DN24-02 as Adjuvant Therapy in Subjects With High Risk HER2+ Urothelial Carcinoma
Condition: Urothelial Carcinoma
MeSH terms: Carcinoma; Carcinoma, Transitional Cell
Intervention: DN24-02; Standard of Care
Intervention description: DN24-02 is an autologous cellular immunotherapy product designed to stimulate an immune response against HER2/neu. It consists of autologous peripheral blood mononuclear cells (PBMCs), including antigen presenting cells (APCs), which are activated ex vivo with a recombinant fusion protein, BA7072.; Observation only until documentation of disease recurrence.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 142.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Bladder cancer; Renal pelvis cancer; Ureteral cancer; Urethral cancer; Bladder; Renal pelvis; Ureter; Urethra; Immune therapy; Immunotherapy; Vaccine; Dendritic cells; Antigen-presenting cells; Antigen presenting cells; Cancer vaccine; Urothelial carcinoma; Urothelial neoplasms; Neoplasms by site; Neoplasms

Summary:

      This study was conducted to examine survival, disease-free survival, safety, and the
      magnitude of the immune response induced following administration of DN24-02 in subjects with
      HER2+ urothelial carcinoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histopathologic evidence of urothelial carcinoma, based on local pathology report.

          -  High risk urothelial carcinoma, in subjects with or without prior neoadjuvant
             chemotherapy, defined as positive lymph node status (N+), or pathological stage ≥
             pathological tumor (pT2) in patients who either have negative lymph node status (N0)
             or have no evaluable lymph nodes (Nx).

          -  Radical surgical resection was performed ≤ 84 days (12 weeks) prior to registration.

          -  No evidence of residual disease or metastasis following surgical resection which
             includes: absence of invasive cancer at the margins in the surgical specimens and
             confirmation by CT scan of chest, abdomen and pelvis obtained at least 28 days
             following surgical resection and ≤ 28 days prior to registration.

          -  HER2/neu tissue expression ≥ 1+ by immunohistochemistry (IHC). Available biopsy
             specimens from the primary tumor and involved lymph nodes are be submitted to the
             central pathology laboratory prior to registration for confirmation of HER2/neu tissue
             expression.

          -  Last neoadjuvant chemotherapy treatment administered at least 60 days prior to
             registration.

          -  Left ventricular ejection fraction ≥ 50% on multigated acquisition (MUGA) scan or
             echocardiogram obtained at least 28 days following surgery and ≤ 28 days prior to
             registration.

          -  Women of child-bearing potential have a negative serum pregnancy test result ≤ 28 days
             prior to registration and agree not to breastfeed during investigational treatment
             with DN24-02 and for 28 days following the final infusion of DN24-02.

          -  All males and premenopausal females who have not been surgically sterilized have
             agreed to practice a method of birth control considered by the Investigator to be
             effective and medically acceptable for at least 14 days prior to registration,
             throughout treatment, and for 28 days following the final infusion of DN24-02.

          -  Adequate hematologic, renal, and liver function.

          -  Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.

        Exclusion Criteria:

          -  A history of stage III or greater non-urothelial cancer. Exceptions include: Subject
             with basal or squamous cell skin cancers that has been adequately treated who are
             disease-free at the time of registration. Subjects who have been disease-free and off
             treatment for ≥ 10 years at the time of registration.

          -  A history of stage I or II non-urothelial cancer. Exceptions include: Subjects who
             have been disease-free and off treatment for ≥ 3 years at the time of registration.
             Subjects with incidental prostate cancer diagnosed at the time of cystoprostatectomy.
             Subjects with basal or squamous cell skin cancer.

          -  Partial cystectomy in the setting of bladder cancer primary tumor.

          -  Partial nephrectomy in the setting of renal pelvis primary tumor.

          -  Adjuvant systemic therapy for urothelial or prostatic carcinoma following surgical
             resection.

          -  Adjuvant radiation therapy for urothelial or prostatic carcinoma following surgical
             resection.

          -  Incidental prostate cancer with detectable post-operative (radical cystoprostatectomy)
             prostate specific antigen (PSA) levels ≤ 28 days prior to registration.

          -  Any major surgery (e.g., surgery requiring general anesthesia) ≤ 28 days prior to
             registration.

          -  Systemic treatment on any investigational clinical trial ≤ 28 days prior to
             registration.

          -  Systemic glucocorticoid or immunosuppressive therapy use ≤ 28 days prior to
             registration.

          -  Any infection requiring parenteral antibiotic therapy or causing fever (i.e.,
             temperature > 100.5°F or > 38.1°C) ≤ 7 days prior to registration.

          -  A history of allergic reactions attributed to compounds of similar chemical or
             biologic composition to DN24-02 or Granulocyte-macrophage colony-stimulating factor
             (GM-CSF).

          -  Any medical intervention, has any other condition, or has any other circumstance
             which, in the opinion of the Investigator or the Dendreon Medical Monitor, could
             compromise adherence with study requirements or otherwise compromise the study's
             objectives.