Multi-center Study to Evaluate the Efficacy and Safety of Maintenance Therapy With Valrubicin Versus no Maintenance, in Subjects Treated With Valrubicin Induction for Carcinoma in Situ (CIS) of the Bladder
Condition: Carcinoma in Situ; Transitional Cell Carcinoma; Non-muscle Invasive Bladder Cancer
MeSH terms: Carcinoma; Carcinoma in Situ; Non-Muscle Invasive Bladder Neoplasms; Carcinoma, Transitional Cell
Intervention: VALSTAR - Maintenance Therapy; No Maintenance treatment ( Standard of Care)
Intervention description: Treatment phase - 10 monthly intravesical installations starting 10 to 12 weeks after the beginning of induction. Follow-up phase; Subjects randomized to No Maintenance (Standard of Care) will not receive any additional intravesical therapy
Intervention MeSH terms: Valrubicin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Urinary Bladder Neoplasms; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urinary Bladder Diseases; Urologic Diseases; TURBT; Valstar

Summary:

      This is a Phase 3b open-label, randomized, parallel-arm, multicenter study to evaluate the
      efficacy and safety of 10 monthly intravesical administrations of maintenance therapy with
      valrubicin following induction with valrubicin as compared to induction with valrubicin only
      in subjects with CIS of the bladder. The randomization will be 1:1 and subjects will be
      stratified by tumor type (CIS plus papillary disease vs. CIS only) and time from last
      bacillus Calmette-Guerin (BCG) failure (>1 year vs. <1 year).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Is 18 years of age and older at time of consent signing

          2. Have histologically confirmed diagnosis of CIS of the bladder and received valrubicin
             induction therapy per the labeled indication.

          3. Is disease-free following induction with intravesical valrubicin

               -  Disease-free is defined as negative biopsy 10 to 12 weeks after the initiation of
                  valrubicin induction

               -  Valrubicin induction is defined as having received at least 3 of 6 weekly
                  instillations

          4. Is available for the duration of the study including follow-up (minimum 12 months from
             randomization)

          5. Have an Eastern Cooperative Oncology Group (ECOG) performance status grade of 2 or
             less

          6. Have no evidence of urothelial carcinoma involving the upper urinary tract or
             prostatic urethra (confirmed by extravesical work up, which may include radiological
             imaging and/or biopsy) within 6 months prior to randomization

          7. Subjects (male and female) of child-bearing potential (including female subjects who
             are post-menopausal for less than 1 year) must be willing to practice abstinence or
             effective contraception (as defined by the investigator) during the study and be
             willing and able to continue contraception for 30 days after their last dose of study
             treatment

          8. Is able to understand and give written informed consent

        Exclusion Criteria:

          1. Have current or previous history of muscle-invasive bladder cancer (MIBC)

          2. Current or previous history of lymph node positive and/or metastatic bladder cancer

          3. Have current evidence of pure squamous cell carcinoma, pure adenocarcinoma or pure
             undifferentiated carcinoma of the bladder

          4. Is currently receiving systemic anti-cancer therapy (cytotoxic/cytostatic,
             immunotherapy or radiation)

          5. Received treatment with an investigational agent within 30 days or 5 half-lives prior
             to randomization, whichever is longer

          6. Received treatment with an intravesical chemotherapeutic agent (other than valrubicin
             or a single administration of mitomycin C post-transurethral resection of bladder
             tumor [TURBT]) within 3 months prior to randomization

          7. Received treatment with valrubicin other than induction within 3 months prior to
             randomization

          8. Have contraindication to valrubicin

               -  Known hypersensitivity to anthracyclines or polyoxyl castor oil

               -  Small bladder capacity, i.e. unable to tolerate a 75 mL instillation

               -  Concurrent urinary tract infection

          9. Absolute neutrophil count (ANC) <1000/µL and hemoglobin <10 g/dL

         10. Have active cardiovascular disease such as myocardial infarction within the past 3
             months, unstable angina pectoris, congestive heart failure (NYHA Class III or IV) or
             uncontrolled cardiac arrhythmia

         11. Female subjects who are pregnant or lactating

         12. Subjects of childbearing potential who are unwilling to practice abstinence or
             effective contraception (as defined by investigator) during the study and for 30 days
             after last dose of study treatment

         13. Have current or history of documented or suspected malignancy of any organ system
             (diagnosed, treated or untreated) within the past 5 years (with the exception of
             adequately treated basal cell or squamous cell carcinoma of the skin and asymptomatic
             non-metastatic prostate cancer either previously successfully treated or currently
             under active surveillance or receiving hormone therapy only)

         14. Is unable to tolerate intravesical administration or intravesical surgical
             manipulation (cystoscopy or biopsy) even with premedication

         15. Have ongoing clinically significant active infections

         16. Have any medical or psychiatric condition which, in the opinion of the investigator,
             would preclude the participant from adhering to the protocol or completing the trial
             per protocol