TheraP: a randomized phase 2 trial of ¹⁷⁷Lu‐<scp>PSMA</scp>‐617 theranostic treatment vs cabazitaxel in progressive metastatic castration‐resistant prostate cancer (Clinical Trial Protocol <scp>ANZUP</scp> 1603)

<jats:sec><jats:title>Objective</jats:title><jats:p>To assess the activity and safety of cabazitaxel chemotherapy vs that of treatment with <jats:sup>177</jats:sup>Lu‐<jats:styled-content style="fixed-case">PSMA</jats:styled-content>‐617, a novel radiolabelled small molecule that binds with high affinity to prostate‐specific membrane antigen (<jats:styled-content style="fixed-case">PSMA</jats:styled-content>), in men with metastatic castration‐resistant prostate cancer (<jats:styled-content style="fixed-case">mCRPC</jats:styled-content>) who have received prior docetaxel treatment.</jats:p></jats:sec><jats:sec><jats:title>Patients and methods</jats:title><jats:p>The TheraP trial (<jats:styled-content style="fixed-case">ANZUP</jats:styled-content> 1603) is an open‐label, randomized, stratified, two‐arm multicentre phase 2 trial comparing the activity and safety of cabazitaxel chemotherapy vs <jats:sup>177</jats:sup>Lu‐<jats:styled-content style="fixed-case">PSMA</jats:styled-content>‐617 therapy in the treatment of men with <jats:styled-content style="fixed-case">mCRPC</jats:styled-content>. Key eligibility criteria include prior docetaxel chemotherapy, rising prostate‐specific antigen (<jats:styled-content style="fixed-case">PSA</jats:styled-content>) level, sufficient <jats:styled-content style="fixed-case">PSMA</jats:styled-content> avidity, as defined by centrally reviewed <jats:sup>68</jats:sup>Ga‐<jats:styled-content style="fixed-case">PSMA</jats:styled-content>‐11 and fluorodeoxyglucose (<jats:styled-content style="fixed-case">FDG</jats:styled-content>)‐positron emission tomography (<jats:styled-content style="fixed-case">PET</jats:styled-content>)/computed tomography (<jats:styled-content style="fixed-case">CT</jats:styled-content>) with no discordant <jats:styled-content style="fixed-case">FDG</jats:styled-content>‐avid <jats:styled-content style="fixed-case">PSMA</jats:styled-content>‐negative sites of disease. Patients in the control group receive standard treatment with cabazitaxel (20 mg/m<jats:sup>2</jats:sup>) i.v. every 3 weeks with prednisolone 10 mg daily orally, for a maximum of 10 cycles. Patients in the experimental group receive <jats:sup>177</jats:sup>Lu‐<jats:styled-content style="fixed-case">PSMA</jats:styled-content>‐617 (8.5 <jats:styled-content style="fixed-case">GB</jats:styled-content>q decreasing by 0.5 <jats:styled-content style="fixed-case">GB</jats:styled-content>q per cycle) i.v. every 6 weeks, for up to a maximum of six cycles. In the event of an exceptional response as defined on centrally reviewed post‐therapy single‐photon emission <jats:styled-content style="fixed-case">CT</jats:styled-content> imaging, treatment will be suspended but can recommence on progression. The trial aims to include 200 patients who will be centrally randomized to one of the two treatment groups, in a 1:1 ratio. The primary endpoint is <jats:styled-content style="fixed-case">PSA</jats:styled-content> response. Secondary endpoints are overall survival, progression‐free survival (<jats:styled-content style="fixed-case">PFS</jats:styled-content>), radiographic <jats:styled-content style="fixed-case">PFS</jats:styled-content>,<jats:styled-content style="fixed-case"> PSA PFS</jats:styled-content>, objective tumour response, pain response, pain <jats:styled-content style="fixed-case">PFS</jats:styled-content>, health‐related quality of life, and frequency and severity of adverse events. The treatment and outcomes of patients excluded on the basis of low <jats:styled-content style="fixed-case">PSMA</jats:styled-content> avidity or discordant <jats:styled-content style="fixed-case">FDG</jats:styled-content>‐avid disease on screening <jats:sup>68</jats:sup>Ga‐<jats:styled-content style="fixed-case">PSMA</jats:styled-content>‐11 and Fluorine‐18 (<jats:sup>18</jats:sup>F)‐<jats:styled-content style="fixed-case">FDG</jats:styled-content>‐<jats:styled-content style="fixed-case">PET</jats:styled-content>/<jats:styled-content style="fixed-case">CT</jats:styled-content> scan will also be assessed. Enrolment in the study commenced on 29 January 2018.</jats:p></jats:sec><jats:sec><jats:title>Results and Conclusions</jats:title><jats:p><jats:sup>177</jats:sup>Lu‐<jats:styled-content style="fixed-case">PSMA</jats:styled-content>‐617 offers a potential additional life‐prolonging treatment option for men with <jats:styled-content style="fixed-case">mCRPC</jats:styled-content>. The results of this trial will determine, for the first time in a randomized design, the activity and safety of <jats:sup>177</jats:sup>Lu‐<jats:styled-content style="fixed-case">PSMA</jats:styled-content>‐617, as compared with cabazitaxel chemotherapy in men with progressive <jats:styled-content style="fixed-case">mCRPC</jats:styled-content>.</jats:p></jats:sec>