| General information |
| Database: | DB00847 |
| Objective: | ZD6126 is a novel vasculartargeting agent that disrupts the endothelial tubulin cytoskeleton causing selective occlusion of tumor vasculature and extensive tumor necrosis. Thisphase I clinical study was conducted to evaluate the dose and administration schedule of ZD6126. |
| Authors: | LoRusso PM, et al |
| Title: | Phase I clinical evaluation of ZD6126, a novel vasculartargeting agent, in patients with solid tumors. |
| Journal: | Invest New Drugs. |
| Year: | 2008 |
| PMID: | 18219445 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | ZD6126
|
| Target: | Tubulin beta
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | solid tumors |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | Phase I clinical study |
| Key Patients Feature: | Adult patients with solid tumors refractory to existing treatments |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | pts received a 10min, singledose intravenous infusion of ZD6126 every 14 or 21 days. Subsequent dose escalation was performed, based on the incidence of adverse events (AEs) within the first cycle of drug administration. |
| Primary End Point: | Pharmacokinetic studies and safety profile |
| Secondary End Point: | NA |
| Patients Number: | 44 |
| Trial Results |
| DLT_MTD: | DLTs were defined as any CTC grade 3 or 4 that was not manageable with maximum supportive care; grade 4 neutropenia for more than 5 days; grade 4 thrombocytopenia of any duration; any cardiotoxic event (grade 1 cardiac arrhythmia, change in ejection fraction, blood pressure or heart rate, ECG abnormalities or elevation of cardiac enzymes).MTD was defined as the dose at which there is a 33% probability of experiencing a DLT within the first 21 days of drug administration. |
| Objective Response Rate: | 22.20% |
| 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): | Common AEs in the 21day study included abdominal pain, nausea, constipation and dyspnea. |
| Conclusions: | This study identified that ZD6126 administered every 2 or 3 weeks at 80 mgm2 was well tolerated, with mild but manageable gastrointestinal AEs. In approximately 11% (5 out of 44) of patients, ZD6126 was associated with cardiac events categorized as dose limiting toxicities (one patient with asymptomatic decreased left ventricular ejection fraction (LVEF), two with increased troponin concentrations, one with myocardial ischemia, and one with ECG signs of myocardial ischemia). |