| General information |
| Database: | DB00578 |
| Objective: | Cediranib is a highly potent inhibitor of vascular endothelial growth factor receptor (VEGFR) signalling. Preclinical and clinical data suggest that inhibition of the VEGFR and epidermal growth factor receptor (EGFR) pathways may be synergistic. Combination treatment with cediranib and gefitinib, an EGFR signalling inhibitor, was evaluated in patients with advanced solid tumours. |
| Authors: | Eberst L, et al |
| Title: | Phase I evaluation of cediranib, a selective VEGFR signalling inhibitor, in combination with gefitinib in patients with advanced tumours. |
| Journal: | BMC Cancer. |
| Year: | 2014 |
| PMID: | 25420707 |
| Trial Design |
| Clinical Trial Id: | NCT00502060 |
| Agent: | cediranib
|
| Target: | Vascular endothelial growth factor receptor 2
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | cediranib+gefitinib |
| Study Type: | an openlabel, multicentre study conducted in fourparts |
| Key Patients Feature: | Patients with advanced cancer refractory to standard treatment were recruited to one of the three centres in the Netherlands. The patients were required to have a lifeexpectancy of at least 12 weeks and a World Health Organisation performance status of 0-2.Primary tumour type(Renal Colorectal Lung(Histologies include non small cell lung cancer , broncoalveolar cell carcinoma, mesothelioma , pancoast, and lungnot otherwise specified )Skin/soft tissue Stomach Bone Pleura Head and neck Breast Pancreas Prostate Oesophagus Bladder PeritoneumPrimary tumour type(Renal Colorectal Lung(Histologies include non small cell lung cancer , broncoalveolar cell carcinoma, mesothelioma , pancoast, and lungnot otherwise specified )Skin/soft tissue Stomach Bone Pleura Head and neck Breast Pancreas Prostate Oesophagus Bladder PeritoneumPrimary tumour type(Renal Colorectal Lung(Histologies include non small cell lung cancer , broncoalveolar cell carcinoma, mesothelioma , pancoast, and lungnot otherwise specified )Skin/soft tissue Stomach Bone Pleura Head and neck Breast Pancreas Prostate Oesophagus Bladder PeritoneumPrimary tumour type(Renal Colorectal Lung(Histologies include non small cell lung cancer , broncoalveolar cell carcinoma, mesothelioma , pancoast, and lungnot otherwise specified )Skin/soft tissue Stomach Bone Pleura Head and neck Breast Pancreas Prostate Oesophagus Bladder Peritoneum |
| Biomarker: | levels of VEGF and soluble VEGFR2 |
| Biomark Analysis: | Pharmacodynamic assessments demonstrated changes in levels of VEGF and soluble VEGFR2 following treatment. |
| Control Group Info: | The patients received oncedaily oral doses of cediranib (2045mg) and gefitinib 250mg (part A1; n=16) or 500mg (part B1; n=44). A cohort expansionphase investigated the potential pharmacokinetic interaction of cediranib 30mg with gefitinib 250mg (part A2; n=15) or 500mg (part B2; n=15). |
| Treatment Info: | The patients received oncedaily oral doses of cediranib (2045mg) and gefitinib 250mg (part A1; n=16) or 500mg (part B1; n=44). A cohort expansionphase investigated the potential pharmacokinetic interaction of cediranib 30mg with gefitinib 250mg (part A2; n=15) or 500mg (part B2; n=15). |
| Primary End Point: | safety and tolerability |
| Secondary End Point: | pharmacokinetics, efficacy and pharmacodynamics |
| Patients Number: | 90 |
| Trial Results |
| DLT_MTD: | The most common adverse events were diarrhoea (84 [93%]), anorexia (63 [70%]) andfatigue (60 [67%]) |
| Objective Response Rate: | NA |
| Disease Control Rate: | 0.51 |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most common adverse events were diarrhoea (84 [93%]), anorexia (63 [70%]) and fatigue (60 [67%]). |
| Conclusions: | Combination treatment was generally well tolerated and showed encouraging antitumour activity in patients with advanced solid tumours. These results merit further exploration. |