Abemaciclib in Children With DIPG or Recurrent/Refractory Solid Tumors

Phase 1

Completed

Conditions: Diffuse Intrinsic Pontine Glioma
Brain Tumor, Recurrent
Solid Tumor, Recurrent
Neuroblastoma, Recurrent, Refractory
Ewing Sarcoma, Recurrent, Refractory
Rhabdomyosarcoma, Recurrent, Refractory
Osteosarcoma, Recurrent, Refractory
Rhabdoid Tumor, Recurrent, Refractory

Brief Summary: 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).

Detailed Description: 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.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Patients with uncontrolled infection
Patients with any concomitant significant medical illness that in the investigator's opinion cannot be adequately controlled with appropriate therapy, or that would impair the evaluation of side effects related to this treatment, alter drug metabolism or the tolerance to this treatment
Patients receiving any other anticancer or investigational drug therapy
Prior therapy with abemaciclib
Known mutation of Rb in tumor tissue
Prior history of QTC prolongation or QTC>450 ms on screening ECG.

Arm && Interventions

Group	Intervention	Description
Stratum B - enrollment is closed for this study arm	Abemaciclib	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.
Stratum A	Abemaciclib	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 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.

Primary Outcome Measures

Name	Time	Method
Abemaciclib Maximum Tolerated Dose (MTD) for Recurrent/Refractory Solid Tumors	Week 6	The maximum dose of abemaciclib in participants with recurrent/refractory solid tumors, including malignant tumors of the brain and spine.
Pharmacokinetics (PK): Predose Concentration (Cmin) of Abemaciclib	Cycle 1 to End of Study (up to two years)
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Abemaciclib	Cycle 1 to End of Study (up to two years)
Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of Abemaciclib	Cycle 1 to End of Study (up to two years)
Abemaciclib Maximum Tolerated Dose (MTD) for Diffuse Intrinsic Pontine Glioma (DIPG)	Week 6	The maximum dose of abemaciclib tolerated in participants with newly diagnosed diffuse intrinsic pontine glioma (DIPG).

Secondary Outcome Measures

Name	Time	Method
Number of participants with adverse events	End of study (Up to two years)	The number of participants who experience adverse events.
Number of hematological toxicities	End of study (Up to two years)	The number of hematological toxicities observed throughout the study among participants.
Number of non-hematological toxicities	End of study (Up to two years)	The number of non-hematological toxicities observed throughout the study among participants.

Locations (4): Children's Healthcare of Atlanta, Egleston
🇺🇸
Atlanta, Georgia, United States
Children's Healthcare of Atlanta, Scottish Rite
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Atlanta, Georgia, United States
Children's Hospital Colorado
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Aurora, Colorado, United States
Phoenix Children's Hospital
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Phoenix, Arizona, United States