Entry Detail
| General information | |
| Database: | DB00505 |
| Objective: | To investigate the efficacy and safety of axitinib, an oral, potent, and selective inhibitor of vascular endothelial growth factor (VEGF) receptors 1, 2, and 3 in patients with metastatic renal cell carcinoma (mRCC) refractory to prior therapies that included, but were not limited to, sorafenib. |
| Authors: | Rini BI, et al |
| Title: | Phase II study of axitinib in sorafenibrefractory metastatic renal cell carcinoma. |
| Journal: | J Clin Oncol. |
| Year: | 2009 |
| PMID: | 19652060 |
| Trial Design | |
| Clinical Trial Id: | NCT00282048 |
| Agent: | axitinib |
| Target: | Macrophage colonystimulating factor 1 Vascular endothelial growth factor receptor 2 Plateletderived growth factor receptor |
| Cancer Type: | renal cell carcinoma |
| Cancer Subtype: | advanced renal cell carcinoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a singlestage, openlabel, multicenter, phase II study |
| Key Patients Feature: | Patients age 18 years or older with histologically documented mRCC ofany histologic subtype, prior nephrectomy, and prior failed treatment withsorafenib were enrolled between March and November 2006. Sorafenib failurewas defined as disease progression according to RECIST (Response EvaluationCriteria in Solid Tumors)18 or unacceptable treatmentrelated toxicity. Thenumber of additional prior failed regimens was unlimited. Additional eligibility criteria included the following: one or more RECISTdefined target lesionthat had not been irradiated; Eastern Cooperative Oncology Group performance status (ECOG PS) 1; adequate organ function; no evidence ofpreexisting uncontrolled hypertension ( 140/90 mmHg; antihypertensivemedication permitted); no active gastrointestinal bleeding or malabsorption;no uncontrolled brain metastases; and no major surgical procedure or anyradiation therapy within 4 weeks. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | patients with sorafenibrefractory mRCC received a starting dose of axitinib 5 mg orally twice daily |
| Primary End Point: | objective response rate (ORR) |
| Secondary End Point: | safety, duration of response, progression free survival (PFS), overall survival (OS), and patientreported outcomes. |
| Patients Number: | 62 |
| Trial Results | |
| DLT_MTD: | Allcausality grade 3 to 4 adverse eventsincluded handfoot syndrome (16.1%), fatigue (16.1%), hypertension (16.1%), dyspnea (14.5%), diarrhea (14.5%), dehydration (8.1%), and hypotension (6.5%). |
| Objective Response Rate: | In 62patients evaluable for response, the ORR was 22.6%, and the median duration of response was17.5 months. Median PFS and OS times were 7.4 months (95% CI, 6.7 to 11.0 months) and 13.6months (95% CI, 8.4 to 18.8 months), respectively. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 7.4 months (95% CI, 6.7 to 11.0 months) |
| Median OS A vs. C: | 13.6 months (95% CI, 8.4 to 18.8 months) |
| Adverse Event(agent arm): | Allcausality grade 3 to 4 adverse events included handfoot syndrome (16.1%), fatigue (16.1%), hypertension (16.1%), dyspnea (14.5%), diarrhea (14.5%), dehydration (8.1%), and hypotension (6.5%). |
| Conclusions: | Axitinib has antitumor activity in patients with mRCC refractory to prior VEGFtargeted therapy, including sorafenib. Toxicities were mild to moderate and were manageable. A randomized,phase III trial to compare axitinib with sorafenib in patients who have mRCC refractory to one prior firstline therapy regimen is underway. |