| General information |
| Database: | DB00551 |
| Objective: | Thisphase II study assessed the safety and efficacy of everolimus, an oral mammalian target of rapamycin inhibitor in advanced transitional carcinoma cell (TCC) after failure of platinumbased therapy. |
| Authors: | Seront E, et al |
| Title: | Phase II study of everolimus in patients with locally advanced or metastatic transitional cell carcinoma of the urothelial tract: clinical activity, molecular response, and biomarkers |
| Journal: | Ann Oncol. |
| Year: | 2012 |
| PMID: | 22473592 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | everolimus
|
| Target: | Serine/threonineprotein kinase mTOR
|
| Cancer Type: | Urothelial Carcinoma |
| Cancer Subtype: | advanced transitional cell carcinoma of the urothelial tract |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | phase II study |
| Key Patients Feature: | Eligible patients were required to have histologically or cytologicallyconfirmed locally advanced or metastatic TCC, documented progressionafter firstline platinumbased chemotherapy (in neoadjuvant/adjuvantsetting or for distant metastases), disease not amenable to curativetreatment, at least one measurable lesion according to RECIST, and anEastern Cooperative Oncology Group performance status of zero to two.An interval of at least 4 weeks since the last cytotoxic chemotherapy, biological therapy, surgery, or radiotherapy was required. Patients wererequired to have an absolute neutrophil count >1500/¦Ìl, hemoglobin >9 g/dl, platelet count >100 000/¦Ìl, serum creatinine <1.5 ¡Á the upper limit ofnormal (ULN), total bilirubin <1.5 ULN, alanine aminotransferase (ALT)and aspartate aminotransferase (AST) <2.5 ULN, fasting cholesterol <300mg/dl, and fasting triglycerides <2.5 ULN. |
| Biomarker: | Angiogenesisrelated proteins ;PTEN expression and PIK3CA mutations |
| Biomark Analysis: | Angiogenesisrelated proteins were detected in plasma and changes during everolimus treatment were analyzed. PTEN expression and PIK3CA mutations were correlated to disease control. |
| Control Group Info: | single arm |
| Treatment Info: | patients with advanced TCC received everolimus 10 mg/day until progressive disease (PD) or unacceptable toxicity |
| Primary End Point: | the disease control rate (DCR), defined as either stable disease (SD), partial response (PR), or complete response at 8 weeks. |
| Secondary End Point: | NA |
| Patients Number: | 37 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | Two confirmed PR and eight SD were observed, resulting in a DCR of 27% at 8 weeks. |
| Disease Control Rate: | 0.27 |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 61 days [95% confidence interval (CI) 49-63 days; range, 17 -491days] |
| Median OS A vs. C: | 101 days (95% CI 82-128 days; range, 17-571 days) |
| Adverse Event(agent arm): | The most frequent grade 1-2 toxic effects were anemia (86%), nausea and vomiting (81%), and fatigue (64%). The main grade 3-4 toxic effects were fatigue (27%) and thrombocytopenia (13%). they observed two grade 5 adverse events: a cerebral bleed and a cardiac infarction not related to everolimus according to the investigators. |
| Conclusions: | Everolimus showed clinical activity in advanced TCC. The profile of the plasma angiogenesisrelated proteins suggested a role of the everolimus antiangiogenic properties in disease control. PTEN loss might be associated with everolimus resistance. |