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

Bladder Cancer Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01469221
• Other study ID #: SPI-1012
• Secondary ID: 2011-003517-42
• Status: Terminated
• Phase: Phase 3
• First received: November 8, 2011
• Last updated: December 13, 2017
• Start date: January 2012
• Est. completion date: April 2013

Study information

• Verified date: October 2017
• Source: Spectrum Pharmaceuticals, Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 47
• Est. completion date: April 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Bladder Cancer
• Urinary Bladder Neoplasms

Intervention

Drug:
• Apaziquone
6 weekly multi-instillation of Apaziquone 4 mg in 40 mL
• Placebo
6 weekly multi-instillation of matching placebo in 40mL

Locations

Country	Name	City	State
Czechia	Nemocnice Jablonec nad Nisou, Urologické oddelení	Jablonec nad Nisou
Czechia	Fakultní Thomayerova nemocnice s poliklinikou Urologické oddelení	Prague
Poland	Szpital Miejski im. Prof. E. Michalowskiego	Katowice
Poland	CenterMed Kraków sp z o.o.	Kraków
Poland	Niepubliczny Zaklad Opieki Zdrowotnej-Centrum Medyczne Szpital Swietej Rodziny sp z o.o.	Lódz
Poland	Wojewódzki Szpital Specjalistyczny im. Stefana Kardynala Wyszynskiego Samodzielny Publiczny Zaklad Opieki Zdrowotnej w Lublinie, Oddzial Urologii i Onkologii Urologicznej	Lublin
Poland	Nieubliczny Zaklad Opieki Zdrowotnej Europejskie Centrum Zdrowia Otwock im. Fryderyka Chopina Nieubliczny Zaklad Opieki Zdrowotnej	Otwock
Poland	Niepubliczny Zaklad Opieki Zdrowotnej Pabianickie Centrum Medyczne	Pabianice
Poland	Samodzielny Publiczny Zaklad Opieki Zdrowotnej, Wojewódzki Szpital Specjalistyczny nr 3	Rybnik
Poland	Wojewódzki Szpital Specjalistyczny W Siedlcach	Siedlce
Poland	Wojewódzki Szpital Specjalistyczny im Janusza Korczaka	Slupsk
Poland	Pomorska Akademia Medyczna	Szczecin
Poland	Centrum Medycznego Ksztalcenia Podyplomowego, Samodzielny Publiczny Szpital Kliniczny im. Prof. W. Orlowskiego	Warszawa
Poland	Miedzyleski Szpital Specjalistyczny w Warszawie Oddzial Urologii	Warszawa
Poland	Szpital Bielanski im. ks. J. Popieluszki Samodzielny Publiczny Zaklad Opieki Zdrowotnej	Warszawa
Poland	Szpital Kliniczny Dzieciatka Jezus - Centrum Leczenia Obrazen	Warszawa
Poland	Wojskowy Instytut Medyczny, Centralny Szpital Kliniczny MON	Warszawa
Poland	Wojewódzki Szpital Specjalistyczny we Wroclawiu, Osrodek Badawczo Rozwojowy	Wroclaw
Slovakia	Fakultná nemocnica s poliklinikou Žilina Urologické oddelenie	Žilina
Slovakia	Univerzitná nemocnica L. Pasteura Košice Univerzitná nemocnica L. Pasteura Košice	Košice
Slovakia	Univerzitná nemocnica Martin Urologická klinika	Martin
Slovakia	Fakultná nemocnica s poliklinikou J. A. Reimana Prešov Urologická klinika	Prešov
United States	Alliance Urology Specialists	Greensboro	North Carolina
United States	Tower Research Institute	Los Angeles	California
United States	Department of Urology, University of Miami Miller School of Medicine	Miami	Florida
United States	Associated Medical Professionals of New York, PLLC	Oneida	New York
United States	Somerset Urological Associates, PA	Somerville	New Jersey
United States	Male and Female Urology	Staten Island	New York
United States	Associated Medical Professionals of New York, PLLC	Syracuse	New York

Sponsors (2)

Lead Sponsor	Collaborator
Spectrum Pharmaceuticals, Inc	Allergan

Countries where clinical trial is conducted

United States,  Czechia,  Poland,  Slovakia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Recurrence	Time from randomization to the date of first histologically confirmed recurrence of bladder cancer	24 Months
Secondary	2-Year Recurrence Rate	Proportion of patients with recurrence at or before 24 months	24 Months