Status:
Recruiting
Clinicaltrials.gov identifier:
Sponsor:
UNICANCER
Enrollment:
41
Study Design:
This is a phase 2 open label European multi-site study enrolling patients with metastatic collecting duct or medullary carcinoma which is histologically confirmed, who are treatment naïve in the metastatic setting, > 18 years of age, and with adequate end organ function. Once enrolled, patients receive gemcitabine plus a platinum salt plus bevacizumab. If patients achieve disease control on this regimen, with either stable disease or a partial or complete response, then treatment is continued with bevacizumab monotherapy until progression.
Rationale:
Though there is increasing awareness of the heterogeneity of RCC, collecting duct carcinoma has long been recognized as a separate entity, amounting to <1% of all kidney cancers. This subtype has been noted because of its aggressive behavior, and low likelihood of responding to conventional RCC regimens. Platinum-based chemotherapy has typically been used, extrapolating largely from treatment of urothelial carcinoma. As such, and on the basis of a preceding Phase I trial, a Phase II trial is evaluating the combination of gemcitabine, platinum agent, and bevacizumab in patients with metastatic collecting duct carcinoma.
Endpoints:
The primary outcome of the trial is a composite endpoint of objective response rate (RR) and progression-free survival (PFS) rate at 6 months. Secondary endpoints include PFS, overall survival (OS), and toxicity.
Comments:
This study is noteworthy in that collecting duct kidney cancer is rare, aggressive and has only been studied in a limited manner in clinical trials. Typically these patients are excluded from trials evaluating regimens for mRCC, or are enrolled in too small numbers to derive any conclusions. Given the similarities collecting duct kidney cancer shares histopathologically with urothelial carcinoma, the use of platinum-based chemotherapy is rational. On the other hand, the study is permitting enrollment of patients with medullary RCC. Though this subtype has some overlapping features with collecting duct kidney cancer, it is a distinct entity. For example, while it does also confer a poor prognosis with an aggressive phenotype, medullary RCC occurs more frequently in patients with sickle cell disease and is characterized by loss of INI1 expression. Thus, there could be some potential confounding with enrollment of both subtypes into this trial. Nevertheless, it is commendable to evaluate this rare subset of patients with platinum-based chemotherapy. Immune checkpoint inhibitors, having now demonstrated efficacy in both urothelial and renal cell carcinomas, are being studied in patients with non-clear cell RCC as a broad category, which will also provide additional information about new potential approaches towards these aggressive subtypes.
