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

Study Overview
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Brief Summary
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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).

Official Title
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A PHASE 3B, RANDOMIZED, OPEN-LABEL, 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

Conditions
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Carcinoma in Situ, Transitional Cell Carcinoma, Non-muscle Invasive Bladder Cancer

Intervention / Treatment
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* Drug: VALSTAR - Maintenance Therapy
* Other: No Maintenance treatment ( Standard of Care)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Maintenance therapy<br>Chemotherapeutic: EN3329-301 (VALSTAR) | Drug: VALSTAR - Maintenance Therapy<br>* Treatment phase - 10 monthly intravesical installations starting 10 to 12 weeks after the beginning of induction. Follow-up phase<br>* Other names: VALSTAR;|
| Other: No Maintenance (Standard of care)<br>Subjects randomized to No Maintenance (Standard of Care) will not receive any additional intravesical therapy | Other: No Maintenance treatment ( Standard of Care)<br>* Subjects randomized to No Maintenance (Standard of Care) will not receive any additional intravesical therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Evaluate the Efficacy of Maintenance Therapy With Valrubicin After Induction With Valrubicin, as Compared to Induction With Valrubicin Only in Subjects With CIS of the Bladder. | time interval from randomization to an event. An event is defined as tumor recurrence (any stage or grade), tumor progression to muscle-invasive bladder cancer (MIBC), metastatic bladder cancer or death from any cause, whichever occurs first. Tumor recurrence or progression must be documented by biopsy/transurethral resection of bladder tumor (TURBT). | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Evaluate the Safety and Tolerability of Maintenance Therapy With Valrubicin After Induction With Valrubicin, as Compared to Induction With Valrubicin Only in Subjects With CIS of the Bladder | The occurrence of serious adverse events (SAEs), occurrence of local adverse reactions (LARs), results of vital signs, physical exams and laboratory test, and study discontinuation due to inability to complete valrubicin instillations | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Urinary Bladder Neoplasms, Neoplasms, Urologic Neoplasms, Urogenital Neoplasms, Neoplasms by Site, Urinary Bladder Diseases, Urologic Diseases, TURBT, Valstar