This is a single-armed, single-centre, non-blinded phase II trial to assess efficacy of induction chemo-immunotherapy for resectable node-positive squamous cell carcinoma of the penis
The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
Histologically confirmed diagnosis of squamous cell carcinoma of the penis.
cTxN2-3 or
cTxN1 in case of central nodal necrosis and/or an irregular nodal border, or node >3cm, or
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
Has received prior systemic anti-cancer therapy including investigational agents, or an investigational device, within 4 weeks prior to registration.
Has received prior radiotherapy within 4 weeks of start of study intervention or radiation-related toxicities requiring corticosteroids.
Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
Single group
Carboplatin/Paclitaxel
DrugInduction: three cycles of intravenous carboplatin AUC5 (max 750 mg) and paclitaxel 175 mg/m2, during cycle 1, 2 and 3 (day 1, 22, 43)
Pembrolizumab
DrugInduction: two cycles of intravenous pembrolizumab 400 mg during cycle 1 and 3 (day 1 and 43) Adjuvant: up to seven cycles of fixed-dose intravenous pembrolizumab 400 mg, on day 1 every 6 weeks within 3-9 weeks after surgery
Partial or total penectomy with inguinal and/or pelvic lymph node dissection
Procedure/SurgeryResection of part or all of the penis with complete removal of suspect lymphnodes in the inguinal and/or pelvic area
Pathological complete response (pCR)
Pathological complete response defined as pT0N0 in all evaluable patients
Drug toxicity
Safety in terms of chemotherapy and immunotherapy-related adverse events of grade 3 or higher according to version 5.0 of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) criteria.
Progression-free survival (PFS)
PFS is defined as time from start of therapy until an event. Events include: * Histologically or cytologically established recurrence after surgery * Omission of surgery as a result of progressive disease. * Unequivocal radiological progression. In case of equivocal results, radiological evaluation may continue. When unequivocal progression is established, the event date will be the first tumor assessment where new lesions were noted. * Switch to another systemic therapy. Note: in case a radiologically responding patient refuses surgery and elects other locoregional therapy (e.g. (chemo)radiotherapy), this is not considered a progression event. PFS will be estimated using the Kaplan-Meier method. The median PFS and 95% confidence interval will be reported.
Overall survival (OS)
OS is defined as the time between the date of enrollment and the date of death. OS will be estimated using the Kaplan-Meier method. The median OS and 95% confidence interval will be reported.
Assessment of correlation between clinical endpoints and tumor characteristics
Tumor tissue gathered from patients at baseline via biopsy and, in case of non complete response, at surgery will be tested via a comprehensive analysis of the tumor microenvironment (TME) using state of the art multiparameter techniques to determine the TME composition and activation status in responders vs non-responders. Additional analyses on clinical endpoints (i.e. pCR, PFS and OS) will be carried out between patient groups defined by tumor characteristics.
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The Netherlands Cancer Institute
Lead sponsor
Merck Sharp & Dohme LLC
Collaborator
