A Phase I/II Study of CX-4945 in Combination with Gemcitabine plus Cisplatin in the Frontline Treatment of Patients with Cholangiocarcinoma
A Phase 1, Open-Label, Dose Escalation, Safety, Pharmacokinetic, and Pharmacodynamics Study of Intravenously Administered CX-5461 in Patients with Advanced Hematologic Malignancies
A Phase I Study of CX5461
A Phase I, Multi-Center, Open-Label, Treatment Duration Increment, Expansion, Safety, and Pharmacodynamic Study of 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 CX-4945 in Patients with Recurrent SHH Medulloblastoma
Phase I (Dose Escalation Phase/Completed with 51 pts enrolled )Primary endpoint
- 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)Primary endpoint
- 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
- To determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of intravenously administered CX-5461 when used intravenously in haematologic cancers.
- To establish the safety profile of CX-5461 at the MTD.
- To establish the pharmacokinetic (PK) profile of CX-5461.
- To observe patients for evidence of CX-5461 biological activity using pharmacodynamic (PD) assessments.
- To observe patients for preliminary antitumor activity of CX-5461.
- To evaluate the mechanism of action of CX-5461 in haematologic cancers.
- To identify predictive biomarkers of efficacy in human haematologic cancers.
Senhwa Biosciences, Inc.
Stand Up To Cancer (SU2C) Canada - Canadian Breast Cancer Foundation Grant
10-20 patients with metastatic breast cancer for Expansion stage
Phase I Escalation (Solid tumors)
- To determine the recommended phase II dose (RP2D) and schedule of CX5461 in patients with solid tumors.
- To establish the safety and tolerability of CX5461 given intravenously to patients with solid tumors.
- To determine the pharmacokinetics of CX5461 given intravenously in patients with solid tumors.
Phase I Expansion: (Breast cancer)
- To explore the relationship between germline HRD aberrations and outcomes of CX5461, including efficacy and toxicity.
- To evaluate CX5461 drug levels in skin and tumor.
- To evaluate biomarkers of response to CX5461
- paired biopsies (all patients after Amendment #3);
- paired tumour biopsies (mandatory for 6-8 patients at RP2D)
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.
National Cancer Institute (NCI)
- 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