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

NCT ID: NCT01410565

Last Updated: 2016-12-13

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 66 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-07-31
• Study Completion Date: 2014-03-31

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.

Conditions

Bladder Cancer

Keywords

Bladder Cancer; Non-Muscle Invasive Bladder Cancer; NMIBC; Apaziquone; EOquin; GU Cancer; TURBT

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Apaziquone

Group Type: ACTIVE_COMPARATOR

Apaziquone

Intervention Type: DRUG

Apaziquone 4 mg in 40 mL diluent

Placebo

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo for Double Blind Phase

Interventions

Apaziquone

Apaziquone 4 mg in 40 mL diluent

Intervention Type: DRUG

Placebo

Placebo for Double Blind Phase

Intervention Type: DRUG

Other Intervention Names

EO9; EOquin

Eligibility Criteria

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?

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

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?

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Allergan

INDUSTRY

Sponsor Role: collaborator

Spectrum Pharmaceuticals, Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Show-Li Sun, MD

Role: STUDY_DIRECTOR

Spectrum Pharmaceuticals, Inc

Locations

Valley Urologic Associates

Glendale, Arizona, United States

Precision Trials, LLC

Phoenix, Arizona, United States

South Orange County Medical Research Center

Laguna Woods, California, United States

The Urology Center of Colorado

Denver, Colorado, United States

Connecticut Clinical Research Center

Middlebury, Connecticut, United States

Urology Enterprises

Marietta, Georgia, United States

North Idaho Urology

Coeur d'Alene, Idaho, United States

Idaho Urologic Institute, P.A.

Meridian, Idaho, United States

Northeast Indiana Research, LLC

Fort Wayne, Indiana, United States

First Urology, PSC

Jeffersonville, Indiana, United States

Regional Urology, LLC

Shreveport, Louisiana, United States

Anne Arundel Urology

Annapolis, Maryland, United States

Spectrum Health Medical Group

Grand Rapids, Michigan, United States

University of Minnesota

Minneapolis, Minnesota, United States

Five Valleys Urology

Missoula, Montana, United States

Delaware Valley Urology, LLC - Voorhees

Voorhees Township, New Jersey, United States

Delaware Valley Urology, LLC-Westampton

Woodlane, New Jersey, United States

University Urology Associates

New York, New York, United States

Urology Associates of Rochester, LLC

Rochester, New York, United States

TriState Urologic Services PSC, Inc.

Cincinnati, Ohio, United States

Urologic Consultants of Southeastern Pennsylvania, LLP

Bala-Cynwyd, Pennsylvania, United States

Urology Health Specialists

Bryn Mawr, Pennsylvania, United States

Urological Associates of Lancaster

Lancaster, Pennsylvania, United States

Carolina Urologic Research Center

Myrtle Beach, South Carolina, United States

Urology Associates of South Texas

McAllen, Texas, United States

Urology of Virginia, PC

Virginia Beach, Virginia, United States

Urology of Virginia, PLLC

Virginia Beach, Virginia, United States

Integrity Medical Research, LLC

Mountlake Terrace, Washington, United States

G. Steinhoff Clinical Research Pacific Urologic Research

Victoria, British Columbia, Canada

Queen Elizabeth II Health Science Center

Halifax, Nova Scotia, 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

Kingston General Hospital / Queen's University

Kingston, Ontario, Canada

Urology Associates, Urologic Medical Research

Kitchener, Ontario, 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

Urology/Male Infertility

Scarborough Village, Ontario, Canada

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

University Health Network Princess Margaret Hospital

Toronto, Ontario, Canada

Centre universitaire de sante McGill

Montreal, Quebec, Canada

Centre Hospitalier Universitaire de Quebec

Québec, Quebec, Canada

Centre Hospitalier Universitaire de Sherbrooke

Sherbrooke, Quebec, Canada

Countries

United States; Canada

References

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.

Reference Type: BACKGROUND

PMID: 18485394 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 8196081 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18670272 (View on PubMed)

Other Identifiers

SPI-1011

Identifier Type: -

Identifier Source: org_study_id