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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Allergan
Information provided by (Responsible Party):
Spectrum Pharmaceuticals, Inc
ClinicalTrials.gov Identifier:
NCT01469221
First received: November 8, 2011
Last updated: August 9, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
Bladder Cancer
Drug: Apaziquone
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Spectrum Pharmaceuticals, Inc:

Primary Outcome Measures:
  • Time to Recurrence [ Time Frame: Recurrence of Cancer in the Bladder in 24 Months Follow-up ] [ Designated as safety issue: No ]
    Time to recurrence (from randomization) for eligible patients with Low- intermediate risk NMIBC, who had undergone TURBT followed by, a single instillation of apaziquone immediately post TURBT and multiple instillations of apaziquone or placebo.


Secondary Outcome Measures:
  • Recurrence Rate at 24 Months [ Time Frame: 24 Months ] [ Designated as safety issue: No ]
  • Recurrence Rate at 12 Months [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
  • Time to Progression [ Time Frame: 24 Months after Randomization ] [ Designated as safety issue: No ]
  • Safety and Tolerability [ Time Frame: 24 Months after Randomization ] [ Designated as safety issue: Yes ]
    Safety and Tolerability will be mainly characterized by the number and severity of treatment emergent adverse events and treatment related AEs that occur or worsen after the first dose of study treatment.


Estimated Enrollment: 658
Study Start Date: July 2011
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Drug: Placebo
Matching placebo in 40mL diluent
Active Comparator: Apaziquone Drug: Apaziquone
Apaziquone 4 mg in 40 mL diluent
Other Names:
  • EoQuin
  • EO9

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01469221

Locations
United States, California
Tower Research Institute
Los Angeles, California, United States, 90048
United States, Florida
Department of Urology, University of Miami Miller School of Medicine
Miami, Florida, United States, 33136
United States, New Jersey
Somerset Urological Associates, PA
Somerville, New Jersey, United States, 08876
United States, New York
Associated Medical Professionals of New York, PLLC
Oneida, New York, United States, 13421
Male and Female Urology
Staten Island,, New York, United States, 10314
Associated Medical Professionals of New York, PLLC
Syracuse, New York, United States, 13210
United States, North Carolina
Alliance Urology Specialists
Greensboro, North Carolina, United States, 27403
Czech Republic
Nemocnice Jablonec nad Nisou, Urologické oddělení
Jablonec nad Nisou, Czech Republic, 466 60
Fakultní Thomayerova nemocnice s poliklinikou Urologické oddělení
Prague, Czech Republic, 14059
Poland
Szpital Miejski im. Prof. E. Michałowskiego
Katowice, Poland, 40-073
CenterMed Kraków sp z o.o.
Kraków, Poland, 31-530
Wojewódzki Szpital Specjalistyczny im. Stefana Kardynała Wyszyńskiego Samodzielny Publiczny Zakład Opieki Zdrowotnej w Lublinie, Oddział Urologii i Onkologii Urologicznej
Lublin, Poland, 20-718
Nieubliczny Zakład Opieki Zdrowotnej Europejskie Centrum Zdrowia Otwock im. Fryderyka Chopina Nieubliczny Zakład Opieki Zdrowotnej
Otwock, Poland, 05-400
Niepubliczny Zakład Opieki Zdrowotnej Pabianickie Centrum Medyczne
Pabianice, Poland, 95-200
Samodzielny Publiczny Zakład Opieki Zdrowotnej, Wojewódzki Szpital Specjalistyczny nr 3
Rybnik, Poland, 44-200
Wojewódzki Szpital Specjalistyczny W Siedlcach
Siedlce, Poland, 08-110
Pomorska Akademia Medyczna
Szczecin, Poland, 70-111
Wojewódzki Szpital Specjalistyczny im Janusza Korczaka
Słupsk, Poland, 76-200
Szpital Kliniczny Dzieciątka Jezus - Centrum Leczenia Obrażeń
Warszawa, Poland, 02-005
Wojskowy Instytut Medyczny, Centralny Szpital Kliniczny MON
Warszawa, Poland, 00-909
Międzyleski Szpital Specjalistyczny w Warszawie Oddział Urologii
Warszawa, Poland, 04-749
Centrum Medycznego Kształcenia Podyplomowego, Samodzielny Publiczny Szpital Kliniczny im. Prof. W. Orłowskiego
Warszawa, Poland, 00-416
Szpital Bielański im. ks. J. Popiełuszki Samodzielny Publiczny Zakład Opieki Zdrowotnej
Warszawa, Poland, 01-809
Wojewódzki Szpital Specjalistyczny we Wrocławiu, Ośrodek Badawczo Rozwojowy
Wrocław, Poland, 51-124
Niepubliczny Zakład Opieki Zdrowotnej-Centrum Medyczne Szpital Świętej Rodziny sp z o.o.
Łódź, Poland, 90-302
Slovakia
Univerzitná nemocnica L. Pasteura Košice Univerzitná nemocnica L. Pasteura Košice
Košice, Slovakia, 041 66
Univerzitná nemocnica Martin Urologická klinika
Martin, Slovakia, 036 59
Fakultná nemocnica s poliklinikou J. A. Reimana Prešov Urologická klinika
Prešov, Slovakia, 081 81
Fakultná nemocnica s poliklinikou Žilina Urologické oddelenie
Žilina, Slovakia, 012 07
Sponsors and Collaborators
Spectrum Pharmaceuticals, Inc
Allergan
Investigators
Study Director: Show-Li Sun, MD Spectrum Pharmaceuticals, Inc
  More Information

No publications provided

Responsible Party: Spectrum Pharmaceuticals, Inc
ClinicalTrials.gov Identifier: NCT01469221     History of Changes
Other Study ID Numbers: SPI-1012, 2011-003517-42
Study First Received: November 8, 2011
Last Updated: August 9, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Spectrum Pharmaceuticals, Inc:
Bladder Cancer
Non-Muscle Invasive Bladder Cancer
NMIBC
Apaziquone
EOquin
GU Cancer
TURBT

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Apaziquone
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 24, 2014