Bladder Cancer
Conditions
Keywords
Bladder Cancer, Hexvix, Fluorescence, Cystoscopy
Brief summary
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.
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.
Interventions
DRUGHexvix
Single Instillation, Transurethral Resection of the Bladder
PROCEDUREStandard white light cystoscopy
Sponsors
Photocure
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| 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
| Measure | Time frame | Description |
|---|---|---|
| Proportion of False Positive Lesions of Hexvix Cystoscopy and White Light Cystoscopy. | Day 0 | 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. |
| Proportion of Patients With at Least One CIS Lesion Detected With Blue Light and None Seen With White Light. | Day 0 | — |
Countries
Austria, Canada, Germany, Netherlands, United States
Participant flow
Recruitment details
A total of 814 patients were included in the study at 28 medical centers in the USA, Canada and Europe between January 2005 and September 2007.
Participants by arm
| Arm | Count |
|---|---|
| Comparator Standard White Light Cystoscopy | 361 |
| Hexvix Fluorescence Cystoscopy Standard White Light and Hexvix Fluorescence Cystoscopy | 365 |
| Total | 726 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to follow up etc | 3 | 21 |
| Overall Study | No pathology data | 12 | 9 |
| Overall Study | No Ta/T1 | 89 | 94 |
Baseline characteristics
| Characteristic | Comparator | Hexvix Fluorescence Cystoscopy | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 247 Participants | 243 Participants | 490 Participants |
| Age, Categorical Between 18 and 65 years | 114 Participants | 122 Participants | 236 Participants |
| Age Continuous | 69.6 years STANDARD_DEVIATION 10.63 | 68.5 years STANDARD_DEVIATION 10.68 | 69 years STANDARD_DEVIATION 10.7 |
| Sex: Female, Male Female | 77 Participants | 87 Participants | 164 Participants |
| Sex: Female, Male Male | 284 Participants | 278 Participants | 562 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 193 / 381 | 202 / 421 |
| serious Total, serious adverse events | 32 / 381 | 39 / 421 |
Outcome results
Primary
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.
Time frame: 9 months
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Hexvix Group | 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. | 47.2 percentage of participants |
| White Light Group | 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. | 56.1 percentage of participants |
Primary
Proportion of Patients With >= 1 Ta or T1 Tumor Detected With Blue Light and Not White Light
Time frame: Day 0
Population: Analysis was based on ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Hexvix Group | Proportion of Patients With >= 1 Ta or T1 Tumor Detected With Blue Light and Not White Light | 16.4 percentage of participants |
Secondary
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.
Time frame: Day 0
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Hexvix Group | Proportion of False Positive Lesions of Hexvix Cystoscopy and White Light Cystoscopy. | 12 Percetange of lesion |
| White Light Group | Proportion of False Positive Lesions of Hexvix Cystoscopy and White Light Cystoscopy. | 10 Percetange of lesion |
Secondary
Proportion of Patients With at Least One CIS Lesion Detected With Blue Light and None Seen With White Light.
Time frame: Day 0
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Hexvix Group | Proportion of Patients With at Least One CIS Lesion Detected With Blue Light and None Seen With White Light. | 31.7 percentage of participants |