Entry Detail
| General information | |
| Database: | DB00560 |
| Objective: | This trial was designed to assess the efficacy and tolerability of sunitinib in patients with advanced, previously treated UC. |
| Authors: | Gallagher DJ, et al |
| Title: | Phase II study of sunitinib in patients with metastatic urothelial cancer. |
| Journal: | J Clin Oncol. |
| Year: | 2010 |
| PMID: | 20142593 |
| Trial Design | |
| Clinical Trial Id: | NA |
| 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: | Phase II Study |
| Key Patients Feature: | Patients with previously treated progressive metastatic UC of thebladder, renal pelvis, ureter, or urethra histologically confirmed at Memorial SloanKettering Cancer Center were eligible. Progressive disease wasdefined as new or progressing unidimensionally measurable lesions oncrosssectional imaging. Previously treated was defined as treatment with oneto four prior cytotoxic agents, administered in the perioperative or metastaticsetting. At least 4 weeks must have elapsed since radiotherapy or prior chemotherapy. Additional inclusion criteria included: Karnofsky performancescore (KPS) 60; age 18 years; total serum bilirubin 1.5; serum AST andserum ALT 2.5 upper limit of normal, or AST and ALT 5 ULN if liverfunction abnormalities are related to the underlying malignancy; absoluteneutrophil count 1, 000 cells/mm3; platelets more than 100, 000 cells/mm3;hemoglobin 8.0 g/dL; and creatinine 2.0 mg/dL. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | patients received sunitinib on one of two schedules (50 mg per day for 4 weeks on and 2 weeks off [cohort A], 37.5 mg per day continuously [cohort B]) |
| Primary End Point: | response rate and safety |
| Secondary End Point: | time to disease progression (TTP) and overall survival (OS). |
| Patients Number: | 77 |
| Trial Results | |
| DLT_MTD: | Therewas one treatmentrelated death, and 47 patients (33 cohort A, 24 cohort B) experienced grade 3or 4 toxicity. |
| Objective Response Rate: | Confirmed partial responses were seen in three patients(7%) in cohort A and one patient (3%) in cohort B (Table 2) and one patient remains on treatment with a PR lasting 24 months |
| Disease Control Rate: | NA |
| Median Time to Progression: | Tumor regression lasted between 0.6 and 23.4 months with 29% of patients achieving response lasting longer than 3 months. |
| Median PFS A vs. C: | 2.4 v 2.3 months; P=0 .4 |
| Median OS A vs. C: | 7.1 v 6.0 months; P=0.4 |
| Adverse Event(agent arm): | There was one treatmentrelated death, and 47 patients (33 cohort A, 24 cohort B) experienced grade 3 or 4 toxicity. Toxicities related to treatment that resulted in patients coming off treatment were fatigue, hypertension, acute coronary syndrome, urinary clot retention, and hematuria. |
| Conclusions: | Sunitinib did not achieve the predetermined threshold of or= 20% activity defined by Response Evaluation Criteria in Solid Tumors. Hotheyver, antitumor responses were observed, identifying the vascular endothelial growth factor axis as a viable pathway for UC treatment. The reported clinical benefit in previously treated patients warrants further investigation in a disease for which there is no US Food and Drug Administrationapproved treatment. |