Carboplatin/Paclitaxel + Pembrolizumab for Locoregionally Advanced Penile Cancer

NCT06353906 | Recruiting Phase 2

• 1 other identifier: N22APC
• Study Type: interventional
• Target: 27
• Locations: 2 countries
• Sites: 2

Brief Summary

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

Conditions

Urologic Neoplasms; Urogenital Neoplasms; Male Urogenital Diseases; Penile Cancer; Penile Squamous Cell Carcinoma; Locally Advanced Penile Carcinoma

Outcome Measures

Primary Outcomes (1)

• Pathological complete response (pCR)

  Pathological complete response defined as pT0N0 in all evaluable patients

  Immediately after surgery

Secondary Outcomes (7)

• Drug toxicity

  Drug-related serious adverse events will be noted from day of registration until 90 days after the last protocol treatment/administration.

• Progression-free survival (PFS)

  Through study completion, at a minimum of 24 months

• Overall survival (OS)

  Through study completion, at a minimum of 24 months

• Assessment of correlation between clinical endpoints and tumor characteristics

  Tumor tissue will be collected at baseline and during resection procedure. Clinical endpoints of pCR, PFS and OS will be determined as mentioned above

• Tumor tissue HPV status in relation to treatment response

  12 weeks after last patient first visit

Study Arms (1)

Induction chemo-immunotherapy combination followed by consolidative surgical resection

EXPERIMENTAL

Patients receive three cycles of induction carboplatin+paclitaxel on days 1, 22 and 43, with two concurrent cycles of fixed-dose pembrolizumab on days 1 and 43. Within 3-9 weeks after the last cycle of induction chemo-immunotherapy, patients undergo complete resection of remaining tumor tissue. Patients start subsequent adjuvant immunotherapy with fixed-dose pembrolizumab for up to seven 6-week cycles between 3-9 weeks after surgery.

Drug: Carboplatin/Paclitaxel; Drug: Pembrolizumab; Procedure: Partial or total penectomy with inguinal and/or pelvic lymph node dissection

Interventions

Carboplatin/Paclitaxel DRUG

Induction: three cycles of intravenous carboplatin AUC5 (max 750 mg) and paclitaxel 175 mg/m2, during cycle 1, 2 and 3 (day 1, 22, 43)

Also known as: CarboTaxol, PC

Induction chemo-immunotherapy combination followed by consolidative surgical resection

Pembrolizumab DRUG

Induction: 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

Also known as: Keytruda

Induction chemo-immunotherapy combination followed by consolidative surgical resection

Partial or total penectomy with inguinal and/or pelvic lymph node dissection PROCEDURE

Resection of part or all of the penis with complete removal of suspect lymphnodes in the inguinal and/or pelvic area

Also known as: Inguinal lymphadenectomy; groin dissection, PLND

Induction chemo-immunotherapy combination followed by consolidative surgical resection

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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
• 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.
• 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.
• 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.
• 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.
• Have adequate organ function defined as: absolute neutrophil count (ANC) ≥1.5 10e9 /L, platelets ≥100 10e9/L; hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L; creatinine ≤1.5 × ULN OR GFR\>30 ml/min as per Cockcroft-Gault formula in patients with creatinine levels \> 1.5x institutional ULN; total bilirubin 1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5 × ULN; AST (SGOT) and ALT (SGPT) ≤2.5 × ULN; International normalized ratio (INR), prothrombin time (PT) OR activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants. Specimens must be collected within 14 days prior to the start of study intervention.

You may not qualify if:

• 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.
• 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.
• 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.
• Has known active or treated CNS metastases and/or carcinomatous meningitis.
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
• 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.
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• Has an active infection requiring systemic therapy.
• Has a known history of Human Immunodeficiency Virus (HIV) infection.
• 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.
• Has not adequately recovered from major surgery or has ongoing surgical complications.

Sponsors & Collaborators

• The Netherlands Cancer Institute: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (2)

UZ Leuven

Leuven, 3000, Belgium

RECRUITING

NKI-AVL

Amsterdam, North Holland, 1066CX, Netherlands

RECRUITING

MeSH Terms

Conditions

Urologic Neoplasms; Urogenital Neoplasms; Male Urogenital Diseases; Penile Neoplasms

Interventions

CP protocol; pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urologic Diseases; Genital Neoplasms, Male; Genital Diseases, Male; Genital Diseases; Penile Diseases

Study Officials

• Michiel S. van der Heijden, PhD

  The Netherlands Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michiel S. van der Heijden, PhD

CONTACT

+31205129111; ms.vd.heijden@nki.nl

Jan-Jaap J. Mellema, MD

CONTACT

+31205129111; j.mellema@nki.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2024
• First Posted: April 9, 2024
• Study Start: August 13, 2024
• Primary Completion (Estimated): October 14, 2026
• Study Completion (Estimated): January 14, 2028
• Last Updated: December 8, 2025

Record last verified: 2025-09

Locations

NL (1); BE (1)