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)
Overview
- Phase
- Phase 3
- Intervention
- Apaziquone
- Conditions
- Bladder Cancer
- Sponsor
- Spectrum Pharmaceuticals, Inc
- Enrollment
- 66
- Locations
- 47
- Primary Endpoint
- Time to Recurrence
- Status
- Terminated
- Last Updated
- 9 years ago
Overview
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 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Open Phase Inclusion Criteria:
- •Has the patient given written informed consent and is the patient willing and able to abide by the protocol?
- •Is the patient 18 years old or above?
- •If the patient is a female of childbearing potential, is she using an acceptable/effective method of contraception?
- •Does the female patient of childbearing potential have a negative serum pregnancy test at screening?
- •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:
Exclusion Criteria
- •Open Phase Exclusion Criteria:
- •Has the patient received any previous pelvic radiotherapy (includes external beam and/or brachytherapy)?
- •Has the patient ever received apaziquone?
- •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?
- •Has the patient had any prior intravesical chemotherapy, exclusive of single-dose adjuvant intravesical chemotherapy immediately post-TURBT?
- •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)?
- •Does the patient have or has the patient had any bladder tumor with histology other than transitional cell carcinoma?
- •Does the patient have or has the patient had micro-papillary transitional cell carcinoma?
- •If the patient has recurrent papillary disease of the bladder, has the pathology been anything other than pTa in the past?
- •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?
Arms & Interventions
Apaziquone
Intervention: Apaziquone
Placebo
Placebo
Intervention: Placebo
Outcomes
Primary Outcomes
Time to Recurrence
Time Frame: Recurrence of cancer in the bladder during 24 months of follow-up
Time to recurrence is the time from randomization to the date of first histologically confirmed recurrence of bladder cancer (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 Outcomes
- Participants With Treatment Emergent Adverse Events (TEAEs)(24 Months from Randomization)
- Recurrence Rate at 24 Months(24 months)