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

Phase 3

Terminated

• Conditions: Non-muscle Invasive Bladder Cancer; Carcinoma in Situ; Transitional Cell Carcinoma
• Interventions: Drug: VALSTAR - Maintenance Therapy; Other: No Maintenance treatment ( Standard of Care)

• Registration Number: NCT01310803
• Lead Sponsor: Endo Pharmaceuticals

Brief 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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-03-04
• Study First Submitted QC: 2011-03-08
• Study First Posted: 2011-03-09
• Study Start: 2011-05
• Primary Completion: 2012-01
• Study Completion: 2012-01
• Results First Submitted: 2014-10-16
• Results First Submitted QC: 2014-10-16
• Results First Posted: 2014-10-22
• Status Verified: 2017-09
• Last Update Submitted: 2017-09-07
• Last Update Posted: 2017-10-05

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 1

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Maintenance therapy	VALSTAR - Maintenance Therapy	Chemotherapeutic: EN3329-301 (VALSTAR)
No Maintenance (Standard of care)	No Maintenance treatment ( Standard of Care)	Subjects randomized to No Maintenance (Standard of Care) will not receive any additional intravesical therapy

Primary Outcome Measures

Name	Time	Method
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.	2 years	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).

Secondary Outcome Measures

Name	Time	Method
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	2 years	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

Trial Locations

Locations (6)

Urology Associates; 🇺🇸 Cumberland, Maryland, United States

Associated Medical Professionals of New York; 🇺🇸 Syracuse, New York, United States

BCG Oncology; 🇺🇸 Phoenix, Arizona, United States

Delaware Valley Urology; 🇺🇸 Sewell, New Jersey, United States

Urologic Consultants of SE PA; 🇺🇸 Bala-Cynwyd, Pennsylvania, United States

The Urology Center of Colorado; 🇺🇸 Denver, Colorado, United States