Efficacy and Safety of Multi-Instillations of Apaziquone in Patients With Non-Muscle Invasive Bladder Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Allergan
Information provided by (Responsible Party):
Spectrum Pharmaceuticals, Inc
ClinicalTrials.gov Identifier:
NCT01410565
First received: August 1, 2011
Last updated: August 9, 2013
Last verified: August 2013

August 1, 2011
August 9, 2013
July 2011
December 2014   (final data collection date for primary outcome measure)
Time to Recurrence [ Time Frame: Recurrence of cancer in the bladder during 24 months of 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.
Same as current
Complete list of historical versions of study NCT01410565 on ClinicalTrials.gov Archive Site
  • 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 from 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.
Same as current
Not Provided
Not Provided
 
Efficacy and Safety of Multi-Instillations of Apaziquone in Patients With Non-Muscle Invasive Bladder Cancer
A Phase 3 International, Multicenter, Double-Blind, Placebo-Controlled, Randomized Trial Evaluating the 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 from randomization. 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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Bladder Cancer
  • Drug: Apaziquone
    Apaziquone 4 mg in 40 mL diluent
    Other Names:
    • EO9
    • EOquin
  • Drug: Placebo
    Placebo for Double Blind Phase
  • Active Comparator: Apaziquone
    Intervention: Drug: Apaziquone
  • Placebo Comparator: Placebo
    Placebo
    Intervention: Drug: Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
658
December 2015
December 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

Open Phase 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?
  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?

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

Exclusion Criteria:

Open Phase 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 mg/dL?
  12. Does the male patient have a 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?
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
NCT01410565
SPI-1011
No
Spectrum Pharmaceuticals, Inc
Spectrum Pharmaceuticals, Inc
Allergan
Study Director: Show-Li Sun, MD Spectrum Pharmaceuticals, Inc
Spectrum Pharmaceuticals, Inc
August 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP