Intervention: Valrubicin
Trial phase: Phase 3
ATC code: L01DB09
SMILES: [H][C@]1(O[C@H]2C[C@H](NC(=O)C(F)(F)F)[C@H](O)[C@H](C)O2)C[C@](O)(C(=O)COC(=O)CCCC)Cc2c(O)c3c(c(O)c21)C(=O)c1c(OC)cccc1C3=O
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 1
Group description: Chemotherapeutic: EN3329-301 (VALSTAR)

VALSTAR - Maintenance Therapy: Treatment phase - 10 monthly intravesical installations starting 10 to 12 weeks after the beginning of induction. Follow-up phase
Eligibility criteria:
Inclusion Criteria:

Is 18 years of age and older at time of consent signing
Have histologically confirmed diagnosis of CIS of the bladder and received valrubicin induction therapy per the labeled indication.

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
Is available for the duration of the study including follow-up (minimum 12 months from randomization)
Have an Eastern Cooperative Oncology Group (ECOG) performance status grade of 2 or less
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
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
Is able to understand and give written informed consent

Exclusion Criteria:

Have current or previous history of muscle-invasive bladder cancer (MIBC)
Current or previous history of lymph node positive and/or metastatic bladder cancer
Have current evidence of pure squamous cell carcinoma, pure adenocarcinoma or pure undifferentiated carcinoma of the bladder
Is currently receiving systemic anti-cancer therapy (cytotoxic/cytostatic, immunotherapy or radiation)
Received treatment with an investigational agent within 30 days or 5 half-lives prior to randomization, whichever is longer
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
Received treatment with valrubicin other than induction within 3 months prior to randomization

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
Absolute neutrophil count (ANC) <1000/µL and hemoglobin <10 g/dL
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
Female subjects who are pregnant or lactating
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
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)
Is unable to tolerate intravesical administration or intravesical surgical manipulation (cystoscopy or biopsy) even with premedication
Have ongoing clinically significant active infections
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