Bladder Cancer study: Enfortumab Vedotin vs Pembrolizumab
Official title Enfortumab Vedotin and Pembrolizumab Combined With Radiotherapy in Muscle Invasive Bladder Cancer
ClinicalTrials.gov ID: NCT06470282
What this study is testing
What is Enfortumab Vedotin (Padcev)?
An investigational intravenous medicine being studied for treating muscle‑invasive bladder cancer. It is designed to target a protein on tumor cells and deliver a toxic drug to kill them.
Also referred to as Padcev.
Plain-language explanation of the investigational treatment. It is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- This study is testing whether enfortumab vedotin plus pembrolizumab and radiation can safely treat muscle‑invasive bladder cancer. It also looks at the best dose and how well it works.
- Who it's for
- You may be able to join if you have muscle‑invasive bladder cancer that is stage II or IIIA and you are not a good candidate for standard chemotherapy and surgery.
- What's involved
- You would receive the drug enfortumab vedotin and the drug pembrolizumab, plus daily radiation treatments. You will have regular visits for blood tests, scans, and doctor check‑ins to monitor side effects and tumor response.
- Time commitment
- The study lasts about 6 to 12 months, with daily radiation for a few weeks and follow‑up visits every few months.
- Phase 2: a mid-size study of how well it works
- Time commitment: about 5 years
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join if
- Biopsy-confirmed muscle-invasive bladder cancer (cT2,T3,T4a). (Note: Tissue samples are required.) (Participants with cT3/T4a staged disease will be...
- Urothelial histology present. Mixed histologies other than small cell/neuroendocrine are allowed as long as some urothelial histology is present.
- Must be judged by the investigator to be ineligible for radical cystectomy or electing not to undergo radical cystectomy.
- Must be eligible for and agree to receive bladder irradiation as determined by the treating investigator.
- Must have a TURBT within 8 weeks of combination treatment start with viable tumor content.
You likely can't join if
- Presence of distant metastases on imaging (M1 disease).
- Presence of ≥ N2 disease on imaging (N1 disease allowed, but participants with N1 disease will be capped at 25% of patients treated at RP2D).
- Presence of small cell / neuroendocrine histology in tumor sample (any content).
- Absence of urothelial histology in TURBT tumor sample (pure variant histology).
- Presence of untreated upper tract urothelial cancer.
- Presence of severe hydronephrosis precluding therapy in the judgement of the treating physician.
See the full eligibility criteria
Who can join
- Biopsy-confirmed muscle-invasive bladder cancer (cT2,T3,T4a). (Note: Tissue samples are required.) (Participants with cT3/T4a staged disease will be capped at 25% of patients treated at RP2D).
- Urothelial histology present. Mixed histologies other than small cell/neuroendocrine are allowed as long as some urothelial histology is present.
- Must be judged by the investigator to be ineligible for radical cystectomy or electing not to undergo radical cystectomy.
- Must be eligible for and agree to receive bladder irradiation as determined by the treating investigator.
- Must have a TURBT within 8 weeks of combination treatment start with viable tumor content. If no viable tumor content is present on TURBT, archival TURBT sample confirming MIBC diagnosis can be used instead.
- Patients who have autoimmune disease will be evaluated on a case-by-case basis and can only enroll so long as participants are not on active immunosuppression with a corticoid steroid allowance exceeding 10mg of...
- Age \>= 18 years.
- Absolute neutrophil count ≥ 1,500/microliter (mcL).
- Platelets \>= 100,000/mcL.
- Total bilirubin \<= 1.5 × upper limit of normal, unless elevated due to Gilbert's syndrome and direct bilirubin is within normal limits.
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase (SGOT)) \<= 2.5 X institutional upper limit of normal.
- International normalized ratio (INR) OR prothrombin time (PT) \<= 1.5 × upper limit of normal (ULN).
- Activated partial thromboplastin time (aPTT) \<= 1.5 × ULN. \ If participant is receiving anticoagulant therapy, as long as PT or aPTT is within therapeutic range of intended use of anticoagulants, participant is...
- Ability to understand and the willingness to sign a written informed consent document.
- Human immunodeficiency virus (HIV)-infected individuals on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
- 12\. Participants who are Hepatitis B surface antigen (HBsAg) positive are eligible if they have an undetectable hepatitis B Virus (HBV) viral load prior to randomization.
- Participants with a history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening.
- Women of child-bearing potential and men with sexual partners of childbearing potential must agree to use adequate contraception for the duration of study participation. Enfortumab vedotin (EV) may cause fetal harm.
- Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 8 weeks after last administration of study treatment.
What rules you out
- Presence of distant metastases on imaging (M1 disease).
- Presence of ≥ N2 disease on imaging (N1 disease allowed, but participants with N1 disease will be capped at 25% of patients treated at RP2D).
- Presence of small cell / neuroendocrine histology in tumor sample (any content).
- Absence of urothelial histology in TURBT tumor sample (pure variant histology).
- Presence of untreated upper tract urothelial cancer.
- Presence of severe hydronephrosis precluding therapy in the judgement of the treating physician.
- Presence of extensive carcinoma in situ (CIS) is exclusionary; moderate CIS that could still benefit from radiation treatment in the judgement of treating physician is allowed.
- Baseline neuropathy grade 2 (G2) or greater.
- Baseline uncontrolled diabetes mellitus. Uncontrolled diabetes is defined as hemoglobin A1c (HbA1c) ≥ 8% or HbA1c 7 to \< 8% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained.
- Prior treatment with systemic immunotherapy or chemotherapy for urothelial cancer. (with the exception of prior systematic therapy treatment \>12 months prior).
- Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to cycle 1 day 1.
- Has received prior radiotherapy within 2 weeks of cycle 1 day 1 or had radiation-related toxicities requiring corticosteroids.
- Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. \ Note: Administration of killed vaccines is allowed.
- Major surgery within 2 weeks prior to first dose of EV. \ Note: Cataract surgery, standard tissue biopsies, and standard of care cardiac devices, such as a pacemaker or stent placed on an elective basis, are allowable...
- 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...
- HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
- Has known active CNS metastases and/or carcinomatous meningitis.
- History of another significant life-limiting malignancy requiring systematic treatment within 2 years prior to the first dose of study drugs, or any evidence of residual disease from a previously diagnosed malignancy.
- Hypersensitivity to pembrolizumab or enfortumab vedotin, or any of their excipients.
- Prior allogeneic stem cell or solid organ transplant.
- Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or current pneumonitis/interstitial lung disease requiring active management.
- Has an active infection requiring systemic therapy that in the judgement of the treating team would preclude treatment with EV, pembrolizumab or RT.
- 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...
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Pregnant and breast feeding participants are excluded from this study because targeted chemotherapy and radiation have the potential for teratogenic or abortifacient effects.
The study team makes the final eligibility decision.
Where it is enrolling
- San Francisco, California, United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part, but confirm specifics with the study team.
How long does this study last?
The study runs about 5 years per participant, based on its public description. The team confirms the exact schedule and number of visits before you enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
This study is enrolling now at San Francisco, California, United States. Enter your location above to see the nearest enrolling site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool that is independent of the study sponsor. Details come from ClinicalTrials.gov. The study team decides eligibility, and your own doctor gives medical advice.