID: NCT01644773
Last Updated: 2019-03-22
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE1
36 participants
INTERVENTIONAL
2012-11-27
2018-09-28
Brief Summary
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Detailed Description
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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).
Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Chemotherapy
Research participants with high grade glioma or diffuse intrinsic pontine glioma will receive crizotinib and dasatinib.
Crizotinib
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
Dasatinib
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
Interventions
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Crizotinib
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
Dasatinib
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
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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.
* Recovery to ≤ grade 1 from all significant toxicities of previous therapies.
* Irradiation: Interval from the last dose of local radiation therapy (RT), craniospinal RT, and palliative RT for symptomatic disease \> or = 3 months, \> or = 6 months, and \> or = 2 weeks before study enrollment, respectively
* Myelosuppressive chemotherapy: Interval \> or = 6 weeks and \> or = 4 weeks from last dose of nitrosourea and other chemotherapy drugs before study enrollment, respectively. However, interval must be \> or = 1 week from last dose of oral etoposide and other drugs administered at low doses (metronomic regimen) before study enrollment
* Small-Molecule Inhibitors: Interval \> or = 1 week from last dose before study enrollment. If a previously used agent has a prolonged half-life, the appropriate interval will be determined after consultation with the principal investigator
* Monoclonal Antibodies: Interval \> or = 3 half-lives before study enrollment. Such cases will need to be discussed with the principal investigator
* High-Dose Chemotherapy with Stem-Cell Rescue: Interval \> or = 3 months before study enrollment
* Cancer Vaccines and Convection-Enhanced Therapies: Interval \> or = 1 month before study enrollment
* Growth Factors: Interval \> or = 1 week and \> or = 2 weeks before study enrollment for standard and long-acting growth factors (e.g., pegfilgrastim), respectively
* Completion of local RT with or without concomitant chemotherapy including temozolomide and radiosensitizing agents (e.g., carboplatin, vorinostat) outside the context of a clinical trial. Any agent administered during RT should have a short half-life so that it should already be completely eliminated by the start of this therapy. If other agents were used concurrently with RT, they will need to be discussed with the principal investigator to assess eligibility
* Interval \> or = 4 weeks and \< or = 8 weeks from the completion of radiochemotherapy
Exclusion Criteria
* 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
2 Years
21 Years
ALL
No
Sponsors
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St. Jude Children's Research Hospital
OTHER
Responsible Party
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Principal Investigators
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Anna Vinitsky, MD
Role: PRINCIPAL_INVESTIGATOR
St. Jude Children's Research Hospital
Locations
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St. Jude Children's Research Hospital
Memphis, Tennessee, United States
Countries
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References
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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.
Related Links
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St. Jude Children's Research Hospital
Clinical Trials Open at St. Jude
Other Identifiers
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NCI-2012-01240
Identifier Type: REGISTRY
Identifier Source: secondary_id
SJHG12
Identifier Type: -
Identifier Source: org_study_id
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