Clinical trial NCT01310803: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Carcinoma in Situ
Transitional Cell Carcinoma
Non-muscle Invasive Bladder Cancer
Keywords: Urinary Bladder Neoplasms
Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases
TURBT
Valstar
Lead sponsor: Endo Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2011-03-09
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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

Primary outcomes:
measure: 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.
timeFrame: 2 years
Secondary outcomes:
measure: 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
timeFrame: 2 years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: BCG Oncology
state: Arizona
city: Denver
country: United States
facility: The Urology Center of Colorado
state: Colorado
city: Cumberland
country: United States
facility: Urology Associates
state: Maryland
city: Sewell
country: United States
facility: Delaware Valley Urology
state: New Jersey
city: Syracuse
country: United States
facility: Associated Medical Professionals of New York
state: New York
city: Bala-Cynwyd
country: United States
facility: Urologic Consultants of SE PA
state: Pennsylvania
Study officials:
affiliation: H. Lee Moffitt Cancer Center and Research Institute
name: Philippe E Spiess, MD, MS, FACS, FRCS(C)
role: PRINCIPAL_INVESTIGATOR
References: