Abemaciclib in Children With DIPG or Recurrent/Refractory Solid Tumors

NCT02644460 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: IRB00083793
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 4

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).

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

Outcome Measures

Primary Outcomes (5)

• 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).

  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.

  Week 6

• 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)

Secondary Outcomes (3)

• 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)

Study Arms (2)

Stratum A

EXPERIMENTAL

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.

Drug: Abemaciclib

Stratum B - enrollment is closed for this study arm

EXPERIMENTAL

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.

Drug: Abemaciclib

Interventions

Abemaciclib DRUG

Also known as: LY2835219

Stratum A; Stratum B - enrollment is closed for this study arm

Eligibility Criteria

• Age: 2 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patient must have measurable or evaluable disease.
• Age must be ≥ 2 years and \< 25 years
• Body surface area (BSA) ≥ 0.5 m\^2
• Lansky (for participants ≤ 16 years) or Karnofsky (for participants \> 16 years) performance score ≥ 40 at the time of study enrollment
• Adequate organ function at the time of study enrollment as follows:
• Bone marrow: Absolute neutrophil count (ANC) ≥ 1,000/μL, platelet count ≥ 75,000/μL (transfusion independent for ≥ 7 days), hemoglobin concentration ≥ 8g/dL (may be transfused)
• Patients with bone marrow metastatic disease who do not meet the above criteria will be eligible to enroll in the study with the following count criteria. These patients will not be evaluable for hematologic toxicity or hematologic DLT.
• ANC \> 750/μL within 7 days prior to first dose of abemaciclib
• Platelet count \> 50,000/μL (may receive platelet transfusions) within 7 days prior to first dose of abemaciclib
• Hemoglobin ≥ 7.5 g/dL (may receive red blood cell (RBC) transfusions) within 7 days prior to first dose of abemaciclib
• Renal: Normal serum creatinine concentration based on age or glomerular filtration rate (GFR) \> 70 ml/min/1.73m\^2
• Hepatic: Total bilirubin concentration \< 1.5x the institutional upper limit of normal for age; serum glutamic pyruvic transaminase (SGPT) \< 10x the institutional upper limit of normal for patients on Stratum A. Stratum B patients must have SGPT \< 4x the institutional upper limit of normal.
• Cardiac: Adequate cardiac conductivity with corrected Q-T interval (QTC) of \< 450 ms on screening ECG.
• Female research participants of childbearing age must not be pregnant as confirmed by a serum or urine pregnancy test within 1 week of start of treatment. Participants must not be breast-feeding.
• All patients should submit an archival tumor biopsy specimen (collected at diagnosis or relapse). Patients who have no tumor tissue available may be permitted to participate after discussion with the principal investigator.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Emory University: lead

Study Sites (4)

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Children's Healthcare of Atlanta, Egleston

Atlanta, Georgia, 30322, United States

Location

Children's Healthcare of Atlanta, Scottish Rite

Atlanta, Georgia, 30342, United States

Location

Related Publications (1)

• Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14.

  PMID: 31401903 DERIVED

MeSH Terms

Conditions

Diffuse Intrinsic Pontine Glioma; Brain Neoplasms; Recurrence; Neuroblastoma; Sarcoma, Ewing; Rhabdomyosarcoma; Osteosarcoma; Rhabdoid Tumor

Interventions

abemaciclib

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Stem Neoplasms; Infratentorial Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Sarcoma; Myosarcoma; Neoplasms, Muscle Tissue; Neoplasms, Complex and Mixed

Study Officials

• Thomas Cash, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: December 15, 2015
• First Posted: December 31, 2015
• Study Start: February 1, 2016
• Primary Completion: October 10, 2023
• Study Completion: October 10, 2023
• Last Updated: October 26, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)