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

NCT ID: NCT01469221

Last Updated: 2017-12-15

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 47 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-01-31
• Study Completion Date: 2013-04-30

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.

Conditions

Bladder Cancer

Keywords

Bladder Cancer; Non-Muscle Invasive Bladder Cancer; NMIBC; Apaziquone; EOquin; GU Cancer; TURBT

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Apaziquone

Apaziquone (4 mg in 40 mL)

Group Type: EXPERIMENTAL

Apaziquone

Intervention Type: DRUG

6 weekly multi-instillation of Apaziquone 4 mg in 40 mL

Placebo

Matching placebo (40 mL)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

6 weekly multi-instillation of matching placebo in 40mL

Interventions

Apaziquone

6 weekly multi-instillation of Apaziquone 4 mg in 40 mL

Intervention Type: DRUG

Placebo

6 weekly multi-instillation of matching placebo in 40mL

Intervention Type: DRUG

Other Intervention Names

EoQuin; EO9

Eligibility Criteria

Inclusion Criteria

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?

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

Exclusion Criteria

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?

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Allergan

INDUSTRY

Sponsor Role: collaborator

Spectrum Pharmaceuticals, Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Show-Li Sun, MD

Role: STUDY_DIRECTOR

Spectrum Pharmaceuticals, Inc

Locations

Tower Research Institute

Los Angeles, California, United States

Department of Urology, University of Miami Miller School of Medicine

Miami, Florida, United States

Somerset Urological Associates, PA

Somerville, New Jersey, United States

Associated Medical Professionals of New York, PLLC

Oneida, New York, United States

Male and Female Urology

Staten Island, New York, United States

Associated Medical Professionals of New York, PLLC

Syracuse, New York, United States

Alliance Urology Specialists

Greensboro, North Carolina, United States

Nemocnice Jablonec nad Nisou, Urologické oddělení

Jablonec nad Nisou, , Czechia

Fakultní Thomayerova nemocnice s poliklinikou Urologické oddělení

Prague, , Czechia

Szpital Miejski im. Prof. E. Michałowskiego

Katowice, , Poland

CenterMed Kraków sp z o.o.

Krakow, , Poland

Niepubliczny Zakład Opieki Zdrowotnej-Centrum Medyczne Szpital Świętej Rodziny sp z o.o.

Lodz, , Poland

Wojewódzki Szpital Specjalistyczny im. Stefana Kardynała Wyszyńskiego Samodzielny Publiczny Zakład Opieki Zdrowotnej w Lublinie, Oddział Urologii i Onkologii Urologicznej

Lublin, , Poland

Nieubliczny Zakład Opieki Zdrowotnej Europejskie Centrum Zdrowia Otwock im. Fryderyka Chopina Nieubliczny Zakład Opieki Zdrowotnej

Otwock, , Poland

Niepubliczny Zakład Opieki Zdrowotnej Pabianickie Centrum Medyczne

Pabianice, , Poland

Samodzielny Publiczny Zakład Opieki Zdrowotnej, Wojewódzki Szpital Specjalistyczny nr 3

Rybnik, , Poland

Wojewódzki Szpital Specjalistyczny W Siedlcach

Siedlce, , Poland

Pomorska Akademia Medyczna

Szczecin, , Poland

Wojewódzki Szpital Specjalistyczny im Janusza Korczaka

Słupsk, , Poland

Centrum Medycznego Kształcenia Podyplomowego, Samodzielny Publiczny Szpital Kliniczny im. Prof. W. Orłowskiego

Warsaw, , Poland

Wojskowy Instytut Medyczny, Centralny Szpital Kliniczny MON

Warsaw, , Poland

Szpital Bielański im. ks. J. Popiełuszki Samodzielny Publiczny Zakład Opieki Zdrowotnej

Warsaw, , Poland

Szpital Kliniczny Dzieciątka Jezus - Centrum Leczenia Obrażeń

Warsaw, , Poland

Międzyleski Szpital Specjalistyczny w Warszawie Oddział Urologii

Warsaw, , Poland

Wojewódzki Szpital Specjalistyczny we Wrocławiu, Ośrodek Badawczo Rozwojowy

Wroclaw, , Poland

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, , Slovakia

Fakultná nemocnica s poliklinikou Žilina Urologické oddelenie

Žilina, , Slovakia

Countries

United States; Czechia; Poland; Slovakia

Other Identifiers

2011-003517-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

SPI-1012

Identifier Type: -

Identifier Source: org_study_id