Clinical trial NCT01410565: Efficacy and Safety of Multi-Instillations of Apaziquone in Patients With Non-Muscle Invasive Bladder Cancer
Official title: 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Bladder Cancer
Keywords: Bladder Cancer
Non-Muscle Invasive Bladder Cancer
NMIBC
Apaziquone
EOquin
GU Cancer
TURBT
Lead sponsor: Spectrum Pharmaceuticals, Inc
Sponsor class: INDUSTRY
Collaborators: name: Allergan
First posted: 2011-08-05
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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?

Primary outcomes:
measure: Time to Recurrence
timeFrame: Recurrence of cancer in the bladder during 24 months of follow-up
Secondary outcomes:
measure: Recurrence Rate at 24 Months
timeFrame: 24 months
measure: Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: 24 Months from Randomization
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Valley Urologic Associates
state: Arizona
city: Phoenix
country: United States
facility: Precision Trials, LLC
state: Arizona
city: Laguna Woods
country: United States
facility: South Orange County Medical Research Center
state: California
city: Denver
country: United States
facility: The Urology Center of Colorado
state: Colorado
city: Middlebury
country: United States
facility: Connecticut Clinical Research Center
state: Connecticut
city: Marietta
country: United States
facility: Urology Enterprises
state: Georgia
city: Coeur d'Alene
country: United States
facility: North Idaho Urology
state: Idaho
city: Meridian
country: United States
facility: Idaho Urologic Institute, P.A.
state: Idaho
city: Ft. Wayne
country: United States
facility: Northeast Indiana Research, LLC
state: Indiana
city: Jeffersonville
country: United States
facility: First Urology, PSC
state: Indiana
city: Shreveport
country: United States
facility: Regional Urology, LLC
state: Louisiana
city: Annapolis
country: United States
facility: Anne Arundel Urology
state: Maryland
city: Grand Rapids
country: United States
facility: Spectrum Health Medical Group
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Missoula
country: United States
facility: Five Valleys Urology
state: Montana
city: Voorhees
country: United States
facility: Delaware Valley Urology, LLC - Voorhees
state: New Jersey
city: Westampton
country: United States
facility: Delaware Valley Urology, LLC-Westampton
state: New Jersey
city: New York
country: United States
facility: University Urology Associates
state: New York
city: Rochester
country: United States
facility: Urology Associates of Rochester, LLC
state: New York
city: Cincinnati
country: United States
facility: TriState Urologic Services PSC, Inc.
state: Ohio
city: Bala Cynwyd
country: United States
facility: Urologic Consultants of Southeastern Pennsylvania, LLP
state: Pennsylvania
city: Bryn Mawr
country: United States
facility: Urology Health Specialists
state: Pennsylvania
city: Lancaster
country: United States
facility: Urological Associates of Lancaster
state: Pennsylvania
city: Myrtle Beach
country: United States
facility: Carolina Urologic Research Center
state: South Carolina
city: McAllen
country: United States
facility: Urology Associates of South Texas
state: Texas
city: Virginia Beach
country: United States
facility: Urology of Virginia, PC
state: Virginia
city: Virginia Beach
country: United States
facility: Urology of Virginia, PLLC
state: Virginia
city: Mountlake Terrace
country: United States
facility: Integrity Medical Research, LLC
state: Washington
city: Victoria
country: Canada
facility: G. Steinhoff Clinical Research Pacific Urologic Research
state: British Columbia
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Science Center
state: Nova Scotia
city: Barrie
country: Canada
facility: The Male/Female Health and Research Centre - Royal Court Medical Centre
state: Ontario
city: Brantford
country: Canada
facility: Brantford Urology Research
state: Ontario
city: Burlington
country: Canada
facility: G. Kenneth Jansz Medicine Professional Corporation
state: Ontario
city: Burlington
country: Canada
facility: Urology Resource Centre
state: Ontario
city: Kingston
country: Canada
facility: Kingston General Hospital / Queen's University
state: Ontario
city: Kitchener
country: Canada
facility: Urology Associates, Urologic Medical Research
state: Ontario
city: Newmarket
country: Canada
facility: Mor Urology, Inc.
state: Ontario
city: North Bay
country: Canada
facility: Office of Bernard Goldfarb
state: Ontario
city: North York
country: Canada
facility: Stanley Flax Medical Professional Corporation
state: Ontario
city: Oakville
country: Canada
facility: The Fe/Male Health Centre
state: Ontario
city: Oshawa
country: Canada
facility: Urotec
state: Ontario
city: Scarborough
country: Canada
facility: Urology/Male Infertility
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: University Health Network Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: Centre universitaire de sante McGill
state: Quebec
city: Sherbrooke
country: Canada
facility: Centre Hospitalier Universitaire de Sherbrooke
state: Quebec
city: Quebec
country: Canada
facility: Centre Hospitalier Universitaire de Quebec
Study officials:
affiliation: Spectrum Pharmaceuticals, Inc
name: Show-Li Sun, MD
role: STUDY_DIRECTOR
References:
citation: Cai T, Nesi G, Tinacci G, Zini E, Mondaini N, Boddi V, Mazzoli S, Bartoletti R. Can early single dose instillation of epirubicin improve bacillus Calmette-Guerin efficacy in patients with nonmuscle invasive high risk bladder cancer? Results from a prospective, randomized, double-blind controlled study. J Urol. 2008 Jul;180(1):110-5. doi: 10.1016/j.juro.2008.03.038. Epub 2008 May 15.
citation: Schellens JH, Planting AS, van Acker BA, Loos WJ, de Boer-Dennert M, van der Burg ME, Koier I, Krediet RT, Stoter G, Verweij J. Phase I and pharmacologic study of the novel indoloquinone bioreductive alkylating cytotoxic drug E09. J Natl Cancer Inst. 1994 Jun 15;86(12):906-12. doi: 10.1093/jnci/86.12.906.
citation: Stenzl A, Hennenlotter J, Schilling D. Can we still afford bladder cancer? Curr Opin Urol. 2008 Sep;18(5):488-92. doi: 10.1097/MOU.0b013e32830b8925.