A Study of Blue Light Flexible Cystoscopy With Cysview in the Detection of Bladder Cancer in the Surveillance Setting

• Sponsor: Photocure (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02560584
• Collaborator: KARL STORZ Endoscopy-America, Inc. (Industry)
• Enrollment: 304
• Locations: 17
• Arm: 1
• Actual Duration (Months): 18.1
• Patients Per Site: 17.9
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

The purpose of this study is to investigate if blue light cystoscopy with Cysview improves detection of tumors in patients with bladder cancer during surveillance cystoscopy, using the KARL STORZ D-Light C PDD Flexible Videoscope System. Another purpose is to investigate if Cysview and blue light is safe and effective when used repeatedly.

Condition or Disease	Intervention/Treatment	Phase
Bladder Cancer	Drug: Hexaminolevulinate hydrochloride; Device: KARL STORZ D-Light C PDD Flexible Videoscope System	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 304 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: This is a prospective, open, comparative, within-patient controlled Phase 3 multicenter study in patients with bladder cancer. There is a maximum of three study visits for an enrolled patient: Visit 1: Screening visit Visit 2: Surveillance cystoscopy in white light (WL) followed by blue light (BL) Visit 3: Operating room (OR) cystoscopy in WL followed by BL for patients with suspicion of recurrence after surveillance cystoscopy. Cystoscopy in WL followed by BL is performed in all patients after Cysview instillation. Only patients with suspicious lesions at Visit 2 continue to a second cystoscopy in WL followed by BL at Visit 3.This is a prospective, open, comparative, within-patient controlled Phase 3 multicenter study in patients with bladder cancer. There is a maximum of three study visits for an enrolled patient:Visit 1: Screening visit Visit 2: Surveillance cystoscopy in white light (WL) followed by blue light (BL) Visit 3: Operating room (OR) cystoscopy in WL followed by BL for patients with suspicion of recurrence after surveillance cystoscopy. Cystoscopy in WL followed by BL is performed in all patients after Cysview instillation. Only patients with suspicious lesions at Visit 2 continue to a second cystoscopy in WL followed by BL at Visit 3.
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: A Prospective, Open, Comparative, Within Patient Controlled Multicenter Phase 3 Study of Blue Light Cystoscopy With Cysview and White Light Cystoscopy Using KARL STORZ D-Light C PDD Flexible Videoscope System in Detection of Bladder Cancer in Patients With Bladder Cancer
• Actual Study Start Date: Oct 1, 2015
• Actual Primary Completion Date: Apr 5, 2017
• Actual Study Completion Date: Apr 5, 2017

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Cysview arm In this single-arm trial, Cystoscopy in white light followed by blue light (BL) is performed in all applicable patients during 2 study visits; Visit 2 (Surveillance) and Visit 3 (Operating room procedure) All patients receive instillation of 100 mg hexaminolevulinate hydrochloride as intravesical solution (50 mL) in the bladder prior to cystoscopy. Retention time: 1-3 hours. Surveillance cystoscopy is performed with the investigational device KARL STORZ D-Light C PDD Flexible Videoscope System

Drug: Hexaminolevulinate hydrochloride; Instillation in bladder; Other Names: Cysview ; Device: KARL STORZ D-Light C PDD Flexible Videoscope System; Cystoscopy procedure

Outcome Measures

Primary Outcome Measures

1. Proportion of Patients With Histologically Confirmed Malignancy Where Malignancy is Only Detected With Blue Light Cystoscopy With Cysview and Not White Light Cystoscopy [At time of cystoscopy procedure]

   In the subsection of patients with histologically confirmed malignancy, the proportion of patients detected only by the use of blue light cystoscopy with Cysview is measured.

Secondary Outcome Measures

1. Proportion of Patients With Adverse Events Considered Causally Related to Cysview and/or Blue Light in the Surveillance Examination Compared With the OR Examination [At time of cystoscopy procedure]

2. Proportion of Patients With One or More Carcinoma in Situ (CIS) Lesions Detected With Blue Light Cystoscopy With Cysview and None With White Light Cystoscopy [At time of cystoscopy procedure]

   In the subsection of patients with histologically confirmed CIS, the proportion of patients detected only by blue light cystoscopy with Cysview is measured.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

1. Patients with bladder cancer in follow-up for tumor recurrence (Note: Patients must be included only at the first surveillance cystoscopy after a histologically confirmed tumor. The histologically confirmed tumor could either be from a TURB or from a surveillance cystoscopy where a biopsy was taken and a tumor was confirmed by histology)

2. History of one or more of the following:

• Multiple tumors

• Recurrent tumors

• High grade tumor(s)

Exclusion Criteria:

1. Gross haematuria. (Note: Gross haematuria is defined as a heavy bladder bleed resulting in significant amounts of blood in the urine, which may visually limit cystoscopy. Where the haematuria is light, the patient should not be excluded, if in the investigator's opinion, rinsing and/or electro-cautery during cystoscopy will alleviate the haematuria limitations to cystoscopy)

2. Patients who cannot undergo in-office or operating room cystoscopy (Note: Training patients are eligible even if they cannot undergo operating room cystoscopy)

3. Patients who have received Bacillus Calmette-Guérin (BCG) immunotherapy or intravesical chemotherapy within the past 6 weeks prior to the procedure

4. Porphyria

5. Known allergy to hexaminolevulinate hydrochloride or a similar compound

6. Pregnancy or breast-feeding (all women of child-bearing potential must document a negative urine pregnancy test before study inclusion and use adequate contraception during the study

7. Participation in other clinical studies with investigational drugs either concurrently or within the last 30 days

8. Patient is the investigator or any sub investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol

9. Patients that the investigator believes are unlikely to comply with the protocol, e.g. mental condition rendering the patient unable to understand the nature, scope, and possible consequences of participating in the clinical study, uncooperative attitude or unlikelihood of completing the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	USC Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
2	University of Chicago Medical Center	Chicago	Illinois	United States	60637
3	University of Iowa	Iowa City	Iowa	United States	52242
4	Johns Hopkins University	Baltimore	Maryland	United States	21205
5	University of Minnesota	Minneapolis	Minnesota	United States	55455
6	Montefiore Medical Center	Bronx	New York	United States	10461
7	NYU Langone Urology Associates	New York	New York	United States	10016
8	Columbia University Medical Center	New York	New York	United States	10032
9	University of North Carolina, Department of Urology	Chapel Hill	North Carolina	United States	27599
10	Ohio State University The James Cancer Hospital	Columbus	Ohio	United States	43210
11	University of Oklahoma-Stephenson Cancer Center	Oklahoma City	Oklahoma	United States	73104
12	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	10197
13	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
14	UT Southwestern Medical Center	Dallas	Texas	United States	75390
15	MD Anderson Cancer Center	Houston	Texas	United States	77030
16	Michael E. DeBakey VA Medical Center	Houston	Texas	United States	77030
17	University of Wisconsin	Madison	Wisconsin	United States	53792

Sponsors and Collaborators

• Photocure
• KARL STORZ Endoscopy-America, Inc.

Investigators

• Principal Investigator: Mark Schoenberg, MD, Montefiore Medical Center
• Principal Investigator: J. Stephen Jones, MD, The Cleveland Clinic

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 20, 2015

More Information

Publications

None provided.

• Responsible Party: Photocure
• ClinicalTrials.gov Identifier: NCT02560584
• Other Study ID Numbers: PC B308/13
• First Posted: Sep 25, 2015
• Last Update Posted: Jul 2, 2018
• Last Verified: May 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Photocure: Non-muscle invasive bladder cancer; NMIBC; Cysview
• Additional relevant MeSH terms: Urinary Bladder Neoplasms; Aminolevulinic Acid

Study Results

Participant Flow

Arm/Group Title	Cysview Arm
Arm/Group Description	In this single-arm trial, Cystoscopy in white light followed by blue light (BL) is performed in all applicable patients during 2 study visits; Visit 2 (Surveillance) and Visit 3 (Operating room procedure) All patients receive instillation of 100 mg hexaminolevulinate hydrochloride as intravesical solution (50 mL) in the bladder prior to cystoscopy. Retention time: 1-3 hours. Surveillance cystoscopy is performed with the investigational device KARL STORZ D-Light C PDD Flexible Videoscope System
Period Title: Overall Study
STARTED	304
COMPLETED	304
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Cysview Arm
Arm/Group Description	In this single-arm trial, Cystoscopy in white light followed by blue light (BL) is performed in all applicable patients during 2 study visits; Visit 2 (Surveillance) and Visit 3 (Operating room procedure) All patients receive instillation of 100 mg hexaminolevulinate hydrochloride as intravesical solution (50 mL) in the bladder prior to cystoscopy. Retention time: 1-3 hours. Surveillance cystoscopy is performed with the investigational device KARL STORZ D-Light C PDD Flexible Videoscope System
Overall Participants	304
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	69.0 (10.4)
Sex: Female, Male (Count of Participants)
Female	62 20.4%
Male	242 79.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	6 2%
Not Hispanic or Latino	296 97.4%
Unknown or Not Reported	2 0.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	10 3.3%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	20 6.6%
White	272 89.5%
More than one race	0 0%
Unknown or Not Reported	2 0.7%
Number of Previous Recurrences (number of previous recurrences) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [number of previous recurrences]	1.7 (2.0)
History of CIS (Count of Participants)
Count of Participants [Participants]	127 41.8%
History of High Grade (Grade 2 or 3) Ta or T1 (Count of Participants)
Count of Participants [Participants]	222 73%
Patients Treated with intravesical chemotherapy (Count of Participants)
Count of Participants [Participants]	114 37.5%
Patients with Previous Treatment with BCG Immunotherapy (Count of Participants)
Count of Participants [Participants]	251 82.6%

Outcome Measures

1. Primary Outcome

Title	Proportion of Patients With Histologically Confirmed Malignancy Where Malignancy is Only Detected With Blue Light Cystoscopy With Cysview and Not White Light Cystoscopy
Description	In the subsection of patients with histologically confirmed malignancy, the proportion of patients detected only by the use of blue light cystoscopy with Cysview is measured.
Time Frame	At time of cystoscopy procedure

Outcome Measure Data

Analysis Population Description

Patients with histologically confirmed malignancy

Arm/Group Title	Cysview Arm
Arm/Group Description	In this single-arm trial, Cystoscopy in white light followed by blue light (BL) is performed in all applicable patients during 2 study visits; Visit 2 (Surveillance) and Visit 3 (Operating room procedure) All patients receive instillation of 100 mg hexaminolevulinate hydrochloride as intravesical solution (50 mL) in the bladder prior to cystoscopy. Retention time: 1-3 hours. Surveillance cystoscopy is performed with the investigational device KARL STORZ D-Light C PDD Flexible Videoscope System
Measure Participants	63
Count of Participants [Participants]	13 4.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cysview Arm
	Comments	The proportion of patients with malignancy detected only with BLC with Cysview was to be analyzed using an exact one-sided test for a single proportion based on the cumulative binomial distribution with a significance level of 2.5%. Null hypothesis: Malignancy is detected with BL only in 0.5% or less of the patients
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Exact one-sided test for a single propor
	Comments

2. Secondary Outcome

Title	Proportion of Patients With Adverse Events Considered Causally Related to Cysview and/or Blue Light in the Surveillance Examination Compared With the OR Examination
Time Frame	At time of cystoscopy procedure

Outcome Measure Data

Analysis Population Description

This is a within patient control trial, where the white light (WL) cystoscopy was the comparator. Enrolled participants received a WL and blue light (BL) surveillance examination after Cysview instillation. Operating room (OR) cystoscopy in WL and BL was performed for patients with suspicion of recurrence after surveillance cystoscopy.

Arm/Group Title	Surveillance Examination	Surveillance + OR Examination
Arm/Group Description	Patients who received Cysview instillation in the surveillance examination.	Patients who received a Cysview instillation in both surveillance and OR examinations.
Measure Participants	304	103
Count of Participants [Participants]	6 2%	3 NaN

3. Secondary Outcome

Title	Proportion of Patients With One or More Carcinoma in Situ (CIS) Lesions Detected With Blue Light Cystoscopy With Cysview and None With White Light Cystoscopy
Description	In the subsection of patients with histologically confirmed CIS, the proportion of patients detected only by blue light cystoscopy with Cysview is measured.
Time Frame	At time of cystoscopy procedure

Outcome Measure Data

Analysis Population Description

Number of patients with histologically confirmed CIS

Arm/Group Title	Cysview Arm
Arm/Group Description	In this single-arm trial, Cystoscopy in white light followed by blue light (BL) is performed in all applicable patients during 2 study visits; Visit 2 (Surveillance) and Visit 3 (Operating room procedure) All patients receive instillation of 100 mg hexaminolevulinate hydrochloride as intravesical solution (50 mL) in the bladder prior to cystoscopy. Retention time: 1-3 hours. Surveillance cystoscopy is performed with the investigational device KARL STORZ D-Light C PDD Flexible Videoscope System
Measure Participants	26
Count of Participants [Participants]	9 3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cysview Arm
	Comments	The proportion of patients with one or more CIS lesions detected with BL and none with WL was to be evaluated using an exact binomial test for single proportion with a significance level of 2.5% (one-sided). Null hypothesis: One or more CIS lesions are detected with BLC with Cysview and none with WL in less than or equal to 0.1% of the patients.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Exact one-sided test for single proporti
	Comments

Adverse Events

Time Frame	The period of observation in the surveillance examination was defined as the period from instillation of Cysview until the patient left the hospital. The period of observation in the operating room examination was defined as the period from instillation of Cysview until hospital discharge or for a maximum of 24 hours after the instillation if the patient was still at the hospital.
Arm/Group Title	Cysview Arm
Arm/Group Description	In this single-arm trial, Cystoscopy in white light followed by blue light (BL) is performed in all applicable patients during 2 study visits; Visit 2 (Surveillance) and Visit 3 (Operating room procedure) All patients receive instillation of 100 mg hexaminolevulinate hydrochloride as intravesical solution (50 mL) in the bladder prior to cystoscopy. Retention time: 1-3 hours. Surveillance cystoscopy is performed with the investigational device KARL STORZ D-Light C PDD Flexible Videoscope System
All Cause Mortality
	Cysview Arm
	Affected / at Risk (%)	# Events
Total	0/304 (0%)
Serious Adverse Events
	Cysview Arm
	Affected / at Risk (%)	# Events
Total	1/304 (0.3%)
Respiratory, thoracic and mediastinal disorders
Aspiration, Pneumonia aspiration	1/304 (0.3%)	2
Other (Not Including Serious) Adverse Events
	Cysview Arm
	Affected / at Risk (%)	# Events
Total	17/304 (5.6%)
Gastrointestinal disorders
Nausea	1/304 (0.3%)	1
General disorders
Pain, Pyrexia	2/304 (0.7%)	2
Injury, poisoning and procedural complications
Procedural pain	2/304 (0.7%)	2
Renal and urinary disorders
Bladder discomfort, Bladder pain, Bladder spasm, Dysuria, Urethral pain, Urinary bladder hemorrhage	12/304 (3.9%)	14
Skin and subcutaneous tissue disorders
Dermatitis contact, erythema, priuritus	2/304 (0.7%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.