RECRUITING

Enfortumab Vedotin and Pembrolizumab Combined With Radiotherapy in Muscle Invasive Bladder Cancer

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Conditions

Bladder CancerMuscle-Invasive Bladder CarcinomaStage II Bladder Cancer AJCC v8Stage IIIA Bladder Cancer AJCC v8

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This phase Ib/II trial studies the side effects, best dose, and effectiveness of enfortumab vedotin (EV) in combination with pembrolizumab and radiation therapy for treating patients with muscle invasive bladder cancer. Standard of care treatment for muscle invasive bladder cancer is chemotherapy, to shrink the tumor before the main treatment is given (neoadjuvant), followed by surgery to remove all of the bladder as well as nearby tissues and organs (radical cystectomy). In cases where patients are not candidates for the standard of care approach or prefer a bladder sparing option, tri-modality therapy with transurethral resection of bladder tumor (TURBT) followed by combined chemotherapy and radiation therapy is used. Enfortumab vedotin is a monoclonal antibody, enfortumab, linked to an anticancer drug called vedotin. It works by helping the immune system to slow or stop the growth of tumor cells. Enfortumab attaches to a protein called nectin-4 on tumor cells in a targeted way and delivers vedotin to kill them. It is a type of antibody-drug conjugate. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Intensity-modulated radiation therapy is a type of 3-dimensional radiation therapy that uses computer-generated images to show the size and shape of the tumor. Thin beams of radiation of different intensities are aimed at the tumor from many angles. This type of radiation therapy reduces the damage to healthy tissue near the tumor. Giving enfortumab vedotin with pembrolizumab and radiation therapy may work better in treating patients with muscle invasive bladder cancer.

Official Title

Phase Ib/II Study of Enfortumab Vedotin and Pembrolizumab Combined With Radiotherapy as a Bladder-Sparing Trimodality Therapy in Muscle Invasive Bladder Cancer

Quick Facts

Study Start:2025-03-31
Study Completion:2028-01-31
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT06470282

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * 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).
  2. * Urothelial-predominant histology. Mixed histologies other than small cell/neuroendocrine are allowed as long as some urothelial histology is present. Neuroendocrine histology of any component and pure variant (non-urothelial) histology tumors will be excluded. (Patients with \< 50% urothelial histology will be capped at 25% of patients treated at RP2D).
  3. * Must be judged by the investigator to be ineligible for radical cystectomy or electing not to undergo radical cystectomy.
  4. * Must be eligible for and agree to receive bladder irradiation as determined by the treating investigator.
  5. * Must have a TURBT within 8 weeks of combination treatment start with viable tumor content. If no viable tumor content is present on TURBT, the patient will be replaced in the study.
  6. * 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 prednisone or equivalent per day.
  7. * Age \>= 18 years.
  8. * Eastern Cooperative Oncology Group (ECOG) performance status \<= 1.
  9. * Absolute neutrophil count ≥ 1,500/microliter (mcL).
  10. * Platelets \>= 100,000/mcL.
  11. * Hemoglobin \>= 9.0 g/dL or ≥ 5.6 mmol/L.
  12. * Total bilirubin \<= 1.5 × upper limit of normal, unless elevated due to Gilbert's syndrome and direct bilirubin is within normal limits.
  13. * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase (SGOT)) \<= 2.5 X institutional upper limit of normal.
  14. * Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase (SGPT)) \<= 2.5 X institutional upper limit of normal.
  15. * Creatinine clearance glomerular filtration rate (GFR) \>= 30 mL/min/1.73 m\^2, calculated by Cockcroft-Gault or measured using 24-hour creatinine clearance.
  16. * International normalized ratio (INR) OR prothrombin time (PT) \<= 1.5 × upper limit of normal (ULN).
  17. * Activated partial thromboplastin time (aPTT) \<= 1.5 × ULN.
  18. * Ability to understand and the willingness to sign a written informed consent document.
  19. * Human immunodeficiency virus (HIV)-infected individuals on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
  20. * Participants who are hepatitis B virus surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) anti-viral therapy for at least 4-weeks, and have undetectable HBV viral load prior to randomization. Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention.
  21. * Participants with a history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening.
  22. * 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. Women of child-bearing potential must use contraception during treatment with EV and for 120 days after the last dose. Men with female partners who are women of child-bearing potential must use contraception during treatment with EV and for 120 days after the last dose. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Acceptable methods include barrier method, hormonal method, as well as intrauterine devices
  23. * 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.
  1. * Presence of distant metastases on imaging (M1 disease).
  2. * Presence of lymph nodes concerning for regional disease spread (lymph node (LN) \> 1.0 cm on short axis present on cross sectional imaging) that is attributable to cancer spread (≥ N1 disease).
  3. * Presence of small cell / neuroendocrine histology in tumor sample (any content).
  4. * Absence of urothelial histology in TURBT tumor sample (pure variant histology).
  5. * Presence of untreated upper tract urothelial cancer.
  6. * Presence of moderate/severe hydronephrosis.
  7. * Presence of extensive carcinoma in situ (CIS).
  8. * Baseline neuropathy grade 2 (G2) or greater.
  9. * 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.
  10. * Prior treatment with systemic immunotherapy or chemotherapy for urothelial cancer.\* Note: Prior bacillus calmette-guerin (BCG) and intravesical treatments are allowed
  11. * 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 (e.g., cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), OX40, CD137).
  12. * Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to cycle 1 day 1.
  13. * Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.
  14. * Has received prior radiotherapy within 2 weeks of cycle 1 day 1 or radiation-related toxicities requiring corticosteroids.
  15. * Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention.
  16. * Major surgery within 2 weeks prior to first dose of EV.
  17. * 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.
  18. * HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
  19. * Known additional malignancy that is progressing or has required active treatment within the past 3 years.
  20. * Has known active CNS metastases and/or carcinomatous meningitis.
  21. * History of another significant life-limiting malignancy within 2 years prior to the first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy.
  22. * Hypersensitivity to pembrolizumab or enfortumab vedotin, or any of their excipients.
  23. * Prior allogeneic stem cell or solid organ transplant.
  24. * Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
  25. * Has an active infection requiring systemic therapy.
  26. * 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.
  27. * History of hepatitis B with detectable HBV viral load (participants who are HBsAg positive are eligible if they have received HBV anti-viral therapy for at least 4 weeks, and have undetectable HBV viral load prior to randomization) or known active hepatitis C virus (defined as detectable HCV RNA .\[qualitative\]) infection.
  28. * Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  29. * Has had an allogenic tissue/solid organ transplant.
  30. * Pregnant and chest feeding participants are excluded from this study because targeted chemotherapy and radiation have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with EV+pembrolizumab, breastfeeding should be discontinued if the mother is treated with these investigational products.

Contacts and Locations

Study Contact

UCSF Genitourinary Medical Oncology Recruitment
CONTACT
877-827-3222
GUTrials@ucsf.edu

Principal Investigator

Vadim Koshkin, MD
PRINCIPAL_INVESTIGATOR
University of California, San Francisco

Study Locations (Sites)

University of California, San Francisco
San Francisco, California, 94143
United States

Collaborators and Investigators

Sponsor: University of California, San Francisco

  • Vadim Koshkin, MD, PRINCIPAL_INVESTIGATOR, University of California, San Francisco

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-03-31
Study Completion Date2028-01-31

Study Record Updates

Study Start Date2025-03-31
Study Completion Date2028-01-31

Terms related to this study

Additional Relevant MeSH Terms

  • Bladder Cancer
  • Muscle-Invasive Bladder Carcinoma
  • Stage II Bladder Cancer AJCC v8
  • Stage IIIA Bladder Cancer AJCC v8