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

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

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).

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • BCG Oncology
  • Colorado
    • Denver, Colorado, United States, 80211
      • The Urology Center of Colorado
  • Maryland
    • Cumberland, Maryland, United States, 21502
      • Urology Associates
  • New Jersey
    • Sewell, New Jersey, United States, 08080
      • Delaware Valley Urology
  • New York
    • Syracuse, New York, United States, 13210
      • Associated Medical Professionals of New York
  • Pennsylvania
    • Bala-Cynwyd, Pennsylvania, United States, 19004
      • Urologic Consultants of SE PA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Endo Pharmaceuticals
• Investigators: Principal Investigator: Philippe E Spiess, MD, MS, FACS, FRCS(C), H. Lee Moffitt Cancer Center and Research Institute

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): January 1, 2012

Study Registration Dates

• First Submitted: March 4, 2011
• First Submitted That Met QC Criteria: March 8, 2011
• First Posted (Estimate): March 9, 2011

Study Record Updates

• Last Update Posted (Actual): October 5, 2017
• Last Update Submitted That Met QC Criteria: September 7, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Neoplasms; Urinary Bladder Neoplasms; Urologic Diseases; Urogenital Neoplasms; Neoplasms by Site; Urologic Neoplasms; TURBT; Urinary Bladder Diseases; Valstar
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma in Situ; Carcinoma; Carcinoma, Transitional Cell; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Valrubicin
• Other Study ID Numbers: EN3329-301