| General information |
| Database: | DB00205 |
| Objective: | Cabozantinib (XL184) is an orally bioavailable tyrosine kinase inhibitor with activity against MET and vascular endothelial growth factor receptor 2. They evaluated the activity of cabozantinib in patients with castrationresistant prostate cancer (CRPC) in a phase II randomized discontinuation trial with an expansion cohort. |
| Authors: | Smith DC, et al |
| Title: | Cabozantinib in patients with advanced prostate cancer: results of a phase II randomized discontinuation trial. |
| Journal: | J Clin Oncol. |
| Year: | 2013 |
| PMID: | 23169517 |
| Trial Design |
| Clinical Trial Id: | NCT00940225 |
| Agent: | cabozantinib
|
| Target: | Hepatocyte growth factor receptor, Vascular endothelial growth factor receptor 2
|
| Cancer Type: | prostate cancer |
| Cancer Subtype: | advanced castrationresistant prostate cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a phase II randomized discontinuation trial with an expansion cohort |
| Key Patients Feature: | Men with metastatic castrateresistant prostate cancer |
| Biomarker: | Serum total alkaline phosphatase and plasma crosslinked Cterminal telopeptide of type I collagen were reduced by more than and equal to 50% in 57% of evaluable patients. On retrospective review, bone pain improved in 67% of evaluable patients, with a decrease in narcotic use in 56%. |
| Biomark Analysis: | Serum prostatespecific antigen levels were prospectively monitored as a biomarker for cancer activity. |
| Control Group Info: | placebo |
| Treatment Info: | Patients received 100 mg of cabozantinib daily. Those with stable disease per RECIST at 12 weeks were randomly assigned to cabozantinib or placebo. |
| Primary End Point: | objective response rate at 12 weeks and progression free survival (PFS) after random assignment. |
| Secondary End Point: | NA |
| Patients Number: | 171 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | The objective response rate at 12 weeks was 5%, with stable disease in 75% of patients. Thirtyone patients with stable disease at week 12 were randomly assigned. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | Median PFS was 23.9 weeks (95% CI, 10.7 to 62.4 weeks) with cabozantinib and 5.9 weeks (95% CI, 5.4 to 6.6 weeks) with placebo (hazard ratio, 0.12; P < .001). |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most common grade 3 adverse events were fatigue (16%), hypertension (12%), and handfoot syndrome (8%). |
| Conclusions: | Cabozantinib has clinical activity in men with CRPC, including reduction of soft tissue lesions, improvement in PFS, resolution of bone scans, and reductions in bone turnover markers, pain, and narcotic use. |