CX-4945 in Treating Patients with Recurrent SHH Medulloblastoma

Active:	Yes
Cancer Type:	Brain & Spinal Cord Tumor Brain Tumor Unknown Primary	NCT ID:	NCT03904862
Trial Phases:	Phase I Phase II	Protocol IDs:	PBTC-053 (primary) PBTC-053 NCI-2019-00180
Eligibility:	3 - 18 Years, Male and Female	Study Type:	Treatment
Study Sponsor:	Pediatric Brain Tumor Consortium
NCI Full Details:	http://clinicaltrials.gov/show/NCT03904862

Summary

This phase I/II trial studies the best dose and side effects of CX-4945, and how well it works in treating patients with sonic hedgehog (SHH) medulloblastoma that has come back (recurrent). CX-4945 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Objectives

PRIMARY OBJECTIVES:
I. To estimate the maximum tolerated dose (MTD) and recommend a Phase II dose of silmitasertib sodium (CX-4945) administered orally daily to skeletally-immature children with recurrent SHH (sonic hedgehog) medulloblastoma. (Phase I)
II. To describe the toxicity profile and define the dose-limiting toxicities associated with CX-4945 in children with recurrent SHH (sonic hedgehog) medulloblastoma. (Phase I)
III. To characterize the pharmacokinetics of CX-4945 administered on this schedule in skeletally-immature children with recurrent SHH medulloblastoma. (Phase I)
IV. To characterize the concentrations of CX-4945 in tumor after administration of CX-4945 and surgical resection. (Surgical study)
V. To establish the safety and characterize the toxicity of 1000 mg twice daily (BID) continuous dosing of CX-4945 in skeletally-mature patients with recurrent SHH medulloblastoma. (Phase II)
VI. To estimate the objective response rate associated with CX-4945 in skeletally-mature patients with recurrent SHH medulloblastoma. (Phase II)

SECONDARY OBJECTIVES:
I. To document preliminary antitumor activity of CX-4945 in skeletally-immature children with recurrent SHH medulloblastoma. (Phase I)
II. To perform a genomic analysis within the confines of a Phase I study to investigate correlation between response to treatment and the presence of specific genomic alterations and/or specific subgroups of disease. (Phase I)
III. To explore the ability of CX-4945 at MTD/ recommended phase II dose (RP2D) inhibits CK2-mediated signaling in tumor. (Surgical study)
IV. To characterize the pharmacokinetics of CX-4945 in skeletally-mature patients with recurrent SHH medulloblastoma. (Phase II)
V. To perform a genomic analysis within the confines of a Phase II study to investigate correlation between response to treatment and the presence of specific genomic alterations and/or specific subgroups of disease. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of silmitasertib sodium followed by a phase II study.

Patients receive silmitasertib sodium orally (PO) BID. Treatment repeats every 28 days for up to 52 cycles (26 for phase I and 26 for phase II) in the absence of disease progression or unacceptable toxicity.

SURGICAL STUDY: Patients receive silmitasertib sodium PO BID for 5-7 days prior to surgery. Within 2-4 weeks after surgery, patients receive silmitasertib sodium PO BID every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months 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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