This is a Phase I clinical trial evaluating abemaciclib (LY2835219), an inhibitor of cyclin dependent-kinases 4 and 6 (Cdk 4/6) in children and young adults with newly diagnosed diffuse intrinsic pontine glioma (DIPG) (Stratum A) and in relapsed/refractory/progressive malignant brain (Grade III/IV, including DIPG; MBT) and solid tumor (ST) patients (Stratum B).
Stratum A- Appropriate dose RT will be administered in 30-33 fractions over approximately 6 weeks for Stratum A patients. Treatment with abemaciclib (LY2835219) will start on the same day as radiation therapy (RT) and continue twice daily during and after RT for a maximum treatment duration of 2 years. Investigators plan to treat a maximum of 4 cohorts of research participants (dosage levels 1, 2, 3, and 4) with escalating doses of abemaciclib (LY2835219) starting with dose level 1 (80% of adult dose). A cycle is defined as 28 days and the first 6 weeks of therapy will constitute the dose-limiting toxicity (DLT)-evaluation period. Participants must take abemaciclib by mouth as intact capsules. Stratum B (no longer enrolling) - Abemaciclib (LY2835219) will be administered orally on a twice daily basis continuously for 28 days, which defines one cycle. The maximum treatment duration will be 2 years. Investigators plan to treat a maximum of 4 cohorts of research participants (dosage levels 1, 2, 3, and 4) with escalating doses of abemaciclib starting with dose level 1 (80% of adult dose). Dose escalation will be independent of Stratum A escalation. A cycle is defined as 28 days and the first 4 weeks of therapy will constitute the DLT-evaluation period. Participants must take abemaciclib by mouth as intact capsules. Enrollment for Stratum B closed December 27, 2018.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
53
Phoenix Children's Hospital
Phoenix, Arizona, United States
Children's Hospital Colorado
Aurora, Colorado, United States
Children's Healthcare of Atlanta, Egleston
Atlanta, Georgia, United States
Children's Healthcare of Atlanta, Scottish Rite
Atlanta, Georgia, United States
Abemaciclib Maximum Tolerated Dose (MTD) for Diffuse Intrinsic Pontine Glioma (DIPG)
The maximum dose of abemaciclib tolerated in participants with newly diagnosed diffuse intrinsic pontine glioma (DIPG).
Time frame: Week 6
Abemaciclib Maximum Tolerated Dose (MTD) for Recurrent/Refractory Solid Tumors
The maximum dose of abemaciclib in participants with recurrent/refractory solid tumors, including malignant tumors of the brain and spine.
Time frame: Week 6
Pharmacokinetics (PK): Predose Concentration (Cmin) of Abemaciclib
Time frame: Cycle 1 to End of Study (up to two years)
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Abemaciclib
Time frame: Cycle 1 to End of Study (up to two years)
Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of Abemaciclib
Time frame: Cycle 1 to End of Study (up to two years)
Number of participants with adverse events
The number of participants who experience adverse events.
Time frame: End of study (Up to two years)
Number of hematological toxicities
The number of hematological toxicities observed throughout the study among participants.
Time frame: End of study (Up to two years)
Number of non-hematological toxicities
The number of non-hematological toxicities observed throughout the study among participants.
Time frame: End of study (Up to two years)
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