Entry Detail
| General information | |
| Database: | DB00694 |
| Objective: | Thisphase I study investigated cediranib, an oral inhibitor of vascular endothelial growth factor signalling in combination with saracatinib, an oral Src inhibitor. safety/tolerability. Secondary assessments included pharmacokinetics and preliminary efficacy. |
| Authors: | Trarbach T, et al |
| Title: | Phase I openlabel study of cediranib, an oral inhibitor of VEGF signalling, in combination with the oral Src inhibitor saracatinib in patients with advanced solid tumours. |
| Journal: | Invest New Drugs |
| Year: | 2012 |
| PMID: | 21989836 |
| Trial Design | |
| Clinical Trial Id: | study codes NCT00475956;2171IL/0014 |
| Agent: | cediranib and saracatinib |
| Target: | cediranib: Vascular endothelial growth factor receptor 2 saracatinib: Protooncogene tyrosineprotein kinase SRC Abl |
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | cediranib+saracatinib |
| Study Type: | Phase I openlabel a doseescalation study |
| Key Patients Feature: | Eligible patients had advanced solid tumours (excludingprostate cancer as the maximum tolerated dose [MTD] ofcediranib had already been defined as 20 mg [30]) that wererefractory to standard therapies, with one or more measurable lesions as assessed by Response Evaluation Criteria InSolid Tumours (RECIST version 1.0), World Health Organization (WHO) performance status 0-2 and lifeexpectancy more than and equal to 12 weeks. Key exclusion criteria includeduntreated, unstable brain or meningeal metastases, significant haematopoietic, hepatic, gastrointestinal or renaldysfunction, significant recent haemorrhage or haemoptysis, poorly controlled hypertension, concomitant anticancertherapy and major thoracic or abdominal surgery within theprevious 2 weeks. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm escalating dose |
| Treatment Info: | Patients with advanced solid tumours received cediranib 20, 30 or 45 mg/day for 7 days followed by daily treatment with cediranib at the same dose plus saracatinib 175 mg/day. |
| Primary End Point: | safety and tolerability |
| Secondary End Point: | the steadystate pharmacokinetics and preliminary evaluation of the efficacy of cediranib and saracatinib when given in combination. |
| Patients Number: | 39 |
| Trial Results | |
| DLT_MTD: | There was onedoselimiting toxicity (hypertension; 45 mg cohort). Themost common adverse events were hypertension (67%), diarrhoea (62%), dysphonia (46%) and fatigue (39%). |
| Objective Response Rate: | 22/35 evaluable patients had a best response of stabledisease. |
| 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): | There was one doselimiting toxicity (hypertension; 45 mg cohort). The most common adverse events were hypertension (67%), diarrhoea (62%), dysphonia (46%) and fatigue (39%). There was no evidence of a clinically significant effect of saracatinib on cediranib pharmacokinetics and vice versa. |
| Conclusions: | All cediranib doses they were tolerated; hotheyver, in patients with advanced solid tumours, for combination with saracatinib 175 mgday, cediranib 20 or 30 mgday was more sustainable than 45 mgday. |