A Phase I, Multi-Center, Open-Label, Treatment Duration Increment, Expansion, Safety, and Pharmacodynamic Study of Silmitasertib (CX-4945) Administered Orally Twice Daily to Patients with Advanced Basal Cell Carcinoma
A Pediatric Brain Tumor Consortium Phase I/ II and Surgical Study of Silmitasertib (CX-4945) in Patients with Recurrent SHH Medulloblastoma
A Phase I/II Study of Silmitasertib (CX-4945) in Combination with Gemcitabine plus Cisplatin in the Frontline Treatment of Patients with Cholangiocarcinoma
Senhwa Biosciences, Inc.
Part I: 3-6
Part II: 20
The primary objective of this study is to determine the recommended phase II dose (RP2D) and schedule of CX-4945 in patients with locally advanced or metastatic basal cell carcinoma (BCC).
To establish the safety and tolerability of CX-4945 in this patient population.
To assess preliminary evidence of antitumor effects in this patient population by documentation of objective responses using standardized criteria.
To evaluate the effect of CX-4945 treatment on the Hh signaling pathway using qRT-PCR in fresh-frozen tissue from patients with locally advanced BCC obtained at baseline and following CX-4945 treatment.
Pediatric Brain Tumor Consortium
St. Jude Children's Research Hospital
National Cancer Institute (NCI)
Phase I Trial (skeletally-immature patients): 6-10 patients per year
Surgical cohort: 2-3 patients per year Phase II Trial (skeletally-mature patients): 10-12 patients per year
Phase I Trial ( Dose Escalation Phase)
To estimate the maximum tolerated dose (MTD) and/or the recommended phase II dose (RP2D).
To describe the toxicity profile and define the dose-limiting toxicities (DLTs) and to characterize the pharmacokinetics profile.
To document preliminary antitumor activity
To estimate the maximum tolerated dose (MTD) and/or the recommended phase II dose (RP2D)
To characterize the concentrations of CX-4945 in tumor after administration of CX-4945 and surgical resection
To explore the ability of CX-4945 at the MTD/ RP2D to inhibit CK2-mediated signaling in tumor
Phase II Trial (to establish the safety of 1000mg/m2 BID given continuously)
To establish the safety and characterize the toxicity of 1000mg/m2 BID continuous dosing of CX-4945
To estimate the objective response rate
To characterize the pharmacokinetics
To perform a genomic analysis within the confines of a Phase II study
Senhwa Biosciences, Inc.
216, for details see the Objectives below
Phase I (Dose Escalation Phase/Completed with 51 pts enrolled )
To determine the combination maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of CX-4945
To establish the pharmacokinetic (PK) profile
Phase II (Randomized Study Phase/ On-going, estimated recruitment 165 pts)
Comparison of the progression-free survival (PFS) between the test and control arms
Comparison of the overall-response rate (ORR) between the test and control arms
Comparison of the number of patient who transition to surgical resection between the test and control arms
Comparison of the overall survival rates (OS) between the test and control arms