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

NCT01410565 | Terminated Phase 3 Results

• 1 other identifier: SPI-1011
• Study Type: interventional
• Target: 66
• Locations: 2 countries
• Sites: 47

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

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (2)

• Recurrence Rate at 24 Months

  24 months

• Participants With Treatment Emergent Adverse Events (TEAEs)

  24 Months from Randomization

Study Arms (2)

Apaziquone

ACTIVE COMPARATOR

Drug: Apaziquone

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Apaziquone DRUG

Apaziquone 4 mg in 40 mL diluent

Also known as: EO9, EOquin

Apaziquone

Placebo DRUG

Placebo for Double Blind Phase

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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?
• 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?
• Is patient's urethra (including prostatic urethra in men) endoscopically free of any visible TCC?
• 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?

You may not qualify if:

• 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?
• Does the patient have a bleeding disorder or a screening platelet count \< 50 x 109/L?
• Does the patient have a screening hemoglobin \< 10 mg/dL?
• Does the male patient have a serum PSA \> 10 ng/mL?
• Does the patient have a history of Acquired Immunodeficiency Syndrome or HIV positive?
• 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?

Sponsors & Collaborators

• Spectrum Pharmaceuticals, Inc: lead
• Allergan: collaborator

Study Sites (47)

Valley Urologic Associates

Glendale, Arizona, 85308, United States

Location

Precision Trials, LLC

Phoenix, Arizona, 85032, United States

Location

South Orange County Medical Research Center

Laguna Woods, California, 92653, United States

Location

The Urology Center of Colorado

Denver, Colorado, 80211, United States

Location

Connecticut Clinical Research Center

Middlebury, Connecticut, 06762, United States

Location

Urology Enterprises

Marietta, Georgia, 30060, United States

Location

North Idaho Urology

Coeur d'Alene, Idaho, 83814, United States

Location

Idaho Urologic Institute, P.A.

Meridian, Idaho, 83642, United States

Location

Northeast Indiana Research, LLC

Fort Wayne, Indiana, 46825, United States

Location

First Urology, PSC

Jeffersonville, Indiana, 47130, United States

Location

Regional Urology, LLC

Shreveport, Louisiana, 71106, United States

Location

Anne Arundel Urology

Annapolis, Maryland, 21401, United States

Location

Spectrum Health Medical Group

Grand Rapids, Michigan, 49546, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55418, United States

Location

Five Valleys Urology

Missoula, Montana, 59802, United States

Location

Delaware Valley Urology, LLC - Voorhees

Voorhees Township, New Jersey, 08043, United States

Location

Delaware Valley Urology, LLC-Westampton

Woodlane, New Jersey, 08060, United States

Location

University Urology Associates

New York, New York, 10016, United States

Location

Urology Associates of Rochester, LLC

Rochester, New York, 14618, United States

Location

TriState Urologic Services PSC, Inc.

Cincinnati, Ohio, 45212, United States

Location

Urologic Consultants of Southeastern Pennsylvania, LLP

Bala-Cynwyd, Pennsylvania, 19004, United States

Location

Urology Health Specialists

Bryn Mawr, Pennsylvania, 19010, United States

Location

Urological Associates of Lancaster

Lancaster, Pennsylvania, 17604, United States

Location

Carolina Urologic Research Center

Myrtle Beach, South Carolina, 29572, United States

Location

Urology Associates of South Texas

McAllen, Texas, 78503, United States

Location

Urology of Virginia, PC

Virginia Beach, Virginia, 23454, United States

Location

Urology of Virginia, PLLC

Virginia Beach, Virginia, 23462, United States

Location

Integrity Medical Research, LLC

Mountlake Terrace, Washington, 98043, United States

Location

G. Steinhoff Clinical Research Pacific Urologic Research

Victoria, British Columbia, V8V3N1, Canada

Location

Queen Elizabeth II Health Science Center

Halifax, Nova Scotia, B3H 1V7, Canada

Location

The Male/Female Health and Research Centre - Royal Court Medical Centre

Barrie, Ontario, L4M7G1, Canada

Location

Brantford Urology Research

Brantford, Ontario, N3R4N3, Canada

Location

G. Kenneth Jansz Medicine Professional Corporation

Burlington, Ontario, L7N3V2, Canada

Location

Urology Resource Centre

Burlington, Ontario, L7S1V2, Canada

Location

Kingston General Hospital / Queen's University

Kingston, Ontario, K7L3J7, Canada

Location

Urology Associates, Urologic Medical Research

Kitchener, Ontario, N2N2B9, Canada

Location

Mor Urology, Inc.

Newmarket, Ontario, L3X1W1, Canada

Location

Office of Bernard Goldfarb

North Bay, Ontario, P1B7K8, Canada

Location

Stanley Flax Medical Professional Corporation

North York, Ontario, M2J1V1, Canada

Location

The Fe/Male Health Centre

Oakville, Ontario, L6H3P1, Canada

Location

Urotec

Oshawa, Ontario, L1H7K4, Canada

Location

Urology/Male Infertility

Scarborough Village, Ontario, M1S4V5, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N3M5, Canada

Location

University Health Network Princess Margaret Hospital

Toronto, Ontario, M5G2M9, Canada

Location

Centre universitaire de sante McGill

Montreal, Quebec, H3G1A4, Canada

Location

Centre Hospitalier Universitaire de Quebec

Québec, Quebec, G1R3S3, Canada

Location

Centre Hospitalier Universitaire de Sherbrooke

Sherbrooke, Quebec, J1H5N4, Canada

Location

Related 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. Epub 2008 May 15.

  PMID: 18485394 BACKGROUND

• 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.

  PMID: 8196081 BACKGROUND

• 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.

  PMID: 18670272 BACKGROUND

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Non-Muscle Invasive Bladder Neoplasms

Interventions

apaziquone

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Results Point of Contact

• Title: Gajanan Bhat
• Organization: Spectrum Pharmaceutical Inc.

gajanan.bhat@sppirx.com

949-743-9219

Study Officials

• Show-Li Sun, MD

  Spectrum Pharmaceuticals, Inc

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 1, 2011
• First Posted: August 5, 2011
• Study Start: July 1, 2011
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: December 13, 2016
• Results First Posted: December 13, 2016

Record last verified: 2016-12

Locations

US (28); CA (19)