Comparison of different treatment methods for muscle-invasive bladder cancer

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    What is this study about?

    This trial is designed for patients with muscle-invasive bladder cancer who are either unable to use or decline the use of cisplatin – a commonly used chemotherapy drug. The trial evaluates two treatment methods: surgery alone (cystectomy), and surgery combined with the medications pembrolizumab and/or enfortumab vedotin. The combination therapies happen before and after the surgery. The primary aim is to compare the event-free survival (EFS), meaning time without disease progression or death, in these different approaches. It’s important for potential participants to know they will be randomly assigned a method of treatment for comparison. Medical exams and tests will be conducted to ensure patient safety and monitor progress.

    Learn more about this Trial

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      Locations

      Where does the clinical trial take place?

      Bruxelles , Belgium

      Gent , Belgium

      Brugge , Belgium

      Roeselare , Belgium

      Herlev , Denmark

      Kobenhavn , Denmark

      Aarhus , Denmark

      Odense , Denmark

      Marseille , France

      Caen , France

      Nimes , France

      Montpellier , France

      Nantes , France

      Vantoux , France

      Paris , France

      Stuttgart , Germany

      Tuebingen , Germany

      Erlangen , Germany

      Muenchen , Germany

      Wuerzburg , Germany

      Bonn , Germany

      Magdeburg , Germany

      Gera , Germany

      Berlin , Germany

      Hamburg , Germany

      Szeged , Hungary

      Budapest , Hungary

      Debrecen , Hungary

      Roma , Italy

      Milano , Italy

      Orbassano , Italy

      Arezzo , Italy

      Catania , Italy

      Milano , Italy

      Napoli , Italy

      Terni , Italy

      Wroclaw , Poland

      Bydgoszcz , Poland

      Tarnow , Poland

      Warszawa , Poland

      Slupsk , Poland

      Poznau0144 , Poland

      Badalona , Spain

      Barcelona , Spain

      Caceres , Spain

      Girona , Spain

      Valencia , Spain

      Barcelona , Spain

      Madrid , Spain

      Madrid , Spain

      Madrid , Spain

      Sevilla , Spain

      Stockholm , Sweden

      Uppsala , Sweden

      Middlesbrough , United Kingdom

      London , United Kingdom

      London , United Kingdom

      London , United Kingdom

      Edinburgh , United Kingdom

      Wirral , United Kingdom

      You can join this study in:

      Study Steps

      How Complex Will My Study Be and What Phases Will I Go Through?

      In this clinical trial, the steps a patient needs to take differ depending on the treatment arm they are assigned to:

      Arm A: Pembrolizumab + Surgery

      1. Receive 3 preoperative cycles of pembrolizumab.
      2. Undergo standard of care surgery including radical cystectomy (RC) plus Pelvic Lymph Node Dissection (PLND).
      3. Receive 14 cycles of postoperative pembrolizumab.

      Arm B: Surgery alone

      1. Receive standard of care surgery alone, which includes radical cystectomy (RC) plus Pelvic Lymph Node Dissection (PLND).

      Arm C: Enfortumab Vedotin + Pembrolizumab + Surgery

      1. Receive 3 preoperative cycles of enfortumab vedotin + pembrolizumab.
      2. Undergo standard of care surgery including radical cystectomy (RC) plus Pelvic Lymph Node Dissection (PLND).
      3. Receive 6 cycles of postoperative enfortumab vedotin + pembrolizumab.
      4. Receive 8 cycles of pembrolizumab alone.

      Each cycle mentioned above lasts 21 days.


      Diseases Under Investigation

      What Conditions Qualify Me for This Study?

      To join the study, you need to have the following diseases:

      1. A histologically confirmed diagnosis of urothelial carcinoma/muscle-invasive bladder cancer (MIBC) with classifications cT2-T4aN0M0 or T1-T4aN1M0 and a predominant (≥50%) urothelial histology, which is to be confirmed by Blinded Independent Central Review (BICR).
      2. Clinically nonmetastatic bladder cancer as determined by imaging.

      These are the diseases specifically mentioned that you need to have for inclusion in the study.


      Terms and conditions

      What Requirements I Have to Meet To Join This Study?

      When Am I Eligible to Join the Study?

      Inclusion Criteria for the study:

      1. Diagnosis of Urothelial Carcinoma/Muscle-invasive bladder cancer (MIBC): Participants must have a histologically confirmed diagnosis of urothelial carcinoma/MIBC (stage cT2-T4aN0M0 or T1-T4aN1M0) with at least 50% urothelial histology. This needs to be confirmed by Blinded Independent Central Review (BICR), which involves review of pathology and/or imaging without the reviewers knowing the clinical data.
      2. Nonmetastatic Cancer: Participants’ bladder cancer must be clinically nonmetastatic, as determined by imaging studies.
      3. Suitability for Surgery: Participants must be eligible for radical cystectomy (RC) with pelvic lymph node dissection (PLND), and agree to undergo the surgery with the intent to cure. This surgery involves removing the bladder and dissecting the pelvic lymph nodes to check for cancer spread.
      4. Cisplatin Ineligibility: Participants either must not be suitable for treatment with cisplatin chemotherapy due to reasons such as impaired renal function (creatinine clearance between 30 to 59 mL/min), Eastern Cooperative Oncology Group (ECOG) Performance Status of 2, audiometric hearing loss of grade 2 or higher according to Common Terminology Criteria for Adverse Events (CTCAE) v.4, or New York Heart Association (NYHA) Class III heart failure, or they must be eligible but decline treatment with cisplatin.
      5. Transurethral Resection: Participants must have undergone a transurethral resection (TUR) of the bladder tumor, with tissue provided for central pathology assessment, including determination of urothelial histology and PD-L1 expression.
      6. ECOG Performance Status: Participants must have an ECOG performance status of 0, 1, or 2, which is a measure to assess how the disease affects daily living abilities.
        • 0 indicates fully active, able to carry on all pre-disease activities without restriction.
        • 1 indicates restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature.
        • 2 indicates ambulatory and capable of all self-care but unable to carry out any work activities; up and about more than 50% of waking hours.
      7. Adequate Organ Function: Participants must have sufficient organ function, but the specific criteria for this were not outlined in the section provided.
      8. Contraception for Men: Male participants must agree to use contraception and refrain from donating sperm during the intervention period and for at least 180 days after the last dose of enfortumab vedotin. If only receiving pembrolizumab or undergoing surgery, no contraception is required.
      9. Contraception for Women: Female participants must not be pregnant, not breastfeeding, and either not be of childbearing potential or agree to use highly effective contraceptive methods or be abstinent during the intervention period and for an appropriate duration after the last dose of the study drugs.
      10. Pregnancy Test: Women of childbearing potential must have a negative highly sensitive pregnancy test within 24 hours before the first dose of study intervention.

      Please let me know if you require further information regarding any of the medical terms listed above.

      What Reasons Could Exclude Me from the Study?

      Here are the conditions and explanations of medical terms under which you *cannot* take part in the study:

      Exclusion Criteria:

      1. Progressing Nonurothelial Malignancy or Recent Treatment: A nonurothelial cancer that is getting worse or has needed active cancer treatment within the past 3 years.
      2. Advanced Cancer Stage: Has cancer spread with N2 stage (cancer in lymph nodes beyond immediate region of the tumor) or has metastatic disease (M1), meaning the cancer has spread to distant parts of the body.
      3. Prior Treatments for Bladder Cancer: Received any previous systemic treatment, combination of chemotherapy and radiation therapy (chemoradiation), or radiation therapy specifically for muscle-invasive or non-muscle invasive bladder cancer.
      4. Prior Therapy With Specific Immunotherapies: Received treatment with anti-PD-1, anti-PD-L1, anti-PD-L2 or any agent targeting T-cell receptors, which are parts of the immune system.
      5. Recent Cancer Therapy: Received systemic anticancer therapy including experimental drugs within the last 3 years.
      6. Prior Radiotherapy to the Bladder: If you have received any radiotherapy treatment on your bladder in the past.
      7. Prior Partial Cystectomy: Received a surgery to remove part of the bladder due to cancer.
      8. Recent Live Vaccines: Received a live or live-attenuated (weakened) vaccine within 30 days prior to the first dose of the study medication.
      9. Participation in Other Studies: Currently participating, or participated within the last 4 weeks, in another clinical study involving experimental drugs or medical devices.
      10. Ongoing Neuropathy: Experiencing ongoing nerve-related sensory or motor difficulties rated Grade 2 or higher.
      11. Immunodeficiency or Recent Immunosuppressive Therapy: Having an immunodeficiency diagnosis or received chronic systemic steroids or any immunosuppressive therapy within one week before the first dose of study drug.
      12. Allergy to Study Drugs or Their Ingredients: Hypersensitivity to monoclonal antibodies (like pembrolizumab) or severe hypersensitivity (Grade 3 or higher) to enfortumab vedotin or any of its components.
      13. Eye Conditions: Active eye inflammation or ulcerations, although clinics may admit participants with superficial keratitis if it’s being treated adequately.
      14. Recent Autoimmune Disease Therapy: Active autoimmune disease needing systemic therapy in the past 2 years. However, replacement therapies like thyroid hormone, insulin, or corticosteroids for adrenal or pituitary insufficiency are allowed.
      15. Uncontrolled Diabetes: Uncontrolled diabetes which is not adequately managed with medication or diet.
      16. Prior Pneumonitis or Current Lung Inflammation: A history of non-infectious lung inflammation that required steroids, or has current pneumonitis, an inflammation of lung tissue.
      17. Active Infections: Any active infection that is severe enough to need systemic treatment.
      18. Prior Organ Transplant: Having received a transplant of tissue or an organ from another person (allogeneic transplant).

      These criteria help ensure the safety of participants and the integrity of the study results.


      Investigational Medicinal Product

      What Products Are Being Used in This Study?

      The drugs involved in the study and their active substances are as follows:

      1. Pembrolizumab (Active substance: Pembrolizumab)
        • Pembrolizumab, also known by its trade name KEYTRUDA®, is an anti-PD-1 (programmed death receptor-1) therapy that works by increasing the immune system’s ability to detect and fight tumor cells.
      2. Enfortumab Vedotin (Active substance: Enfortumab Vedotin)
        • Enfortumab Vedotin, also known by its trade name Padcev™, is an antibody-drug conjugate that targets Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer. It delivers a cell-killing agent directly to the tumor cells.

      Have the Medicinal Substances Used in the Trial Been Previously Studied in Medicine?

      The clinical trial involves the following active substances:

      1. Pembrolizumab: Pembrolizumab is known to medicine and the medical literature. It is an immunotherapy drug used to treat various forms of cancer through its action as a PD-1 (programmed death-1) inhibitor.
      2. Enfortumab Vedotin: Enfortumab Vedotin is also known to medicine and the medical literature. It is an antibody-drug conjugate used to treat urothelial cancer, particularly when other treatments such as chemotherapy or immunotherapy have not worked or are not suitable.

      Study ID

      CT-EU-00022028

      Recruitment status

      Recruting new patients

      Start of the trial

      5 years ago

      Study phase

      Phase
      III