Efficacy and Safety of Multi-Instillations of Apaziquone in Patients With Non-Muscle Invasive Bladder Cancer
- Registration Number
- NCT01410565
- Lead Sponsor
- Spectrum Pharmaceuticals, Inc
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 66
Open Phase Inclusion Criteria:
-
Has the patient given written informed consent and is the patient willing and able to abide by the protocol?
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Is the patient 18 years old or above?
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If the patient is a female of childbearing potential, is she using an acceptable/effective method of contraception?
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Does the female patient of childbearing potential have a negative serum pregnancy test at screening?
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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
-
Is the patient able to retain bladder instillations for a minimum of 60 minutes?
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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?
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Is patient's urethra (including prostatic urethra in men) endoscopically free of any visible TCC?
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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?
-
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:
-
Was all visible tumor resected at the initial TURBT?
-
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
Open Phase Exclusion Criteria:
-
Has the patient received any previous pelvic radiotherapy (includes external beam and/or brachytherapy)?
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Has the patient ever received apaziquone?
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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?
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Has the patient had any prior intravesical chemotherapy, exclusive of single-dose adjuvant intravesical chemotherapy immediately post-TURBT?
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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)?
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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?
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If the patient has recurrent papillary disease of the bladder, has the pathology been anything other than pTa in the past?
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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?
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Does the patient have a bleeding disorder or a screening platelet count < 50 x 109/L?
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Does the patient have a screening hemoglobin < 10 mg/dL?
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Does the male patient have a serum PSA > 10 ng/mL?
-
Does the patient have a history of Acquired Immunodeficiency Syndrome or HIV positive?
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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?
-
Has the patient participated in an investigational protocol within the past 90 days?
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Is the patient pregnant or breast feeding?
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Does the patient have a life expectancy of <3 years?
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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?
-
Does the patient have documented vesicoureteral reflux or an indwelling ureteral stent?
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Does the patient have tumor in a bladder diverticulum?
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Does the patient have a known allergy to red color food dye?
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Placebo Apaziquone Apaziquone -
- Primary Outcome Measures
Name Time Method Time to Recurrence 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 Outcome Measures
Name Time Method Participants With Treatment Emergent Adverse Events (TEAEs) 24 Months from Randomization TEAEs will be mainly characterized by the number of treatment emergent adverse events and treatment related AEs that occur or worsen after the first dose of study treatment.
Recurrence Rate at 24 Months 24 months Measurement the number of participants with the recurrence at 24 months.
Trial Locations
- Locations (47)
G. Steinhoff Clinical Research Pacific Urologic Research
🇨🇦Victoria, British Columbia, Canada
Centre Hospitalier Universitaire de Sherbrooke
🇨🇦Sherbrooke, Quebec, Canada
Idaho Urologic Institute, P.A.
🇺🇸Meridian, Idaho, United States
Northeast Indiana Research, LLC
🇺🇸Ft. Wayne, Indiana, United States
University Urology Associates
🇺🇸New York, New York, United States
Kingston General Hospital / Queen's University
🇨🇦Kingston, Ontario, Canada
Valley Urologic Associates
🇺🇸Glendale, Arizona, United States
Urologic Consultants of Southeastern Pennsylvania, LLP
🇺🇸Bala Cynwyd, Pennsylvania, United States
Urology Enterprises
🇺🇸Marietta, Georgia, United States
Anne Arundel Urology
🇺🇸Annapolis, Maryland, United States
The Urology Center of Colorado
🇺🇸Denver, Colorado, United States
Urology Associates of Rochester, LLC
🇺🇸Rochester, New York, United States
Centre universitaire de sante McGill
🇨🇦Montreal, Quebec, Canada
Regional Urology, LLC
🇺🇸Shreveport, Louisiana, United States
Urology Health Specialists
🇺🇸Bryn Mawr, Pennsylvania, United States
Urological Associates of Lancaster
🇺🇸Lancaster, Pennsylvania, United States
South Orange County Medical Research Center
🇺🇸Laguna Woods, California, United States
TriState Urologic Services PSC, Inc.
🇺🇸Cincinnati, Ohio, United States
Urology Associates of South Texas
🇺🇸McAllen, Texas, United States
Integrity Medical Research, LLC
🇺🇸Mountlake Terrace, Washington, United States
Office of Bernard Goldfarb
🇨🇦North Bay, Ontario, Canada
Delaware Valley Urology, LLC - Voorhees
🇺🇸Voorhees, New Jersey, United States
Mor Urology, Inc.
🇨🇦Newmarket, Ontario, Canada
Urotec
🇨🇦Oshawa, Ontario, Canada
The Fe/Male Health Centre
🇨🇦Oakville, Ontario, Canada
First Urology, PSC
🇺🇸Jeffersonville, Indiana, United States
Spectrum Health Medical Group
🇺🇸Grand Rapids, Michigan, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Urology of Virginia, PC
🇺🇸Virginia Beach, Virginia, United States
The Male/Female Health and Research Centre - Royal Court Medical Centre
🇨🇦Barrie, Ontario, Canada
Brantford Urology Research
🇨🇦Brantford, Ontario, Canada
G. Kenneth Jansz Medicine Professional Corporation
🇨🇦Burlington, Ontario, Canada
Urology Resource Centre
🇨🇦Burlington, Ontario, Canada
Urology Associates, Urologic Medical Research
🇨🇦Kitchener, Ontario, Canada
Stanley Flax Medical Professional Corporation
🇨🇦North York, Ontario, Canada
Sunnybrook Health Sciences Centre
🇨🇦Toronto, Ontario, Canada
Centre Hospitalier Universitaire de Quebec
🇨🇦Quebec, Canada
Connecticut Clinical Research Center
🇺🇸Middlebury, Connecticut, United States
Queen Elizabeth II Health Science Center
🇨🇦Halifax, Nova Scotia, Canada
Five Valleys Urology
🇺🇸Missoula, Montana, United States
Delaware Valley Urology, LLC-Westampton
🇺🇸Westampton, New Jersey, United States
North Idaho Urology
🇺🇸Coeur d'Alene, Idaho, United States
Precision Trials, LLC
🇺🇸Phoenix, Arizona, United States
Carolina Urologic Research Center
🇺🇸Myrtle Beach, South Carolina, United States
Urology of Virginia, PLLC
🇺🇸Virginia Beach, Virginia, United States
University Health Network Princess Margaret Hospital
🇨🇦Toronto, Ontario, Canada
Urology/Male Infertility
🇨🇦Scarborough, Ontario, Canada