Efficacy Assessment of Induction Carboplatin, Paclitaxel, and Pembrolizumab in Locoregionally Advanced Penile Cancer: A Phase 2 Clinical Study
- Trial ID
- 2023-506731-15-00
- Protocol
- N22APC
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this Phase 2 clinical study is to evaluate the **pathological complete response (pCR)** in patients with locoregionally advanced penile cancer following induction treatment with carboplatin, paclitaxel, and pembrolizumab. Achieving a pCR is clinically significant as it may correlate with improved long-term outcomes and survival rates in this patient population.
Secondary objectives include:
- Establishing the safety of pre-operative carboplatin, paclitaxel, and pembrolizumab (CP+P) treatment in penile cancer patients.
- Assessing the durability of clinical benefit after pre-operative CP+P treatment.
Participants
The clinical trial focuses on **locoregionally advanced penile cancer** and involves a study population exclusively composed of male participants aged 18 years and older. The trial does not include female subjects or vulnerable populations. Participants are required to have a histologically confirmed diagnosis of squamous cell carcinoma of the penis and must provide written informed consent. The trial population is selected based on specific disease stages, including cTxN2-3, cTxN1 with certain nodal characteristics, or resectable inguinal or pelvic lymph node recurrence, potentially in combination with oligometastatic disease. Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 and demonstrate adequate organ function. Lifestyle considerations such as diet and physical activity are not specified. The sponsor has not provided information regarding the total number of participants in the study.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy of a treatment regimen involving **carboplatin**, **paclitaxel**, and **pembrolizumab** for patients with locoregionally advanced penile cancer. This is a Phase 2, randomized, double-blind, controlled trial. The trial is expected to commence recruitment in June 2024 and conclude by June 2026, with an estimated duration of 52 weeks for each participant. The primary objective is to assess the pathological complete response (pCR) in all evaluable patients, while secondary endpoints include the evaluation of all-grade toxicity, treatment-related grade 3/4 toxicity, progression-free survival, and overall survival.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis, and disease stage. Following the screening, participants will receive the study treatment through **intravenous infusion**. Regular follow-up visits will be scheduled to monitor the participants' response to treatment and any adverse effects. The end-of-study visit will occur at the conclusion of the treatment period, where final assessments will be conducted to evaluate the primary and secondary endpoints.
Participant involvement is expected to last for the entire 52-week treatment period unless conditions arise that necessitate early termination. Such conditions may include significant adverse reactions, disease progression, or withdrawal of consent. The trial will adhere to rigorous ethical standards, ensuring that all participants provide informed consent and that their health and safety are prioritized throughout the study.
Treatment
The clinical trial involves the administration of **Carboplatin**, marketed as Carboplatine Fresenius Kabi 10 mg/mL concentrate for solution for infusion. This experimental medication is provided in the form of a **solution for infusion** and is administered via the **intravenous** route. The maximum daily dose is 750 mg, with a total maximum dose of 2250 mg over a treatment period of up to 9 weeks. The active substance, carboplatin, is of chemical origin and is classified under the ATC code L01XA02. Participant compliance with the dosing schedule will be monitored throughout the trial.
**Pembrolizumab**, marketed as KEYTRUDA 25 mg/mL concentrate for solution for infusion, is another experimental medication used in this study. It is also provided as a **solution for infusion** and administered through **intravenous infusion**. The maximum daily dose is 400 mg, with a total maximum dose of 3600 mg over a treatment period of up to 52 weeks. Pembrolizumab is a protein-based substance, specifically classified under the ATC code L01FF02. The administration schedule and participant adherence will be closely monitored to ensure compliance.
The trial also includes the administration of **Paclitaxel**, marketed as Paclitaxel Fresenius Kabi 6 mg/mL concentrate for solution for infusion. This medication is provided as a **solution for infusion** and administered via the **intravenous** route. The maximum daily dose is 420 mg/m², with a total maximum dose of 1260 mg/m² over a treatment period of up to 9 weeks. Paclitaxel is of chemical origin and is classified under the ATC code L01CD01. Participant compliance with the dosing regimen will be monitored throughout the study.
No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified in this clinical trial. The focus is on evaluating the efficacy of the combination of these experimental medications in achieving a pathological complete response in patients with locoregionally advanced penile cancer.
Efficacy
The efficacy of the clinical trial will be assessed primarily through the evaluation of **pathological complete response (pCR)** in all patients who are evaluable for response. This primary endpoint will determine the effectiveness of the treatment regimen consisting of induction carboplatin/paclitaxel combined with pembrolizumab for patients with locoregionally advanced penile cancer. The secondary endpoints include the assessment of all-grade toxicity and treatment-related grade 3/4 toxicity as per the NCI-CTC-V5 criteria, progression-free survival (PFS), and overall survival (OS). PFS and OS will be measured from day 1 of study therapy in all patients who were registered for the study and started treatment. These survival metrics will be analyzed using Kaplan-Meier curves, and median PFS or OS, as well as PFS or OS at fixed time points (e.g., 1, 2, or 3 years), may be reported.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Male patients of more than 18 years of age
- Histologically confirmed diagnosis of squamous cell carcinoma of the penis
- The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
- 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 as defined in the protocol. Specimens must be collected within 14 days prior to the start of study intervention.
Exclusion Criteria
- 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
- 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. Note: please refer to Section 5.5.2 for information on COVID-19 vaccines
- 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.
- 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.
- 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.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- 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.
- Has had an allogenic tissue/solid organ transplant.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Yet Recruiting | 01 Jun 2024 | 5 |
 The Netherlands | Recruiting | 01 Jun 2024 | — |
| Netherlands | — | — | 27 |
Sites & Investigators
Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Paclitaxel Fresenius Kabi 6 mg/ml concentraat voor oplossing voor infusie | Other | CONCENTRAAT VOOR OPLOSSING VOOR INFUSIE | INTRAVENOUS | 420 | 9 | PRD409125 |
Carboplatine Fresenius Kabi 10 mg/ml concentraat voor oplossing voor infusie | Other | CONCENTRAAT VOOR OPLOSSING VOOR INFUSIE | INTRAVENOUS | 750 | 9 | PRD669111 |
KEYTRUDA 25 mg/mL concentrate for solution for infusion | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENIOUS INFUSION | 400 | 52 | PRD4323105 |