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

Bladder Cancer Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01410565
• Other study ID #: SPI-1011
• Status: Terminated
• Phase: Phase 3
• First received: August 1, 2011
• Last updated: December 12, 2016
• Start date: July 2011
• Est. completion date: March 2014

Study information

• Verified date: December 2016
• Source: Spectrum Pharmaceuticals, Inc
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 66
• Est. completion date: March 2014
• Est. primary completion date: March 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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?

Study Design

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

Related Conditions & MeSH terms

• Bladder Cancer
• Urinary Bladder Neoplasms

Intervention

Drug:
• Apaziquone
Apaziquone 4 mg in 40 mL diluent
• Placebo
Placebo for Double Blind Phase

Locations

Country	Name	City	State
Canada	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	Queen Elizabeth II Health Science Center	Halifax	Nova Scotia
Canada	Kingston General Hospital / Queen's University	Kingston	Ontario
Canada	Urology Associates, Urologic Medical Research	Kitchener	Ontario
Canada	Centre universitaire de sante McGill	Montreal	Quebec
Canada	Mor Urology, Inc.	Newmarket	Ontario
Canada	Office of Bernard Goldfarb	North Bay	Ontario
Canada	Stanley Flax Medical Professional Corporation	North York	Ontario
Canada	The Fe/Male Health Centre	Oakville	Ontario
Canada	Urotec	Oshawa	Ontario
Canada	Centre Hospitalier Universitaire de Quebec	Quebec
Canada	Urology/Male Infertility	Scarborough	Ontario
Canada	Centre Hospitalier Universitaire de Sherbrooke	Sherbrooke	Quebec
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	University Health Network Princess Margaret Hospital	Toronto	Ontario
Canada	G. Steinhoff Clinical Research Pacific Urologic Research	Victoria	British Columbia
United States	Anne Arundel Urology	Annapolis	Maryland
United States	Urologic Consultants of Southeastern Pennsylvania, LLP	Bala Cynwyd	Pennsylvania
United States	Urology Health Specialists	Bryn Mawr	Pennsylvania
United States	TriState Urologic Services PSC, Inc.	Cincinnati	Ohio
United States	North Idaho Urology	Coeur d'Alene	Idaho
United States	The Urology Center of Colorado	Denver	Colorado
United States	Northeast Indiana Research, LLC	Ft. Wayne	Indiana
United States	Valley Urologic Associates	Glendale	Arizona
United States	Spectrum Health Medical Group	Grand Rapids	Michigan
United States	First Urology, PSC	Jeffersonville	Indiana
United States	South Orange County Medical Research Center	Laguna Woods	California
United States	Urological Associates of Lancaster	Lancaster	Pennsylvania
United States	Urology Enterprises	Marietta	Georgia
United States	Urology Associates of South Texas	McAllen	Texas
United States	Idaho Urologic Institute, P.A.	Meridian	Idaho
United States	Connecticut Clinical Research Center	Middlebury	Connecticut
United States	University of Minnesota	Minneapolis	Minnesota
United States	Five Valleys Urology	Missoula	Montana
United States	Integrity Medical Research, LLC	Mountlake Terrace	Washington
United States	Carolina Urologic Research Center	Myrtle Beach	South Carolina
United States	University Urology Associates	New York	New York
United States	Precision Trials, LLC	Phoenix	Arizona
United States	Urology Associates of Rochester, LLC	Rochester	New York
United States	Regional Urology, LLC	Shreveport	Louisiana
United States	Urology of Virginia, PC	Virginia Beach	Virginia
United States	Urology of Virginia, PLLC	Virginia Beach	Virginia
United States	Delaware Valley Urology, LLC - Voorhees	Voorhees	New Jersey
United States	Delaware Valley Urology, LLC-Westampton	Westampton	New Jersey

Sponsors (2)

Lead Sponsor	Collaborator
Spectrum Pharmaceuticals, Inc	Allergan

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (3)

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. — View 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. — View 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Recurrence	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).	Recurrence of cancer in the bladder during 24 months of follow-up	No
Secondary	Recurrence Rate at 24 Months	Measurement the number of participants with the recurrence at 24 months.	24 months	No
Secondary	Participants With Treatment Emergent Adverse Events (TEAEs)	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.	24 Months from Randomization	Yes