Entry Detail
| General information | |
| Database: | DB00126 |
| Objective: | This firstinhumanphase I study evaluated doselimiting toxicities (DLT) and defined a phase II recommended dose (RD) for CUDC101, as a 1hour intravenous (i.v.) infusion for 5 consecutive days every 2 weeks. |
| Authors: | Shimizu T, et al |
| Title: | Phase I firstinhuman study of CUDC101, a multitargeted inhibitor of HDACs, EGFR, and human epidermal growth factor receptor 2 in patients with advanced solid tumors. |
| Journal: | Clin Cancer Res. |
| Year: | 2014 |
| PMID: | 25107918 |
| Trial Design | |
| Clinical Trial Id: | NA |
| Agent: | CUDC101 |
| Target: | Erbb2 tyrosine kinase receptor Epidermal growth factor receptor |
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | This firstinhumanphase I, openlabel, multicenter study |
| Key Patients Feature: | patients with advanced solid tumors |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | escalating doses of CUDC101 (range, 75300 mg/m(2)/day) following a standard 3 + 3 dose escalation design. |
| Primary End Point: | the MTD of CUDC101 administered as a 1 hour intravenous (i.v.) infusion on 5 consecutive days every 14 days, and to assess the safety and tolerability, the PK profile, PD measurements, and preliminary evidence of antitumor activity in patients with advanced solid malignancies. |
| Secondary End Point: | NA |
| Patients Number: | 25 |
| Trial Results | |
| DLT_MTD: | The MTD was determined to be 275 mg/m(2).DLTs occurred in 1 patient in the 275mg/m(2) dose cohort (grade 2 serum creatinine elevation, n = 1) and 3 patients in the 300mg/m(2) dose cohort (grade 2 serum creatinine elevation, n = 2; pericarditis, n = 1), all of which were transient and reversible. CUDC101 exposure increased linearly with the mean maximum concentration (Cmax), clearance (CL), volume of distribution at steadystate (Vdss), area under curve (AUC), and terminal elimination halflife (t1/2) at the MTD dose of 9.3 mg/L, 51.2 L/h, 39.6 L, 9.95 h.ng/mL and 4.4 hours. |
| Objective Response Rate: | NA |
| Disease Control Rate: | One patient with gastric cancer had a partial response and 6 patients had stable disease. |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Common grade 1/2 adverse events included nausea, fatigue, vomiting, dyspnea, pyrexia, and dry skin. |
| Conclusions: | CUDC101 administered by 1hour i.v. infusion for 5 consecutive days every 2 weeks was generally well tolerated with preliminary evidence of antitumor activity. A dose of 275 mg/m(2) is recommended for further clinical testing. |