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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Allergan
Information provided by (Responsible Party):
Spectrum Pharmaceuticals, Inc
ClinicalTrials.gov Identifier:
NCT01410565
First received: August 1, 2011
Last updated: August 9, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
Bladder Cancer
Drug: Apaziquone
Drug: Placebo
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Spectrum Pharmaceuticals, Inc:

Primary Outcome Measures:
  • Time to Recurrence [ Time Frame: Recurrence of cancer in the bladder during 24 months of follow-up ] [ Designated as safety issue: No ]
    Time to recurrence (from randomization) 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:
  • Recurrence rate at 24 Months [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Recurrence Rate at 12 Months [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
  • Time to Progression [ Time Frame: 24 Months after Randomization ] [ Designated as safety issue: No ]
  • Safety and Tolerability [ Time Frame: 24 Months from Randomization ] [ Designated as safety issue: Yes ]
    Safety and Tolerability will be mainly characterized by the number and severity of treatment emergent adverse events and treatment related AEs that occur or worsen after the first dose of study treatment.


Estimated Enrollment: 658
Study Start Date: July 2011
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Apaziquone Drug: Apaziquone
Apaziquone 4 mg in 40 mL diluent
Other Names:
  • EO9
  • EOquin
Placebo Comparator: Placebo
Placebo
Drug: Placebo
Placebo for Double Blind Phase

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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?
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01410565

  Hide Study Locations
Locations
United States, Arizona
Valley Urologic Associates
Glendale, Arizona, United States, 85308
Precision Trials, LLC
Phoenix, Arizona, United States, 85032
United States, California
South Orange County Medical Research Center
Laguna Woods, California, United States, 92653
United States, Colorado
The Urology Center of Colorado
Denver, Colorado, United States, 80211
United States, Connecticut
Connecticut Clinical Research Center
Middlebury, Connecticut, United States, 06762
United States, Georgia
Urology Enterprises
Marietta, Georgia, United States, 30060
United States, Idaho
North Idaho Urology
Coeur d'Alene, Idaho, United States, 83814
Idaho Urologic Institute, P.A.
Meridian, Idaho, United States, 83642
United States, Indiana
Northeast Indiana Research, LLC
Ft. Wayne, Indiana, United States, 46825
First Urology, PSC
Jeffersonville, Indiana, United States, 47130
United States, Louisiana
Regional Urology, LLC
Shreveport, Louisiana, United States, 71106
United States, Maryland
Anne Arundel Urology
Annapolis, Maryland, United States, 21401
United States, Michigan
Spectrum Health Medical Group
Grand Rapids, Michigan, United States, 49546
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55418
United States, Montana
Five Valleys Urology
Missoula, Montana, United States, 59802
United States, New Jersey
Delaware Valley Urology, LLC - Voorhees
Voorhees, New Jersey, United States, 08043
Delaware Valley Urology, LLC-Westampton
Westampton, New Jersey, United States, 08060
United States, New York
University Urology Associates
New York, New York, United States, 10016
Urology Associates of Rochester, LLC
Rochester, New York, United States, 14618
United States, Ohio
TriState Urologic Services PSC, Inc.
Cincinnati, Ohio, United States, 45212
United States, Pennsylvania
Urologic Consultants of Southeastern Pennsylvania, LLP
Bala Cynwyd, Pennsylvania, United States, 19004
Urology Health Specialists
Bryn Mawr, Pennsylvania, United States, 19010
Urological Associates of Lancaster
Lancaster, Pennsylvania, United States, 17604
United States, South Carolina
Carolina Urologic Research Center
Myrtle Beach, South Carolina, United States, 29572
United States, Texas
Urology Associates of South Texas
McAllen, Texas, United States, 78503
United States, Virginia
Urology of Virginia, PLLC
Virginia Beach, Virginia, United States, 23462
Urology of Virginia, PC
Virginia Beach, Virginia, United States, 23454
United States, Washington
Integrity Medical Research, LLC
Mountlake Terrace, Washington, United States, 98043
Canada, British Columbia
G. Steinhoff Clinical Research Pacific Urologic Research
Victoria, British Columbia, Canada, V8V3N1
Canada, Nova Scotia
Queen Elizabeth II Health Science Center
Halifax, Nova Scotia, Canada, B3H 1V7
Canada, Ontario
The Male/Female Health and Research Centre - Royal Court Medical Centre
Barrie, Ontario, Canada, L4M7G1
Brantford Urology Research
Brantford, Ontario, Canada, N3R4N3
G. Kenneth Jansz Medicine Professional Corporation
Burlington, Ontario, Canada, L7N3V2
Urology Resource Centre
Burlington, Ontario, Canada, L7S1V2
Kingston General Hospital / Queen's University
Kingston, Ontario, Canada, K7L3J7
Urology Associates, Urologic Medical Research
Kitchener, Ontario, Canada, N2N2B9
Mor Urology, Inc.
Newmarket, Ontario, Canada, L3X1W1
Office of Bernard Goldfarb
North Bay, Ontario, Canada, P1B7K8
Stanley Flax Medical Professional Corporation
North York, Ontario, Canada, M2J1V1
The Fe/Male Health Centre
Oakville, Ontario, Canada, L6H3P1
Urotec
Oshawa, Ontario, Canada, L1H7K4
Urology/Male Infertility
Scarborough, Ontario, Canada, M1S4V5
University Health Network Princess Margaret Hospital
Toronto, Ontario, Canada, M5G2M9
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada, M4N3M5
Canada, Quebec
Centre universitaire de sante McGill
Montreal, Quebec, Canada, H3G1A4
Centre Hospitalier Universitaire de Sherbrooke
Sherbrooke, Quebec, Canada, J1H5N4
Canada
Centre Hospitalier Universitaire de Quebec
Quebec, Canada, G1R3S3
Sponsors and Collaborators
Spectrum Pharmaceuticals, Inc
Allergan
Investigators
Study Director: Show-Li Sun, MD Spectrum Pharmaceuticals, Inc
  More Information

Publications:
Responsible Party: Spectrum Pharmaceuticals, Inc
ClinicalTrials.gov Identifier: NCT01410565     History of Changes
Other Study ID Numbers: SPI-1011
Study First Received: August 1, 2011
Last Updated: August 9, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Spectrum Pharmaceuticals, Inc:
Bladder Cancer
Non-Muscle Invasive Bladder Cancer
NMIBC
Apaziquone
EOquin
GU Cancer
TURBT

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Apaziquone
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 26, 2014