Clinical trial NCT01469221: Efficacy and Safety Study of Apaziquone vs. Placebo in Patients With Non-Muscle Invasive Bladder Cancer (NMIBC)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Bladder Cancer
Keywords: Bladder Cancer
Non-Muscle Invasive Bladder Cancer
NMIBC
Apaziquone
EOquin
GU Cancer
TURBT
Lead sponsor: Spectrum Pharmaceuticals, Inc
Sponsor class: INDUSTRY
Collaborators: name: Allergan
First posted: 2011-11-10
Enrollment: 47
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 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.


Eligibility criteria: 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

Primary outcomes:
measure: Time to Recurrence
timeFrame: 24 Months
Secondary outcomes:
measure: 2-Year Recurrence Rate
timeFrame: 24 Months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Tower Research Institute
state: California
city: Miami
country: United States
facility: Department of Urology, University of Miami Miller School of Medicine
state: Florida
city: Somerville
country: United States
facility: Somerset Urological Associates, PA
state: New Jersey
city: Oneida
country: United States
facility: Associated Medical Professionals of New York, PLLC
state: New York
city: Staten Island
country: United States
facility: Male and Female Urology
state: New York
city: Syracuse
country: United States
facility: Associated Medical Professionals of New York, PLLC
state: New York
city: Greensboro
country: United States
facility: Alliance Urology Specialists
state: North Carolina
city: Jablonec nad Nisou
country: Czechia
facility: Nemocnice Jablonec nad Nisou, Urologické oddělení
city: Prague
country: Czechia
facility: Fakultní Thomayerova nemocnice s poliklinikou Urologické oddělení
city: Katowice
country: Poland
facility: Szpital Miejski im. Prof. E. Michałowskiego
city: Kraków
country: Poland
facility: CenterMed Kraków sp z o.o.
city: Lublin
country: Poland
facility: Wojewódzki Szpital Specjalistyczny im. Stefana Kardynała Wyszyńskiego Samodzielny Publiczny Zakład Opieki Zdrowotnej w Lublinie, Oddział Urologii i Onkologii Urologicznej
city: Otwock
country: Poland
facility: Nieubliczny Zakład Opieki Zdrowotnej Europejskie Centrum Zdrowia Otwock im. Fryderyka Chopina Nieubliczny Zakład Opieki Zdrowotnej
city: Pabianice
country: Poland
facility: Niepubliczny Zakład Opieki Zdrowotnej Pabianickie Centrum Medyczne
city: Rybnik
country: Poland
facility: Samodzielny Publiczny Zakład Opieki Zdrowotnej, Wojewódzki Szpital Specjalistyczny nr 3
city: Siedlce
country: Poland
facility: Wojewódzki Szpital Specjalistyczny W Siedlcach
city: Szczecin
country: Poland
facility: Pomorska Akademia Medyczna
city: Słupsk
country: Poland
facility: Wojewódzki Szpital Specjalistyczny im Janusza Korczaka
city: Warszawa
country: Poland
facility: Centrum Medycznego Kształcenia Podyplomowego, Samodzielny Publiczny Szpital Kliniczny im. Prof. W. Orłowskiego
city: Warszawa
country: Poland
facility: Wojskowy Instytut Medyczny, Centralny Szpital Kliniczny MON
city: Warszawa
country: Poland
facility: Szpital Bielański im. ks. J. Popiełuszki Samodzielny Publiczny Zakład Opieki Zdrowotnej
city: Warszawa
country: Poland
facility: Szpital Kliniczny Dzieciątka Jezus - Centrum Leczenia Obrażeń
city: Warszawa
country: Poland
facility: Międzyleski Szpital Specjalistyczny w Warszawie Oddział Urologii
city: Wrocław
country: Poland
facility: Wojewódzki Szpital Specjalistyczny we Wrocławiu, Ośrodek Badawczo Rozwojowy
city: Łódź
country: Poland
facility: Niepubliczny Zakład Opieki Zdrowotnej-Centrum Medyczne Szpital Świętej Rodziny sp z o.o.
city: Košice
country: Slovakia
facility: Univerzitná nemocnica L. Pasteura Košice Univerzitná nemocnica L. Pasteura Košice
city: Martin
country: Slovakia
facility: Univerzitná nemocnica Martin Urologická klinika
city: Prešov
country: Slovakia
facility: Fakultná nemocnica s poliklinikou J. A. Reimana Prešov Urologická klinika
city: Žilina
country: Slovakia
facility: Fakultná nemocnica s poliklinikou Žilina Urologické oddelenie
Study officials:
affiliation: Spectrum Pharmaceuticals, Inc
name: Show-Li Sun, MD
role: STUDY_DIRECTOR
References: