Entry Detail
| General information | |
| Database: | DB00564 |
| Objective: | There is no effective secondline systemic chemotherapy for patients with disease progression after cisplatinbased chemotherapy. a phase 2 trial of sorafenib was performed to determine the activity and toxicity of this agent in a multiinstitutional setting in patients previously treated with 1 prior chemotherapy regimen. |
| Authors: | Dreicer R, et al |
| Title: | Phase 2 trial of sorafenib in patients with advanced urothelial cancer: a trial of the Eastern Cooperative Oncology Group. |
| Journal: | cancer |
| Year: | 2009 |
| PMID: | 19536901 |
| Trial Design | |
| Clinical Trial Id: | NA |
| Agent: | sorafenib |
| Target: | Vascular endothelial growth factor receptor 1 BRaf protooncogene serine/threonineprotein kinase Protooncogene tyrosineprotein kinase receptor ret |
| Cancer Type: | Urothelial Carcinoma |
| Cancer Subtype: | transitional cell carcinoma of the urothelium |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | Phase II Trial |
| Key Patients Feature: | Eligible patients had histologically confirmed transitionalcell carcinoma (or mixed histologies containing a component of transitional cell carcinoma) of the urotheliumwith evidence of progressive, bidimensionally measurableregional or metastatic disease. Patients must have beendiseasefree from prior malignancies for at least 5 years, with an Eastern Cooperative Oncology Group (ECOG)performance status of 0 to 1 at entry. Patients must havedemonstrated progressive disease after 1 and only 1 priorsystemic chemotherapy regimen administered in the metastatic setting. Prior perioperative therapy in either the neoadjuvant or adjuvant setting was permitted, providedthat it was completed >12 months before the chemotherapy administered in the metastatic setting. Patients musthave been at least 4 weeks out from major surgery.Adequate renal and hepatic function were required, with aserum creatinine <1.5 mg/dL, aspartate aminotransferase(AST) 2.5 mg/dL, and bilirubin 1.5 times the upperlimit of normal. Adequate bone marrow reserve was mandated with a requirement for neutrophils 1500 mm3and a platelet count 100, 000/lL at entry. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | pts were treated with sorafenib 400 mg orally twice daily continuously until progression or unacceptable toxicity |
| Primary End Point: | 4month PFS rate |
| Secondary End Point: | NA |
| Patients Number: | 27 |
| Trial Results | |
| DLT_MTD: | There were no therapyrelated deaths, andcommon grade 3 toxicities included fatigue and handfoot syndrome. |
| Objective Response Rate: | There were no objective responses observed The 4month progression free survival (PFS) rate was 9.5%; median overall survival of the group was 6.8 months |
| Disease Control Rate: | 0.55 |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 2.2 months (90% CI, 1.83.7 months) |
| Median OS A vs. C: | 6.8 months (90% CI, 5.7 8.5 months) |
| Adverse Event(agent arm): | There were no therapyrelated deaths, and common grade 3 toxicities included fatigue and handfoot syndrome. |
| Conclusions: | Although sorafenib as a single agent has minimal activity in patients with advanced urothelial cancer in the secondline setting, further investigation of tyrosine kinase inhibitors using different trial designs with PFS endpoints is warranted. |