| General information |
| Database: | DB00140 |
| Objective: | The purpose of thisphase 1 study of ENMD2076 was to determine the MTD, pharmacokinetic, and pharmacodynamic profiles and preliminary antitumor activity |
| Authors: | Diamond JR, et al |
| Title: | Phase I safety, pharmacokinetic, and pharmacodynamic study of ENMD2076, a novel angiogenic and Aurora kinase inhibitor, in patients with advanced solid tumors. |
| Journal: | Clin Cancer Res. |
| Year: | 2011 |
| PMID: | 21131552 |
| Trial Design |
| Clinical Trial Id: | NCT00658671 |
| Agent: | ENMD2076
|
| Target: | Aurora kinase A
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a phase I Safety, Pharmacokinetic, and Pharmacodynamic Study |
| Key Patients Feature: | Patients with refractory advanced solid malignancies (46 F, 21M; ages 3076) |
| Biomarker: | plasma levels of sVEGFR2 |
| Biomark Analysis: | Decreased plasma sVEGFR2 was observed posttreatment |
| Control Group Info: | single arm |
| Treatment Info: | patients were treated with ENMD2076 orally with continuous once daily dosing. Doses from 60 to 200 mg/m(2) were evaluated using a standard 3 (to 4) + 3 design. Pharmacokinetic parameters were studied on days 1, 28, and 30 to 35 of cycle 1. Expanded MTD cohorts included patients with ovarian cancer, colorectal cancer, and refractory solid tumors. |
| Primary End Point: | the MTD. |
| Secondary End Point: | the toxicity profile, pharmacokinetics, pharmacodynamic effects on plasma soluble VEGFR2, and preliminary antitumor activity. |
| Patients Number: | 67 |
| Trial Results |
| DLT_MTD: | Two patients experienced grade 3 hypertension at 200 mg/m(2), and additional grade 3 neutropenia events limited tolerability at this dose. An intermediate dose of 160 mg/m(2) was determined to be the MTD. |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most common drugrelated adverse events included hypertension, nausea/vomiting, and fatigue. |
| Conclusions: | ENMD2076 was well tolerated, had a linear pharmacokinetic profile, and showed promising antitumor activity, particularly in ovarian cancer. The recommendedphase 2 dose of ENMD2076 is 160 mg/m(2) administered orally once daily with continuous dosing. |