Clinical trial NCT00461591: Single Dose Intravesical Apaziquone Postoperative in Patients Undergoing TURBT for Noninvasive Bladder Cancer (SPI-611)
Official title: A Multicenter, Randomized, Placebo-Controlled, Double-Blind, Phase 3 Trial of Single Dose Intravesical Apaziquone (EOquin®) as a Surgical Adjuvant Instilled in the Early Postoperative Period in Patients Undergoing Transurethral Resection for Noninvasive Bladder Cancer (Protocol SPI-611)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Bladder Cancer
Keywords: Noninvasive Bladder Cancer
Lead sponsor: Spectrum Pharmaceuticals, Inc
Sponsor class: INDUSTRY
First posted: 2007-04-18
Enrollment: 802
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: The purpose of this study was to evaluate the 2-Year Recurrence Rate of bladder cancer in randomized patients with tumor histology Ta, G1-G2 who received TransUrethral Resection of Bladder Tumor (TURBT) plus apaziquone versus those who received TURBT plus placebo.

Detailed description: This was a Phase 3, multicenter, randomized, double-blind, placebo-controlled study. Within 14 days of Screening, eligible patients underwent a TURBT during Visit 1 (Day 0) following which they were immediately randomized in a 1:1 ratio to receive either placebo or 4 mg apaziquone, instilled in a volume of 40 mL into the bladder within 6 hours from the end of the TURBT procedure. After a 60-minute retention period, study drug was drained from the bladder.

A postoperative follow-up examination and review of the local pathology report were performed at Visit 2, which occurred 21 days (±10 days) after the TURBT (Week 3).

* If the histology of the patient's tumor was confirmed as Ta, G1-G2 (ie, low grade according to World Health Organization \[WHO\]/International Society of Urologic Pathology \[ISUP\] classification), no further treatment was given and the patient was observed cystoscopically every 3 months through Year 2 for tumor recurrence (Visit 3 through Visit 10).
* If the histology of the patient's tumor was other than Ta, G1 or G2 (low grade \[WHO/ISUP classification\]), further treatment was given in accordance with current treatment guidelines, and the patient was followed up cystoscopically every 3 months through Year 2 for tumor recurrence (Visit 3 through Visit 10).

All patients were to be followed for 2 years.

Eligibility criteria: Inclusion Criteria: (All questions must be answered YES)

* Has the patient given written informed consent?
* Is the patient at least 18 years old?
* Does the patient have transitional cell carcinoma of the bladder with clinically apparent stage Ta, grade G1-G2?
* If the patient is a female of childbearing potential, is she using an acceptable/effective method of contraception?
* If the patient is a female of childbearing potential, has she had a negative serum pregnancy test within the past 14 days?
* Is the patient willing and able to abide by the protocol?

Exclusion Criteria: (All questions must be answered NO)

* Does the patient have more than 4 bladder tumors?
* Does any single bladder tumor exceed 3.5 cm in diameter?
* Does the patient have a single, primary (no previous diagnosis of TCC) bladder tumor \<0.5 cm?
* Has the patient ever received Apaziquone?
* Does the patient have, or has the patient ever had, any bladder tumor known to be other than stage Ta or grade G1 or G2 (low grade \[WHO/ISUP classification\])?
* Does the patient have, or has the patient ever had any bladder tumor with histology other than transitional cell carcinoma?
* Does the patient have, or has the patient ever had, carcinoma in situ (CIS)?
* Does the patient have an active urinary tract infection?
* Does the patient have a bleeding disorder or a screening platelet count \< 100 x 10\^9/L?
* Does the patient have any unstable medical condition that would make it unsafe for him/her to undergo TURBT under general or spinal anesthesia?
* Does the patient have a screening hemoglobin \< 10 mg/dL, a screening absolute neutrophil count \< 1.5 x 10\^9/L or a screening creatinine \> 2 mg/dL?
* Does the patient have a known immunodeficiency disorder?
* Has the patient received any investigational treatment within the past 30 days?
* Is the patient breast feeding?
* Does the patient have a history of interstitial cystitis?
* Does the patient have a history of allergy to red color food dye?
* Has the patient had transitional cell carcinoma of the bladder within the past 4 months?

Primary outcomes:
measure: Recurrence Rate at 2 Years
timeFrame: 2 years
Secondary outcomes:
measure: Time to Recurrence
timeFrame: 2 years
measure: Progression Rate at 2 Years
timeFrame: 2 years
measure: Time to Progression
timeFrame: 2 years
measure: Number of Recurrences Per Patient
timeFrame: 2 years
measure: Disease Free Interval
timeFrame: 2 years
measure: Disease Free Survival
timeFrame: 2 years
measure: Overall Survival
timeFrame: 2 years
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Alaska Clinical Research Center, LLC
state: Alaska
city: Phoenix
country: United States
facility: BCG Oncology
state: Arizona
city: Sun City
country: United States
facility: Sun Health Research Institute
state: Arizona
city: Burbank
country: United States
facility: Urology Associates Medical Group
state: California
city: Fresno
country: United States
facility: Urology Associates of Central CA
state: California
city: Laguna Woods
country: United States
facility: South Orange County Medical Research Center
state: California
city: Los Angeles
country: United States
facility: Kaiser Permanente Los Angeles Medical Center
state: California
city: Orange
country: United States
facility: Cancer Research Dept/St. Joseph Hospital
state: California
city: San Bernardino
country: United States
facility: San Bernardino Urologic Association
state: California
city: San Francisco
country: United States
facility: VA Medical Center
state: California
city: Denver
country: United States
facility: The Urology Center of Colorado
state: Colorado
city: Middlebury
country: United States
facility: Connecticut Clinical Research Center
state: Connecticut
city: Washington
country: United States
facility: Urologic Surgeons of Washington
state: District of Columbia
city: Lakeland
country: United States
facility: Lakeland Regional Cancer Center
state: Florida
city: Longwood
country: United States
facility: Urology Consultants
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: New Port Richey
country: United States
facility: Advanced Research Institute
state: Florida
city: New Port Richey
country: United States
facility: Advanced Research Institute
state: Florida
city: Ocala
country: United States
facility: Florida Foundation for Healthcare Research
state: Florida
city: Sarasota
country: United States
facility: Florida Urology Specialists
state: Florida
city: Tallahassee
country: United States
facility: Southeastern Research Group, Inc.
state: Florida
city: Gainesville
country: United States
facility: Gainesville Urology, PC
state: Georgia
city: Macon
country: United States
facility: Urological Professional Association
state: Georgia
city: Coeur d'Alene
country: United States
facility: North Idaho Urology
state: Idaho
city: Meridian
country: United States
facility: Idaho Urologic Institute, P.A.
state: Idaho
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Mattoon
country: United States
facility: Urology Associates, SC
state: Illinois
city: Peoria
country: United States
facility: Speciality Care Research
state: Illinois
city: Fort Wayne
country: United States
facility: Northeast Indiana Research, LLC
state: Indiana
city: Jeffersonville
country: United States
facility: Metropolitan Urology
state: Indiana
city: Overland Park
country: United States
facility: Kansas City Urology Care, P.A.
state: Kansas
city: Shreveport
country: United States
facility: Regional Urology, LLC
state: Louisiana
city: Annapolis
country: United States
facility: Anne Arundel Urology
state: Maryland
city: Greenbelt
country: United States
facility: Myron Murdock, MD, LLC
state: Maryland
city: Grand Rapids
country: United States
facility: MMPC Urology
state: Michigan
city: Saint Joseph
country: United States
facility: Lakeside Urology, PC
state: Michigan
city: Troy
country: United States
facility: Michigan Institute of Urology, PC
state: Michigan
city: Missoula
country: United States
facility: Five Valleys Urology
state: Montana
city: Brick
country: United States
facility: Coastal Urological Associates, PA
state: New Jersey
city: Lawrenceville
country: United States
facility: AdvanceMed Research
state: New Jersey
city: Marlton
country: United States
facility: Delaware Valley Urology, LLC-Marlton
state: New Jersey
city: Sewell
country: United States
facility: Deleware Valley Urology, LLC-Washington Township
state: New Jersey
city: Voorhees
country: United States
facility: Delaware Valley Urology, LLC - Voorhees
state: New Jersey
city: Westampton
country: United States
facility: Delaware Valley Urology, LLC-Westampton
state: New Jersey
city: Albuquerque
country: United States
facility: Urology Group of New Mexico
state: New Mexico
city: Albany
country: United States
facility: Capital Region Urological Surgeons
state: New York
city: Albany
country: United States
facility: The Urological Institute of NE NY
state: New York
city: Carmel
country: United States
facility: Adult and Pediatric Urology
state: New York
city: Garden City
country: United States
facility: Accumed Research Associates
state: New York
city: Garden City
country: United States
facility: Urological Surgeons of Long Island, P.C.
state: New York
city: Kingston
country: United States
facility: Hudson Valley Urology, PC
state: New York
city: New York
country: United States
facility: University Urology Associates
state: New York
city: Oneida
country: United States
facility: CNY Urology, PC
state: New York
city: Poughkeepsie
country: United States
facility: Hudson Valley Urology
state: New York
city: Rochester
country: United States
facility: Urology Associates of Rochester, LLC
state: New York
city: Williamsville
country: United States
facility: Center for Urologic Research of WNY, LLC
state: New York
city: Cincinnati
country: United States
facility: TriState Urologic Services PSC, Inc.
state: Ohio
city: Columbus
country: United States
facility: Columbus Urology Research, LLC
state: Ohio
city: Springfield
country: United States
facility: Oregon Urology Institute
state: Oregon
city: Bala-Cynwyd
country: United States
facility: Urologic Consultants of South Eastern Pennsylvania
state: Pennsylvania
city: Lancaster
country: United States
facility: Urological Associates of Lancaster
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Triangle Urology Group
state: Pennsylvania
city: Williamsport
country: United States
facility: Susquehenna Urology
state: Pennsylvania
city: Myrtle Beach
country: United States
facility: Carolina Urologic Research Center
state: South Carolina
city: Germantown
country: United States
facility: The Conrad Pearson Clinic
state: Tennessee
city: Corpus Christi
country: United States
facility: Corpus Christi Urology Group LLC
state: Texas
city: Dallas
country: United States
facility: Urology Clinics of North Texas
state: Texas
city: San Antonio
country: United States
facility: Urology San Antonio Research
state: Texas
city: Fredericksburg
country: United States
facility: Mary Washington Hospital and Urology Associates of Fredericksburg
state: Virginia
city: Norfolk
country: United States
facility: Urology of Virginia, PC
state: Virginia
city: Virginia Beach
country: United States
facility: Urology of Virginia, PC
state: Virginia
city: Mountlake Terrace
country: United States
facility: Integrity Medical Research, LLC
state: Washington
city: Seattle
country: United States
facility: Seattle Urological Associates
state: Washington
Study officials:
affiliation: Spectrum Pharmaceuticals, Inc
name: Shanta Chawla, MD
role: STUDY_DIRECTOR
References: