Expression of androgen receptors (AR), is reported in more than 80% of salivary duct carcinomas (SDC) and in 50% of adenocarcinomas, NOS. Similary to prostate cancer (Pca), androgen deprivation therapy (ADT) has been employed with success in patients with metastatic AR-expressing SDC and adenocarcinoma, NOS in so much as an international randomized trial is ongoing to assess the efficacy of ADT over chemotherapy as first line treatment in this setting of patients (NCT01969578). Abiraterone acetate was approved in advanced, castration resistant Pca in 2011. We tested the activity of abiraterone in two patients with AR-positive castration resistant adenocarcinoma, NOS obtaining two partial responses (Locati LD, Cancer Biol Ther 2014).
This is a phase II trial (NCT02867852) aimed at assessing the activity (CR+ PR) of abiraterone in castration resistant AR-positive SGCs. The drug will be considered effective and worth of further evaluation if the response rate will be at least 20%. The null hypothesis will be RR 5% versus the alternative RR20%. A 2-stage Simon design will be applied. Type I and type II error rates are set at the 10% and 20% levels. If at least 1/9 response will be observed in the first step, patients’ enrolment will go on up to a final overall sample size of 24 subjects. If at least 3/24 responses will be recorded, the null hypothesis will be rejected in favor of the alternative and the drug considered promising and worthy of further investigation. Objective tumor response and time to progression will be measured according to RECIST criteria 1.1 and to PCWG2 recommendations for bone lesions. Twenty four patients with AR-expressing SGC, progressed on ADT, will be enrolled over two years. Four 250 mg tablets of abiraterone acetate will be administered daily to patients until progression of disease or intolerable toxicity. Disease control rate, incidence of adverse events, overall survival and progression free survival will be assessed as well. Tumor samples will be also collected for translational analyses (e.g. CYP17 expression; PI3K mutations). Blood and saliva samples will be collected as well.
Clinical trial identification
Legal entity responsible for the study
Fondazione IRCCS Istituto Nazionale dei Tumori Milan, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
All authors have declared no conflicts of interest.