Entry Detail
| General information | |
| Database: | DB00557 |
| Objective: | Angiogenesis contributes to the progression of urothelial carcinoma (UC). In the current study, the authors investigated the role of maintenance sunitinib in patients with advanced UC. |
| Authors: | Grivas PD, et al |
| Title: | Doubleblind, randomized, phase 2 trial of maintenance sunitinib versus placebo after response to chemotherapy in patients with advanced urothelial carcinoma. |
| Journal: | cancer |
| Year: | 2014 |
| PMID: | 24249435 |
| Trial Design | |
| Clinical Trial Id: | NCT00393796 |
| Agent: | sunitinib |
| Target: | FL cytokine receptor Mast/stem cell growth factor receptor Vascular endothelial growth factor receptor 2 Plateletderived growth factor receptor |
| Cancer Type: | Urothelial Carcinoma |
| Cancer Subtype: | advanced urothelial carcinoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | DoubleBlind, Randomized, phase II Trial |
| Key Patients Feature: | Eligible patients had a pathologic diagnosis of UC (pureor mixed histology); an Eastern Cooperative OncologyGroup performance status (ECOG PS) of 0 to 2; a lifeexpectancy >6 months; adequate hematologic, renal, hepatic, and cardiovascular function; and had achieved SDor a partial (PR) or complete (CR) response after 4 to 6cycles of standard firstline chemotherapy for locallyrecurrent or metastatic UC. Prior adjuvant or neoadjuvant chemotherapy was allowed, but no prior antiangiogenic agents were permitted for the current disease stage. |
| Biomarker: | serum vascular endothelial growth factor (VEGF)/soluble VEGF receptor2 (sVEGFR2) |
| Biomark Analysis: | Patients receiving placebo were found to have no changes in their serum VEGF/sVEGFR2 levels over time. Patients treated with sunitinib had no significant change in their VEGF level, but the sVEGFR2 level significantly decreased after cycles 1 and 2 (P < .0001) and at the time of disease progression (P = .0002). A baseline VEGF level that was at or greater than the median was found to be correlated with a longer PFS. |
| Control Group Info: | sunitinib versus placebo |
| Treatment Info: | pts were randomized to sunitinib at a dose of 50 mg/day (28 days on and 14 days off) or placebo. |
| Primary End Point: | the 6month progression rate |
| Secondary End Point: | safety, survival, change in serum vascular endothelial growth factor (VEGF)/soluble VEGF receptor2 (sVEGFR2), and the activity of sunitinib |
| Patients Number: | 54 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | Sixteen patients who were receiving placebo received sunitinib at the time of disease progression, with the best responses being 1 partial response (6.3%), 6 cases of stable disease (37.5%), and 5 cases of progressive disease (31.3%); 4 patients were not evaluable for response. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 2.9 months (range, 0.5 months32.5 months) versus 2.7 months (range, 0.8 months 265 months) for the sunitinib versus placebo arms, respectively. |
| Median OS A vs. C: | 10.5 months for sunitinib (95% CI, 8.1 months13.8 months) versus 10.3 months for placebo (95% CI, 6.8 months18.1 months) |
| Adverse Event(agent arm): | The most common grade 3 to 4 adverse events (graded according to version 3.0 of the National Cancer Institute Common Terminology Criteria for Adverse Events) among patients receiving sunitinib were thrombocytopenia, diarrhea, mucositis, fatigue, and hypertension. There were no grade 3 or 4 adverse events noted among > 5% of patientsreceiving placebo. |
| Conclusions: | The current multicenter study was limited by premature closure and a small sample size. Maintenance sunitinib did not appear to improve the 6month progression rate. Openlabel sunitinib was found to have only modest activity. The sVEGFR2 level decreased among patients receiving sunitinib. |