Abemaciclib in Children With Newly Diagnosed Diffuse Intrinsic Pontine Glioma, and in Children With Recurrent and Refractory Solid Tumors Including Malignant Brain Tumors
Overview
- Phase
- Phase 1
- Intervention
- Abemaciclib
- Conditions
- Diffuse Intrinsic Pontine Glioma
- Sponsor
- Emory University
- Enrollment
- 53
- Locations
- 4
- Primary Endpoint
- Abemaciclib Maximum Tolerated Dose (MTD) for Diffuse Intrinsic Pontine Glioma (DIPG)
- Status
- Completed
- Last Updated
- 2 years ago
Overview
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.
Investigators
Thomas Cash
Associate Professor
Emory University
Eligibility Criteria
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.
Arms & Interventions
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 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.
Intervention: Abemaciclib
Stratum B - enrollment is closed for this study arm
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.
Intervention: Abemaciclib
Outcomes
Primary Outcomes
Abemaciclib Maximum Tolerated Dose (MTD) for Diffuse Intrinsic Pontine Glioma (DIPG)
Time Frame: Week 6
The maximum dose of abemaciclib tolerated in participants with newly diagnosed diffuse intrinsic pontine glioma (DIPG).
Abemaciclib Maximum Tolerated Dose (MTD) for Recurrent/Refractory Solid Tumors
Time Frame: 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
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)
Secondary Outcomes
- Number of participants with adverse events(End of study (Up to two years))
- Number of hematological toxicities(End of study (Up to two years))
- Number of non-hematological toxicities(End of study (Up to two years))