Phase II study of pazopanib and weekly paclitaxel in metastatic or locally advanced squamous penile carcinoma patients previously treated with cisplatin-based chemotherapy: PAZOPEN study

Background: Metastatic or locally advanced squamous penile carcinoma (MLASPC) is an infrequent disease, with extremely bad prognosis. Platinum based chemotherapy is the most active treatment with a response rate (RR) of 30% and only 12 months of overall survival. New active agents are urgently needed. The combination of the antiangiogenic agent Pazopanib and paclitaxel have been tested in transitional carcinoma and melanoma with high number of responses and good tolerance profile. The aim of this study is to test the activity and safety of the combination in patients (pts) with MLASPC progressing to platinum based regimens. Methods: Phase II open label, single arm, multicentre study. Main inclusion criteria are: diagnosis of squamous penile carcinoma, ECOG 0-1, measurable disease by RECIST criteria, progressive disease after previous platinum based treatment, either in neoadyuvant, adyuvant or metastatic setting, adequate hepatic, renal and haematological function. Patients will receive treatment with pazopanib 800 mg p.o daily and paclitaxel 65 mg/m2/weekly D1, 8 and 15 every four weeks cycle. Main objective is RR (complete (CR) and partial response (PR) measured by RECIST criteria). Secondary objectives: Clinical benefit rate, (CR+ PR + SD), progression-free survival, response duration, overall survival, toxicity and tolerance profile. Whole exome sequencing will be performed to describe most frequent alterations in penile cancer. This is a two stage Simon optimal design for phase II trials. Considering an estimated 30% RR with P0 = 10%, (alpha error 5%, beta 20%), 10 patients will be included in first stage and if 2 or more responses are observed, then 19 additional patients will be included in second stage. If more than 5 responses are observed efficacy of treatment will be considered. The sample size, taking into account a 10% drop out rate will be 32 pts. Trial will be performed in 8 hospital centres of the SOGUG group. Study has been approved by ethic committees and health authorities.