Study to Improve Detection and Early Recurrence Rate in Bladder Cancer Patients Using Hexvix Fluorescence Cystoscopy

A Randomized, Comparative, Controlled Phase III, Multicenter Study of Hexvix Fluorescence Cystoscopy and White Light Cystoscopy in the Detection Of Papillary Bladder Cancer and the Early Recurrence Rate in Patients With Bladder Cancer

The purpose of this study is to document the additional detection of papillary bladder cancer and the reduced early recurrence due to the improved detection and resection of these tumors after Hexvix cystoscopy compared to standard cystoscopy in patients with papillary bladder cancer.

Study Overview

• Status: Completed
• Conditions: Bladder Cancer
• Intervention / Treatment: Procedure: Standard white light cystoscopy; Drug: Hexvix

Detailed Description

In superficial bladder cancer macroscopic tumors including non-invasive papillary tumors (Ta) in the bladder are relatively easy to visualize by cystoscopic examination under white light. However, dysplasia, carcinoma in situ (CIS) or small exophytic tumors are easily overlooked. These lesions are predictive of recurrence and progression of disease, and the identification of these lesions is a crucial factor for the prognosis of the patient. The present situation with 50-75% recurrence rate show the inadequacy of white light cystoscopy for detection and resection of the lesions.

A better detection of papillary bladder cancer and early detection of CIS lesions will provide the patient with a more complete TURB, a more optimal pharmacological treatment when needed, may reduce the need for follow up cystoscopies and hopefully result in a better prognosis for the patient.

The aim of the present study is to compare Hexvix cystoscopy with white light cystoscopy in the detection of histology confirmed papillary bladder cancer in patients with papillary bladder cancer and to compare early recurrence rate after Hexvix and white light transurethral resection (TURB) with white light TURB in patients with superficial bladder cancer.

• Study Type: Interventional
• Enrollment (Actual): 789
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Wien, Austria, 1090
    • AKH, Klinik für Urologie der Universität Wien
• Canada
  • Quebec, Canada, G1R 2J6
    • CHUQ Hotel-Dieu de Quebec
  • Ontario
    • Kingston, Ontario, Canada, K7L 2V7
      • Kingston General Hospital
• Germany
  • Giessen, Germany, 35392
    • University Clinic of Giessen, Department of Urology
  • München, Germany, 81377
    • Klinikum der Universität München-Großhardern, Urologische Klinik und Poliklinik
  • Planegg, Germany, 82152
    • Urologische Klinik München-Planegg
  • Regensburg, Germany, 93053
    • Akadem. Lehrkrankenhaus der Uni Regensburg, Klinik für Urologie
  • Tuebingen, Germany, 72076
    • Universitätsklinik Tuebingen, Universitätsklinik für Urologie
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Department of Urology, Academic Medical Center, University of Amsterdam
  • Nijmegen, Netherlands, 6500 HB
    • Department of Urology, UMC St. Radboud
• United States
  • California
    • Stanford, California, United States, 94305-5820
      • Stanford Cancer Center, Department of Urology
  • Florida
    • Gainesville, Florida, United States, 32608
      • V.A. Medical Center
    • Miami, Florida, United States, 33136
      • University of Miami School of Medicine
    • Pembroke Pines, Florida, United States, 33028
      • South Florida Clinical Research Center, Inc.
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • The Emory Clinic, Dept of Urology
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston University School of Medicine
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • St. Joseph Mercy Hospital- Ann Arbor
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Urologic Clinical Research Unit, Gonda 7102, Mayo Clinic Rochester
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • New York
    • New York, New York, United States, 10029-6574
      • Mount Sinai Medical Center, Department of Urology
    • Rochester, New York, United States, 14642
      • URMC
  • Ohio
    • Beachwood, Ohio, United States, 44120
      • Urological Institute at Beachwood Cleveland Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson Medical College, Department of Neurology
  • Tennessee
    • Nashville, Tennessee, United States, 37232-2765
      • Vanderbilt University Medical Center, Department of Urologic Surgery
  • Texas
    • Houston, Texas, United States, 77030-2726
      • Baylor College of Medicine, Scott Department of Urology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

The patients should be indicated for a cystoscopic examination for suspected or verified papillary bladder cancer and fulfill one or more of the following criteria:

• Patients with more than one initial bladder tumor confirmed on an outpatient cystoscopy.
• Patients having recurrence within 12 months confirmed on an outpatient cystoscopy
• Patients with more than one papillary lesion at recurrence independently of the time of the recurrence confirmed on an outpatient cystoscopy

Exclusion Criteria:

• Patients with known tumors in the prostatic urethra or distal urethra
• Gross hematuria. (Note: Gross hematuria is defined as a heavy bladder bleed resulting in marked amounts of blood in the urine, which may interfere with fluorescence cystoscopy. Where the bleed is light, the patient should not be excluded if in the investigator's opinion, rinsing during cystoscopy will alleviate the possible interference with fluorescence cystoscopy).
• Patient with porphyria.
• Known allergy to hexyl aminolevulinate hydrochloride or a similar compound.
• Participation in other clinical studies with investigational drugs either concurrently or within the last 30 days.
• Pregnant or breast-feeding (all women of child-bearing potential must document a negative serum or urine pregnancy test at screening and use the contraceptive pill or intrauterine device (IUD) during the treatments and for at least one month thereafter).
• Patients who have received BCG or chemotherapy within three months prior to the initial cystoscopy/TURB, except for a single dose of chemotherapy for prevention of seeding after resection.
• Conditions associated with a risk of poor protocol compliance.

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard White Light Cystoscopy	Procedure: Standard white light cystoscopy
Experimental: Standard White Light and Hexvix Fluorescence Cystoscopy	Procedure: Standard white light cystoscopy; Drug: Hexvix; Single Instillation, Transurethral Resection of the Bladder

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of Patients With >= 1 Ta or T1 Tumor Detected With Blue Light and Not White Light	Day 0
Comparison of the Proportions of Patients in the White Light Cystoscopy and Hexvix Groups Who Underwent TURB for a Histologically-confirmed Ta or T1 Tumor Who Had a Recurrence ( CIS, Ta, T1 or T2-T4 Tumor) Within 9 Months.	9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of False Positive Lesions of Hexvix Cystoscopy and White Light Cystoscopy.	The false detection rate for Hexvix cystoscopy was calculated as the total number of false positive lesions (i.e. lesions that were suspected with blue light but had negative histology according to the Standard of Truth central panel read) divided by the total number of lesions that were suspected with blue light (i.e., false positive divided by false positive plus true positive). The corresponding false detection rates were also calculated for white light cystoscopy for the two groups separately.	Day 0
Proportion of Patients With at Least One CIS Lesion Detected With Blue Light and None Seen With White Light.		Day 0

Collaborators and Investigators

• Sponsor: Photocure
• Investigators: Principal Investigator: H Barton Grossman, The University of Texas, MD Anderson Cancer Center, Department of Urology

Publications and helpful links

General Publications

• Stenzl A, Burger M, Fradet Y, Mynderse LA, Soloway MS, Witjes JA, Kriegmair M, Karl A, Shen Y, Grossman HB. Hexaminolevulinate guided fluorescence cystoscopy reduces recurrence in patients with nonmuscle invasive bladder cancer. J Urol. 2010 Nov;184(5):1907-13. doi: 10.1016/j.juro.2010.06.148. Epub 2010 Sep 17.

Study record dates

Study Major Dates

• Study Start: January 1, 2005
• Primary Completion (Actual): July 1, 2008
• Study Completion (Actual): August 1, 2008

Study Registration Dates

• First Submitted: October 4, 2005
• First Submitted That Met QC Criteria: October 4, 2005
• First Posted (Estimate): October 5, 2005

Study Record Updates

• Last Update Posted (Estimate): October 11, 2013
• Last Update Submitted That Met QC Criteria: August 5, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Keywords: Cystoscopy; Bladder Cancer; Fluorescence; Hexvix
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Disease Attributes; Recurrence; Urinary Bladder Neoplasms
• Other Study ID Numbers: PC B305/02