Single Dose Intravesical Apaziquone Postoperative in Patients Undergoing TURBT for Noninvasive Bladder Cancer (SPI-611)

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)

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.

Study Overview

• Status: Completed
• Conditions: Bladder Cancer
• Intervention / Treatment: Drug: Apaziquone; Procedure: TURBT; Drug: 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.

• Study Type: Interventional
• Enrollment (Actual): 802
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alaska
    • Anchorage, Alaska, United States, 99508
      • Alaska Clinical Research Center, LLC
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • BCG Oncology
    • Sun City, Arizona, United States, 85032
      • Sun Health Research Institute
  • California
    • Burbank, California, United States, 91505
      • Urology Associates Medical Group
    • Fresno, California, United States, 93720
      • Urology Associates of Central CA
    • Laguna Woods, California, United States, 92653
      • South Orange County Medical Research Center
    • Los Angeles, California, United States, 90027
      • Kaiser Permanente Los Angeles Medical Center
    • Orange, California, United States, 92868
      • Cancer Research Dept/St. Joseph Hospital
    • San Bernardino, California, United States, 92404
      • San Bernardino Urologic Association
    • San Francisco, California, United States, 94121
      • VA Medical Center
  • Colorado
    • Denver, Colorado, United States, 80211
      • The Urology Center of Colorado
  • Connecticut
    • Middlebury, Connecticut, United States, 06762
      • Connecticut Clinical Research Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20006
      • Urologic Surgeons of Washington
  • Florida
    • Lakeland, Florida, United States, 33805
      • Lakeland Regional Cancer Center
    • Longwood, Florida, United States, 32750
      • Urology Consultants
    • Miami, Florida, United States, 33136
      • University of Miami
    • New Port Richey, Florida, United States, 34652
      • Advanced Research Institute
    • New Port Richey, Florida, United States, 34655
      • Advanced Research Institute
    • Ocala, Florida, United States, 34474
      • Florida Foundation for Healthcare Research
    • Sarasota, Florida, United States, 34237
      • Florida Urology Specialists
    • Tallahassee, Florida, United States, 32308
      • Southeastern Research Group, Inc.
  • Georgia
    • Gainesville, Georgia, United States, 30501
      • Gainesville Urology, PC
    • Macon, Georgia, United States, 31217
      • Urological Professional Association
  • Idaho
    • Coeur d'Alene, Idaho, United States, 83814
      • North Idaho Urology
    • Meridian, Idaho, United States, 83642
      • Idaho Urologic Institute, P.A.
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
    • Mattoon, Illinois, United States, 61938
      • Urology Associates, SC
    • Peoria, Illinois, United States, 61614
      • Speciality Care Research
  • Indiana
    • Fort Wayne, Indiana, United States, 46825
      • Northeast Indiana Research, LLC
    • Jeffersonville, Indiana, United States, 47130
      • Metropolitan Urology
  • Kansas
    • Overland Park, Kansas, United States, 66211
      • Kansas City Urology Care, P.A.
  • Louisiana
    • Shreveport, Louisiana, United States, 71106
      • Regional Urology, LLC
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • Anne Arundel Urology
    • Greenbelt, Maryland, United States, 20770
      • Myron Murdock, MD, LLC
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • MMPC Urology
    • Saint Joseph, Michigan, United States, 49085
      • Lakeside Urology, PC
    • Troy, Michigan, United States, 48084
      • Michigan Institute of Urology, PC
  • Montana
    • Missoula, Montana, United States, 59802
      • Five Valleys Urology
  • New Jersey
    • Brick, New Jersey, United States, 08724
      • Coastal Urological Associates, PA
    • Lawrenceville, New Jersey, United States, 08648
      • AdvanceMed Research
    • Marlton, New Jersey, United States, 08053
      • Delaware Valley Urology, LLC-Marlton
    • Sewell, New Jersey, United States, 08080
      • Deleware Valley Urology, LLC-Washington Township
    • Voorhees, New Jersey, United States, 08043
      • Delaware Valley Urology, LLC - Voorhees
    • Westampton, New Jersey, United States, 08060
      • Delaware Valley Urology, LLC-Westampton
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Urology Group of New Mexico
  • New York
    • Albany, New York, United States, 12208
      • Capital Region Urological Surgeons
    • Albany, New York, United States, 12208
      • The Urological Institute of NE NY
    • Carmel, New York, United States, 10512
      • Adult and Pediatric Urology
    • Garden City, New York, United States, 11530
      • AccuMed Research Associates
    • Garden City, New York, United States, 11530
      • Urological Surgeons of Long Island, P.C.
    • Kingston, New York, United States, 12401
      • Hudson Valley Urology, PC
    • New York, New York, United States, 10016
      • University Urology Associates
    • Oneida, New York, United States, 13421
      • CNY Urology, PC
    • Poughkeepsie, New York, United States, 12601
      • Hudson Valley Urology
    • Rochester, New York, United States, 14618
      • Urology Associates of Rochester, LLC
    • Williamsville, New York, United States, 14221
      • Center for Urologic Research of WNY, LLC
  • Ohio
    • Cincinnati, Ohio, United States, 45212
      • TriState Urologic Services PSC, Inc.
    • Columbus, Ohio, United States, 43220
      • Columbus Urology Research, LLC
  • Oregon
    • Springfield, Oregon, United States, 97477
      • Oregon Urology Institute
  • Pennsylvania
    • Bala-Cynwyd, Pennsylvania, United States, 19026
      • Urologic Consultants of South Eastern Pennsylvania
    • Lancaster, Pennsylvania, United States, 17604
      • Urological Associates of Lancaster
    • Philadelphia, Pennsylvania, United States, 19111-2497
      • Fox Chase Cancer Center
    • Pittsburgh, Pennsylvania, United States, 15212
      • Triangle Urology Group
    • Williamsport, Pennsylvania, United States, 17701
      • Susquehenna Urology
  • South Carolina
    • Myrtle Beach, South Carolina, United States, 29572
      • Carolina Urologic Research Center
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • The Conrad Pearson Clinic
  • Texas
    • Corpus Christi, Texas, United States, 78404
      • Corpus Christi Urology Group LLC
    • Dallas, Texas, United States, 75231
      • Urology Clinics of North Texas
    • San Antonio, Texas, United States, 78229
      • Urology San Antonio Research
  • Virginia
    • Fredericksburg, Virginia, United States, 22401
      • Mary Washington Hospital and Urology Associates of Fredericksburg
    • Norfolk, Virginia, United States, 23502
      • Urology of Virginia, PC
    • Virginia Beach, Virginia, United States, 23454
      • Urology of Virginia, PC
  • Washington
    • Mountlake Terrace, Washington, United States, 98043
      • Integrity Medical Research, LLC
    • Seattle, Washington, United States, 98104
      • Seattle Urological Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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?

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Apaziquone; TURBT + a single intravesical dose of Apaziquone 4mg in 40ml instilled into the bladder post-TURBT	Drug: Apaziquone; A single intravesical dose of Apaziquone 4mg in 40ml instilled into the bladder post-TURBT; Other Names: EOquin®, Qapzola; Procedure: TURBT; TransUrethral Resection of the Bladder Tumor
Placebo Comparator: Placebo; TURBT + a single intravesical dose of placebo instilled into the bladder post-TURBT	Procedure: TURBT; TransUrethral Resection of the Bladder Tumor; Drug: Placebo; A single intravesical dose of placebo instilled into the bladder post-TURBT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence Rate at 2 Years	The percentage of participants with histologically confirmed recurrence of the bladder tumor at any time after randomization and on or before year 2.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Recurrence	The number of months from randomization to histologically confirmed recurrence of the patient's bladder tumor.	2 years
Progression Rate at 2 Years	The percentage of participants that progress to either a higher stage or grade from the histologically confirmed stage and grade at time of randomization.	2 years
Time to Progression	The number of months from randomization to progression to either a higher stage or grade of the patient's bladder tumor.	2 years
Number of Recurrences Per Patient	The number of histologically confirmed recurrences during the course of the study.	2 years
Disease Free Interval	The number of months from randomization to histologically confirmed progression of the patient's bladder tumor or death from any cause	2 years
Disease Free Survival	The number of months from randomization to histologically confirmed recurrence of the patient's bladder tumor or death from any cause	2 years
Overall Survival	The number of months from randomization to death from any cause.	2 years

Collaborators and Investigators

• Sponsor: Spectrum Pharmaceuticals, Inc

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2007
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): January 1, 2012

Study Registration Dates

• First Submitted: April 16, 2007
• First Submitted That Met QC Criteria: April 17, 2007
• First Posted (Estimate): April 18, 2007

Study Record Updates

• Last Update Posted (Actual): March 30, 2021
• Last Update Submitted That Met QC Criteria: March 9, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Noninvasive Bladder Cancer
• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Urinary Bladder Neoplasms; Antineoplastic Agents; Apaziquone
• Other Study ID Numbers: SPI-611