Efficacy and Safety Study of Apaziquone vs. Placebo in Patients With Non-Muscle Invasive Bladder Cancer (NMIBC)

A Phase 3 International, Double-Bind Trial Evaluating Efficacy and Safety of Multiple Instillations of Intravesical Apaziquone vs. Placebo in Patients With Low-Intermediate Risk Non-Muscle Invasive Bladder Cancer (NMIBC)

This is an international, multicenter, double-blind, placebo-controlled, randomized study. All eligible patients entering the open label phase of the study will receive a single immediate instillation of apaziquone (4 mg in 40 mL diluent), post transurethral resection-bladder tumor (TURBT). Following Central Pathology review of histology and Double Blind Phase qualification, patients with confirmed eligibility will be randomized to receive either 6 weekly intravesical instillations of apaziquone or matching placebo and undergo cystoscopic and safety assessments every 3 months for 24 months. Patients with histologic evidence of recurrent disease during the study will be treated according to current treatment guidelines or local standard of care. Safety and efficacy assessments will be performed at 3 month intervals for all randomized patients throughout the study. Patients who receive single dose of apaziquone immediately following TURBT and are not eligible for randomization will be followed for 3 months by cystoscopic exam and safety assessments.

Study Overview

• Status: Terminated
• Conditions: Bladder Cancer
• Intervention / Treatment: Drug: Apaziquone; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 3

Contacts and Locations

Study Locations

• Czechia
  • Jablonec nad Nisou, Czechia, 466 60
    • Nemocnice Jablonec nad Nisou, Urologické oddělení
  • Prague, Czechia, 14059
    • Fakultní Thomayerova nemocnice s poliklinikou Urologické oddělení
• Poland
  • Katowice, Poland, 40-073
    • Szpital Miejski im. Prof. E. Michałowskiego
  • Kraków, Poland, 31-530
    • CenterMed Kraków sp z o.o.
  • Lublin, Poland, 20-718
    • Wojewódzki Szpital Specjalistyczny im. Stefana Kardynała Wyszyńskiego Samodzielny Publiczny Zakład Opieki Zdrowotnej w Lublinie, Oddział Urologii i Onkologii Urologicznej
  • Otwock, Poland, 05-400
    • Nieubliczny Zakład Opieki Zdrowotnej Europejskie Centrum Zdrowia Otwock im. Fryderyka Chopina Nieubliczny Zakład Opieki Zdrowotnej
  • Pabianice, Poland, 95-200
    • Niepubliczny Zakład Opieki Zdrowotnej Pabianickie Centrum Medyczne
  • 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, 01-809
    • Szpital Bielański im. ks. J. Popiełuszki Samodzielny Publiczny Zakład Opieki Zdrowotnej
  • Warszawa, Poland, 04-749
    • Międzyleski Szpital Specjalistyczny w Warszawie Oddział Urologii
  • Wrocław, Poland, 51-124
    • Wojewódzki Szpital Specjalistyczny we Wrocławiu, Ośrodek Badawczo Rozwojowy
  • Łódź, Poland, 90-302
    • Niepubliczny Zakład Opieki Zdrowotnej-Centrum Medyczne Szpital Świętej Rodziny sp z o.o.
• Slovakia
  • Košice, Slovakia, 041 66
    • Univerzitná nemocnica L. Pasteura Košice Univerzitná nemocnica L. Pasteura Košice
  • Martin, Slovakia, 036 59
    • Univerzitná nemocnica Martin Urologická klinika
  • Prešov, Slovakia, 081 81
    • Fakultná nemocnica s poliklinikou J. A. Reimana Prešov Urologická klinika
  • Žilina, Slovakia, 012 07
    • Fakultná nemocnica s poliklinikou Žilina Urologické oddelenie
• United States
  • California
    • Los Angeles, California, United States, 90048
      • Tower Research Institute
  • Florida
    • Miami, Florida, United States, 33136
      • Department of Urology, University of Miami Miller School of Medicine
  • New Jersey
    • Somerville, New Jersey, United States, 08876
      • Somerset Urological Associates, PA
  • New York
    • Oneida, New York, United States, 13421
      • Associated Medical Professionals of New York, PLLC
    • Staten Island, New York, United States, 10314
      • Male and Female Urology
    • Syracuse, New York, United States, 13210
      • Associated Medical Professionals of New York, PLLC
  • North Carolina
    • Greensboro, North Carolina, United States, 27403
      • Alliance Urology Specialists

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 (for Open Label):

1. Has the patient given written informed consent and is the patient willing and able to abide by the protocol?
2. Is the patient 18 years old or above?
3. If the patient is a female of childbearing potential, is she using an acceptable/effective method of contraception?
4. Does the female patient of childbearing potential have a negative serum pregnancy test at screening?

5. Does the patient with clinically apparent primary or recurrent low grade Ta NMIBC have :

   • multiple tumors (2-7)
   • No single Tumor > 3 cm
   • No history / evidence of Tis

   Or does the patient with clinically apparent primary or recurrent high grade Ta NMIBC have:

   • A single tumor that is ≤ 3 cm
   • No history / evidence of Tis
6. Is the patient able to retain bladder instillations for a minimum of 60 minutes (± 6 minutes)?
7. Did the patient have upper urinary tract evaluation to exclude urothelial carcinoma, hydronephrosis or renal cell carcinoma or other renal cancers in the 6 months prior to study screening?
8. Is patient's urethra (including prostatic urethra in men) endoscopically free of any visible TCC?
9. For patients with recurrent tumor, did the patient have at least a 6-month cystoscopically-confirmed tumor-free interval between the last tumor recurrence and the time of screening?
10. Has the male patient with a prostate specific antigen (PSA) between 4 and 10 ng/mL had a diagnostic evaluation that reasonably excludes the diagnosis of prostate cancer in the opinion of the Investigator?

Exclusion Criteria (for Open Label):

1. Has the patient received any previous pelvic radiotherapy (includes external beam and/or brachytherapy)?
2. Has the patient ever received apaziquone?
3. Has the patient received an induction course (completed 5 of 6 scheduled weekly instillations) of intravesical BCG (± interferon) with the last dose given less than 12 months ago?
4. Has the patient had any prior intravesical chemotherapy, exclusive of single-dose adjuvant intravesical chemotherapy immediately post-TURBT?
5. Does the patient have a history of urinary retention or a post void residual ≥ 250 cc by bladder scan or ultrasound (post void residual test may be repeated up to 3 times)?
6. Does the patient have or has the patient had any bladder tumor with histology other than transitional cell carcinoma?
7. Does the patient have or has the patient had micro-papillary transitional cell carcinoma?
8. If the patient has recurrent papillary disease of the bladder, has the pathology been anything other than pTa in the past?
9. Does the patient have an active urinary tract infection confirmed by culture or a documented history of recurrent UTI (≥ 6 for females and ≥2 for males per year) in the prior 2 years?
10. Does the patient have a bleeding disorder or a screening platelet count < 50 x 109/L?
11. Does the patient have a screening hemoglobin < 10 g/dL?
12. Does the male patient have a screening serum PSA > 10 ng/mL?
13. Does the patient have a history of Acquired Immunodeficiency Syndrome or HIV positive?
14. Does the patient have a condition or a concurrent severe and/or uncontrolled medical or psychiatric disease (e.g., uncontrolled diabetes, decompensated congestive heart failure, myocardial infarction within 6 months of study, unstable and uncontrolled hypertension, or an active uncontrolled infection), which could compromise participation, compliance with scheduled visits and/or completion of the study?
15. Has the patient participated in an investigational protocol within the past 90 days?
16. Is the patient pregnant or breast feeding?
17. Does the patient have a life expectancy of <3 years?

18. Has the patient had any other malignancy or received therapy for any malignancy in the last five years except

    • non-melanoma skin tumors
    • stage 0 (in situ) cervical carcinoma
    • undetectable PSA for ≥1 year following definitive therapy for localized prostate cancer?
19. Does the patient have documented vesicoureteral reflux or an indwelling ureteral stent?
20. Does the patient have tumor in a bladder diverticulum?
21. Does the patient have a known allergy to red color food dye?

Double-Blind Phase Inclusion Criteria

1. Was all visible tumor resected at the initial TURBT?

2. Does Central Pathology review of the patient's bladder tumor confirm:

   • Low grade Ta disease for multiple tumors (2 - 7) or
   • High Grade Ta disease for single tumor
   • No microscopic evidence of lymphovascular invasion and/or evidence of tumor thromboemboli

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; Apaziquone (4 mg in 40 mL)	Drug: Apaziquone; 6 weekly multi-instillation of Apaziquone 4 mg in 40 mL; Other Names: EoQuin; EO9
Placebo Comparator: Placebo; Matching placebo (40 mL)	Drug: Placebo; 6 weekly multi-instillation of matching placebo in 40mL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Recurrence	Time from randomization to the date of first histologically confirmed recurrence of bladder cancer	24 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2-Year Recurrence Rate	Proportion of patients with recurrence at or before 24 months	24 Months

Collaborators and Investigators

• Sponsor: Spectrum Pharmaceuticals, Inc
• Collaborators: Allergan
• Investigators: Study Director: Show-Li Sun, MD, Spectrum Pharmaceuticals, Inc

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2012
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: November 8, 2011
• First Submitted That Met QC Criteria: November 9, 2011
• First Posted (Estimate): November 10, 2011

Study Record Updates

• Last Update Posted (Actual): December 15, 2017
• Last Update Submitted That Met QC Criteria: December 13, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: NMIBC; Bladder Cancer; Non-Muscle Invasive Bladder Cancer; TURBT; Apaziquone; EOquin; GU 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-1012; 2011-003517-42 (EudraCT Number)