PEMBROLIZUMAB for Locoregionally advanced penile cancer

Inclusion criteria

• {"criterion_text":"- Male patients of more than 18 years of age"}
• {"criterion_text":"- Histologically confirmed diagnosis of squamous cell carcinoma of the penis"}
• {"criterion_text":"- The participant (or legally acceptable representative if applicable) provides written informed consent for the trial."}
• {"criterion_text":"- Patients have one of the following disease stages: - cTxN2-3 or - cTxN1 in case of central nodal necrosis and/or an irregular nodal border, or node >3cm, or \t- Inguinal or pelvic lymph node recurrence that is potentially resectable. Any of the disease stages above, in combination with oligometastatic disease with a maximum of 2 distant metastases is allowed, as long as these metastases can be treated by resection or radiotherapy. This should be established in the multidisciplinary tumor board before enrolment."}
• {"criterion_text":"- Archival tumor tissue sample or newly obtained [core, incisional or excisional] biopsy of a tumor lesion not previously irradiated has been provided. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue."}
• {"criterion_text":"- A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 180 days after the last dose of study treatment and refrain from donating sperm during this period."}
• {"criterion_text":"- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 14 days prior to the first dose of study intervention."}
• {"criterion_text":"- Have adequate organ function as defined in the protocol. Specimens must be collected within 14 days prior to the start of study intervention."}

Exclusion criteria

• {"criterion_text":"- 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"}
• {"criterion_text":"- Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease."}
• {"criterion_text":"- Has an active infection requiring systemic therapy."}
• {"criterion_text":"- Has a known history of Human Immunodeficiency Virus (HIV) infection."}
• {"criterion_text":"- Concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV DNA) and/or Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection. Hepatitis B and C screening tests are not required unless a patient has a known history of HBV or HCV infection. Participants must have completed curative anti-viral therapy at least 6 months prior to randomization."}
• {"criterion_text":"- Has not adequately recovered from major surgery or has ongoing surgical complications."}
• {"criterion_text":"- Major pelvic surgical procedure within 4 weeks prior to enrolment or anticipation of need for a major surgical procedure during the course of the study other than for the disease under study."}
• {"criterion_text":"- Has a history or current evidence of any condition, therapy, or laboratory abnormality or other circumstance that might confound the results of the study, interfere with the participant’s participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator."}
• {"criterion_text":"- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial."}
• {"criterion_text":"- Is expecting to father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment."}
• {"criterion_text":"- Has had an allogenic tissue/solid organ transplant."}
• {"criterion_text":"- Has received prior systemic anti-cancer therapy including investigational agents, or an investigational device, within 4 weeks prior to registration"}
• {"criterion_text":"- Has received prior radiotherapy within 4 weeks of start of study intervention or radiation-related toxicities requiring corticosteroids"}
• {"criterion_text":"- 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. Note: please refer to Section 5.5.2 for information on COVID-19 vaccines"}
• {"criterion_text":"- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug."}
• {"criterion_text":"- Known additional malignancy that is progressing or has required active treatment within the past 3 years. Exceptions: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded. Patients with low-risk prostate cancer (defined as Stage T1/T2a, Gleason score ≤ 6, and PSA ≤ 10 ng/mL) who are treatment-naive and undergoing active surveillance are eligible."}
• {"criterion_text":"- Has known active or treated CNS metastases and/or carcinomatous meningitis."}
• {"criterion_text":"- Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients."}
• {"criterion_text":"- Has active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid). Patients with vitiligo, psoriasis or other mild skin disease can still be included."}

Primary endpoints

• {"endpoint_text":"- Efficacy, defined as pathological complete response (pCR) in all patients who are evaluable for response","definition_or_measurement_approach":"Defined as pathological complete response (pCR) in all patients who are evaluable for response."}

Secondary endpoints

• {"endpoint_text":"- All-grade toxicity and treatment-related grade 3/4 toxicity by NCI-CTC-V5 will be reported in all patients who received at least one cycle of treatment","definition_or_measurement_approach":"Toxicity will be reported using NCI-CTC-V5 in all patients who received at least one cycle of treatment."}
• {"endpoint_text":"- Progression-free survival, measured from day 1 of study therapy in all patients who were registered for the study and started treatment. \tOverall survival, measured from day 1 of study therapy, in all patients who were registered for the study and started treatment.","definition_or_measurement_approach":"Progression-free survival (PFS) and overall survival (OS) measured from day 1 of study therapy in all registered patients who started treatment."}
• {"endpoint_text":"- Overall survival, measured from day 1 of study therapy, in all patients who were registered for the study and started treatment.","definition_or_measurement_approach":"Overall survival (OS) measured from day 1 of study therapy in all registered patients who started treatment."}
• {"endpoint_text":"- PFS and OS will be assessed at the primary analysis and at any later time point. Survival data will be reported as Kaplan-Meier curves. Additionally, median PFS or OS and PFS or OS at fixed time points (eg 1,2 or 3 years) may be reported.","definition_or_measurement_approach":"PFS and OS assessed at primary analysis and later time points; survival reported as Kaplan-Meier curves; median PFS/OS and fixed-timepoint estimates (eg 1, 2, 3 years) may be reported."}

Netherlands

Earliest CTIS Part Ii Submission Date

10-04-2024

Latest Decision Or Authorization Date

14-11-2025

Processing Time Days

583

Number Of Sites

1

Number Of Participants

27

Belgium

Earliest CTIS Part Ii Submission Date

08-04-2025

Latest Decision Or Authorization Date

14-11-2025

Processing Time Days

220

Number Of Sites

1

Number Of Participants

5

Primary sponsor

Full Name

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands