Abemaciclib and Radiation Therapy in Treating Younger Patients with Newly Diagnosed Diffuse Intrinsic Pontine Glioma, Recurrent or Refractory Solid Tumors, or Malignant Brain Tumors

Active:	Yes
Cancer Type:	Brain & Spinal Cord Tumor Neuroblastoma Sarcoma	NCT ID:	NCT02644460
Trial Phases:	Phase I	Protocol IDs:	AFLACST1501 (primary) NCI-2015-02256 IRB00083793
Eligibility:	2 - 25 Years, Male and Female	Study Type:	Treatment
Study Sponsor:	Children's Healthcare of Atlanta - Egleston
NCI Full Details:	http://clinicaltrials.gov/show/NCT02644460

Summary

This phase I trial studies the side effects and best dose of abemaciclib when given together with radiation therapy in treating younger patients with newly diagnosed diffuse intrinsic pontine glioma (a type of central nervous system tumor that forms from glial [supportive] tissue of the brain and spinal cord), or solid tumors that have come back (recurrent) or does not respond to treatment (refractory), or malignant brain tumors. Abemaciclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving abemaciclib together with radiation therapy may be a better treatment in patients with diffuse intrinsic pontine glioma, solid tumors, or malignant brain tumors.

Objectives

PRIMARY OBJECTIVES:
I. To estimate the maximum tolerated dose (MTD) of abemaciclib (LY2835219) administered concurrently with radiation therapy (RT) in pediatric research participants with newly diagnosed diffuse intrinsic pontine glioma (DIPG).
II. To estimate the MTD of abemaciclib (LY2835219) in children and young adults with recurrent/refractory solid tumors, including malignant tumors of the brain and spine (World Health Organization [WHO] grade III/IV).
III. To characterize the pharmacokinetics of abemaciclib (LY2835219) in pediatric patients and relate drug exposure to toxicity.

SECONDARY OBJECTIVES:
I. To characterize toxicities and/or adverse events associated with the chronic use of abemaciclib (LY2835219).
II. To evaluate changes in phosphorylation of histone H3, retinoblastoma (Rb) and/or topoisomerase (topo)II alpha inhibition in peripheral blood mononuclear cells and investigate the possible relationship between these changes, plasma drug levels of abemaciclib, and outcome measures.
III. To evaluate cyclin-dependent kinase (Cdk)4/6, cyclin D1 (CCND1) and Rb protein and messenger ribonucleic acid (mRNA) expression in tumor tissue where available.
IV. To evaluate the coding transcriptome (RNA sequencing) of tumor tissue where available.
V. To analyze the cargo of protein and mRNA in exosomes in patient plasma as a means of “liquid biopsy” in comparison to primary tumor tissue, as available.
VI. To assess the pattern of failure in newly diagnosed DIPG participants.

OUTLINE: This is a dose escalation study of abemaciclib. Patients are assigned to 1 of 2 treatment strata.

STRATA A NEWLY DIAGNOSED DIPG: Patients receive abemaciclib orally (PO) twice daily (BID) on days 1-28 and undergo 3-dimensional (3-D) conformal radiation therapy once daily (QD) 5 days a week for 6 weeks. Courses with abemaciclib repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.

STRATA B RECURRENT, REFRACTORY OR PROGRESSIVE SOLID AND MALIGNANT BRAIN TUMORS: Patients receive abemaciclib PO BID on days 1-28. Courses repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 3, 6, 9, 12, 15, 18, 24, 30, and 36 months, and then periodically for 2 years.

Treatment Sites in Georgia

Aflac Cancer and Blood Disorders Center of Children’s at Egleston
1405 Clifton Road NE
3rd Floor
Atlanta, GA 30322
404-785-0853
www.choa.org

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