Single Dose Intravesical Apaziquone Postoperative in Patients Undergoing TURBT for Noninvasive Bladder Cancer (SPI-612)

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-612)

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): 812
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1R3S3
    • Centre Hospitalier Universitaire de Quebec
  • Alberta
    • Calgary, Alberta, Canada, T2V4R6
      • Prostate Cancer Institute
  • British Columbia
    • North Vancouver, British Columbia, Canada, V7L2P7
      • Lintor Medical, Inc.
    • Surrey, British Columbia, Canada, V3V1N1
      • Andreou Research
    • Victoria, British Columbia, Canada, V8T5G1
      • Can-Med Clinical Research, Inc
    • Victoria, British Columbia, Canada, V8V3N1
      • G. Steinhoff Clinical Research
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H2Y9
      • Queen Elizabeth II Health Sciences Centre
  • Ontario
    • Barrie, Ontario, Canada, L4M7G1
      • The Male/Female Health and Research Center - Royal Court Medical Centre
    • Brantford, Ontario, Canada, N3R4N3
      • Brantford Urology Research
    • Burlington, Ontario, Canada, L7N3V2
      • G. Kenneth Jansz Medicine Professional Corporation
    • Burlington, Ontario, Canada, L7S1V2
      • Urology Resource Centre
    • Kingston, Ontario, Canada, K7L3J7
      • Kingston General Hospital / Queen's University
    • Kitchener, Ontario, Canada, N2N2B9
      • Urology Associates, Urologic Medical Research
    • London, Ontario, Canada, N6A5W9
      • London Health Sciences Centre
    • Newmarket, Ontario, Canada, L3X1W1
      • Mor Urology, Inc.
    • North Bay, Ontario, Canada, P1B7K8
      • Dr. Bernard Goldfarb
    • North York, Ontario, Canada, M3B3S6
      • Stanley Flax Medical Professional Corporation
    • Oakville, Ontario, Canada, L6H3P1
      • The Fe/Male Health Centre
    • Orillia, Ontario, Canada, L3V7V1
      • Orillia Urology Associates
    • Oshawa, Ontario, Canada, L1H7K4
      • Urotec
    • Peterborough, Ontario, Canada, K9J7B3
      • ADA Medical Ltd.
    • Scarborough, Ontario, Canada, M1P2T7
      • AGT Research
    • Scarborough, Ontario, Canada, M1S4V5
      • Urology & Male Infertility
    • Toronto, Ontario, Canada, M4N3M5
      • Sunnybrook Health Sciences Centre
    • Toronto, Ontario, Canada, M4C5T2
      • Toronto East General Hospital
    • Toronto, Ontario, Canada, M5G2M9
      • University Health Network Princess Margaret Hospital
    • Toronto, Ontario, Canada, M6A3B5
      • The Male Health Centre
    • Toronto, Ontario, Canada, M6S4W4
      • Saint Joseph Health Center
  • Quebec
    • Laval, Quebec, Canada, H7G2E6
      • UroLaval
    • Montreal, Quebec, Canada, H3G1A4
      • McGill Urology Associates
    • Pointe Clare, Quebec, Canada, H9R4S3
      • Ultra-Med, Inc.
    • Sherbrooke, Quebec, Canada, J1H5N4
      • Centre Hospitalier Universitaire de Sherbrooke
• Poland
  • Białystok, Poland, 15-276
    • Uniwersytecki Szpital Kliniczny
  • Bielsko-Biała, Poland, 43-316
    • Szpital Wojewódzki w Bielsku-Białej
  • Gdańsk, Poland, 80-402
    • Akademickie Centrum Kliniczne - Szpital Akademii Medycznej W Gdansku
  • Inowrocław, Poland, 88-100
    • Publiczny Specjalistyczny Zakład Opieki Zdrowotnej w Inowrocławiu
  • Katowice, Poland, 40-073
    • Szpital Miejski im. Prof. E. Michałowskiego
  • Kielce, Poland, 25-734
    • Świętokrzyskie Centrum Onkologii, Samodzielny Publiczny Zakład Opieki Zdrowotnej
  • Kościerzyna, Poland, 83-400
    • Szpital Specjalistyczny w Kościerzynie
  • Kraków, Poland, 30-017
    • Niepubliczny Zakład Opieki Zdrowotnej "Racławicka"
  • Lublin, Poland, 20-954
    • Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie
  • Pabianice, Poland, 95-200
    • Samodzielny Publiczny Zakład Opieki Zdrowotnej w Pabianicach
  • Poznań, Poland, 61-285
    • Zakład Opieki Zdrowotnej Poznań - Stare Miasto
  • Pruszków, Poland, 05-800
    • Szpital Kolejowy im. Dr med.. Włodzimierza Roeflera w Pruszkowie
  • Rybnik, Poland, 44-200
    • Samodzielny Publiczny Zakład Opieki Zdrowotnej, Wojewódzki Szpital Specjalistyczny nr 3
  • Siedlce, Poland, 08-110
    • Wojewodzki Szpital Specjalistyczny w Siedlcach
  • Szczecin, Poland, 70-111
    • Pomorska Akademia Medyczna
  • Słupsk, Poland, 76-200
    • Wojewódzki Szpital Specjalistyczny im Janusza Korczaka
  • Warszawa, Poland, 00-416
    • Centrum Medycznego Kształcenia Podyplomowego, Samodzielny Publiczny Szpital Kliniczny im. Prof. W. Orłowskiego
  • Warszawa, Poland, 00-909
    • Wojskowy Instytut Medyczny, Centralny Szpital Kliniczny MON
  • Warszawa, Poland, 02-005
    • Szpital Kliniczny Dzieciatka Jezus - Centrum Leczenia Obrazen
  • Warszawa, Poland, 02-781
    • Centrum Onkologii im. Marii Skodowskiej-Curie
  • Warszawa, Poland, 04-749
    • Fundacja "Urologia", Międzyleski Szpital Specjalistyczny w Warszawie
  • Wrocław, Poland, 50-556
    • Akademicki Szpital Kliniczny im Jana Mikulicza-Radeckiego we Wrocławiu
  • Wrocław, Poland, 51-124
    • Wojewódzki Szpital Specjalistyczny we Wrocławiu, Ośrodek Badawczo Rozwojowy
  • Łódź, Poland, 90-549
    • Uniwersytecki Szpital Kliniczny nr 2 Wojskowej Akademii Medycznej Uniwersytetu Medycznego w Łodzi - Centralny Szpital Weteranów
• United States
  • California
    • Anaheim, California, United States, 92801
      • Advanced Urology Medical Center Clinical Trials
  • Florida
    • West Palm Beach, Florida, United States, 33407
      • Hal J. Bashein, D.O.
  • Georgia
    • Marietta, Georgia, United States, 30060
      • Urology Enterprises
    • Roswell, Georgia, United States, 30076
      • North Fulton Urology
  • Illinois
    • Hines, Illinois, United States, 60141
      • Hines VA Hospital
  • Louisiana
    • Slidell, Louisiana, United States, 70458
      • The Urology Center
  • Maryland
    • Baltimore, Maryland, United States, 21237
      • Chesapeake Urology Research Associates
    • Towson, Maryland, United States, 21204
      • Chesapeake Urology Research Associates
  • Michigan
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital
  • New Jersey
    • Hillsborough, New Jersey, United States, 08844
      • PharmaTrials, Inc. - Male & Female Urology
    • Hillsborough, New Jersey, United States, 08844
      • PharmaTrials, Inc.
  • New York
    • Bay Shore, New York, United States, 11706
      • Medical & Clinical Research Associates, LLC
    • Manhasset, New York, United States, 11030
      • Urology Associates, PC
    • New Hyde Park, New York, United States, 11040
      • North Shore - LIJ Health System - The Arthur Smith Institute for Urology
  • North Carolina
    • Greensboro, North Carolina, United States, 27403
      • Alliance Urology Specialists
    • Winston-Salem, North Carolina, United States, 27103
      • Piedmont Medical Research
  • Pennsylvania
    • Bryn Mawr, Pennsylvania, United States, 19010
      • Center for Urologic Care
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina, Dept. of Urology
  • Texas
    • McAllen, Texas, United States, 78503
      • Urology Associates of South Texas
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Salt Lake Research
  • Virginia
    • Alexandria, Virginia, United States, 22304
      • Adult and Pediatric Urologists

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 of the following questions must be answered "Yes" in order for the patient to participate in the study.

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

Exclusion Criteria:

All of the following questions must be answered "No" in order for the patient to participate in the study.

1. Does the patient have more than 5 bladder tumors?
2. Does any single bladder tumor exceed 3.5 cm in diameter?
3. Does the patient have a single, primary bladder tumor <0.5 cm and has no previous diagnosis of bladder cancer?
4. Has the patient ever received EOquin(r)?
5. Does the patient have, or has the patient ever had, any bladder tumor known to be other than tumor Ta or grade G1 or G2 (low grade [WHO/ISUP classification])?
6. Does the patient have, or has the patient ever had any bladder tumor with histology other than transitional cell carcinoma?
7. Does the patient have, or has the patient ever had, carcinoma in situ (CIS)?
8. Does the patient have an active urinary tract infection?
9. Does the patient have a bleeding disorder or a screening platelet count < 100 x 109/L?
10. Does the patient have any unstable medical condition that would make it unsafe for him/her to undergo TURBT under general or spinal anesthesia?
11. Does the patient have screening hemoglobin < 10 mg/dL, a screening absolute neutrophil count < 1.5 x 109/L?
12. Does the patient have a known immunodeficiency disorder?
13. Has the patient received any investigational treatment within the past 30 days?
14. Is the patient breast feeding?
15. Does the patient have a history of interstitial cystitis?
16. Does the patient have a history of allergy to red color food dye?
17. 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
Overall Survival	The number of months from randomization to death from any cause.	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

Collaborators and Investigators

• Sponsor: Spectrum Pharmaceuticals, Inc

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: January 11, 2008
• First Submitted That Met QC Criteria: January 22, 2008
• First Posted (Estimate): January 23, 2008

Study Record Updates

• Last Update Posted (Actual): November 13, 2017
• Last Update Submitted That Met QC Criteria: October 10, 2017
• Last Verified: October 1, 2017

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-612