Instillation of Gemcitabine in Patients With Superficial Bladder Cancer

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00191477
• Collaborator: (none)
• Enrollment: 355
• Location: 1
• Arms: 2
• Duration (Months): 53
• Patients Per Site Per Month: 6.7

Study Details

Study Description

Brief Summary

A randomized, double-blind, placebo-controlled Phase 3 multicenter study to assess the efficacy and safety of intravesical instillation of gemcitabine versus placebo immediately after transurethral resection of the bladder tumor.

Condition or Disease	Intervention/Treatment	Phase
Bladder Neoplasms	Drug: Gemcitabine; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 355 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Multicenter Study of Immediate Postoperative Instillation of Gemcitabine in Patients With Superficial Transitional Cell Carcinoma of the Bladder
• Study Start Date: Jan 1, 2004
• Actual Primary Completion Date: Mar 1, 2008
• Actual Study Completion Date: Jun 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A	Drug: Gemcitabine; 2000 mg, intravesicular instillation x 1 immediately post transurethral resection of the bladder tumor (TUR-BT); Other Names: LY 188011 Gemzar
Placebo Comparator: B	Drug: Placebo; intravesicular instillation x 1 immediately post transurethral resection of the bladder tumor (TUR-BT)

Outcome Measures

Primary Outcome Measures

1. Recurrence-Free Survival (RFS) [Surgery to recurrence or death (Follow-up assessments were performed at 3 and 6 months after the first TUR-BT, and every 6 months thereafter, until recurrence/progression of disease, or until the end of study, up to 24 months)]

   Defined as the time from study enrollment to the date of the first procedure confirming histopathological recurrence or disease progression or death from any cause. Recurrence-free survival (RFS) was censored at the date of the last follow-up visit for participants who were still alive and who had no recurrence/progression.

Secondary Outcome Measures

1. Time to Recurrence [Surgery to recurrence (Follow-up assessments were performed at 3 and 6 months after the first TUR-BT, and every 6 months thereafter, until recurrence/progression of disease, or until the end of study, up to 24 months)]

   Time from enrollment to first confirmation of histopathological recurrence or disease progression. Time to recurrence was censored on date of death for patients who died, and on date of last visit for patients who were alive, without recurrence.

2. Recurrence-Free Survival (RFS) in Subgroups [Surgery to recurrence or death (Follow-up assessments were performed at 3 and 6 months after the first TUR-BT, and every 6 months thereafter, until recurrence/progression of disease, or until the end of study, up to 24 months)]

   Defined as the time from study enrollment to the date of the first procedure confirming histopathological recurrence or disease progression or death from any cause. Recurrence-free survival was censored at the date of the last follow-up visit for participants who were still alive and who had no recurrence/progression.

3. Tumor Recurrence Type [Surgery to recurrence (Follow-up assessments were performed at 3 and 6 months after the first TUR-BT, and every 6 months thereafter, until recurrence/progression of disease, or until the end of study, up to 24 months)]

   Tumor recurrence type (superficial, stage pTA or pT1; or muscle-invasive, stage≥pT2) was classified according to American Joint Committee on Cancer Staging Criteria for Bladder Cancer (AJCC Cancer Staging Manual, 6th edition).

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Clinical evidence of superficial transitional cell carcinoma of the bladder

• Males or females at least 18 years of age

• Karnofsky Performance Status greater than or equal to 70%

• Patient compliance and geographic proximity that allow adequate follow-up

• Female patients with reproductive potential must use a reliable contraceptive method if appropriate (for example, intrauterine device [IUD], birth control pills, or barrier device) during the study. Female patients with reproductive potential must have a negative serum pregnancy test within 7 days of study enrollment.

• Signed informed consent.

Exclusion Criteria:

• Clinical evidence of muscle-invasive or locally advanced bladder cancer

• Clinical evidence of upper urinary tract tumor

• Distant metastases

• Other malignancies within the last 2 years, except non-melanotic skin tumors, carcinoma in situ of the cervix or organ-confined prostate cancer after curative therapy

• Severe concomitant psychiatric disease

• Febrile, active infection

• Other serious concomitant disorders that would compromise the safety of the patient or his/her ability to complete the study according to the protocol, at the discretion of the investigator (for example, unstable angina pectoris, uncontrolled diabetes mellitus)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For additional information regarding investigative sites for this trial contact 1-877-CTLILLY (1-877-285-4559,1-317-615-4559) Mon-Fri from 9AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physici	Reinfeld		Germany	23858

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Chair: Call 1-877-CTLILLY(1-877-285-4559) or 1-317-615-4559 Mon-Fri 9AM - 5PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Lilly Clinical Trial Registry

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00191477
• Other Study ID Numbers: 6138; B9E-MC-S274
• First Posted: Sep 19, 2005
• Last Update Posted: Oct 28, 2009
• Last Verified: Sep 1, 2009

• Additional relevant MeSH terms: Urinary Bladder Neoplasms; Gemcitabine

Study Results

Participant Flow

Pre-assignment Detail	355 participants were enrolled and randomized (included here in disposition); however, due to study design, only 328 (N=166 Gemcitabine and N=162 Placebo) actually received study drug (Full Analysis Set).

Arm/Group Title	Gemcitabine	Placebo
Arm/Group Description	Gemcitabine: 2000 mg, intravesicular instillation x 1 immediately post transurethral resection of the bladder tumor (TUR-BT)	Placebo: intravesicular instillation x 1 immediately post transurethral resection of the bladder tumor (TUR-BT)
Period Title: Overall Study
STARTED	179	176
Received Study Drug	166	162
COMPLETED	41	47
NOT COMPLETED	138	129

Baseline Characteristics

Arm/Group Title	Gemcitabine	Placebo	Total
Arm/Group Description	Gemcitabine: 2000 mg, intravesicular instillation x 1 immediately post transurethral resection of the bladder tumor (TUR-BT)	Placebo: intravesicular instillation x 1 immediately post transurethral resection of the bladder tumor (TUR-BT)	Total of all reporting groups
Overall Participants	166	162	328
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.2 (11.9)	66.3 (11.0)	64.7 (11.5)
Sex: Female, Male (Count of Participants)
Female	39 23.5%	26 16%	65.0 19.8%
Male	127 76.5%	136 84%	263.0 80.2%
Region of Enrollment (participants) [Number]
Germany	131 78.9%	126 77.8%	257.0 78.4%
Turkey	35 21.1%	36 22.2%	71.0 21.6%
Karnofsky Performance Status (participants) [Number]
70 - Unable to carry on normal activity	1 0.6%	1 0.6%	2.0 0.6%
80 - Activity with effort; some signs of disease	13 7.8%	7 4.3%	20.0 6.1%
90 - Normal activity; minor signs of disease	33 19.9%	49 30.2%	82.0 25%
100 - Normal no complaints; no evidence of disease	118 71.1%	104 64.2%	222.0 67.7%
Unspecified	1 0.6%	1 0.6%	2.0 0.6%
Newly Diagnosed versus Recurrent Disease (participants) [Number]
Recurrent Disease	43 25.9%	40 24.7%	83.0 25.3%
Newly Diagnosed	123 74.1%	122 75.3%	245.0 74.7%
Race/Ethnicity (participants) [Number]
White	166 100%	162 100%	328 100%
Results of Initial Transurethral Resection of a Bladder Tumor (TUR-BT): Number of Visible Lesions (participants) [Number]
No Lesions (No Specific Sites Documented)	4 2.4%	5 3.1%	9.0 2.7%
1 Lesion	87 52.4%	96 59.3%	183.0 55.8%
2 Lesions	42 25.3%	27 16.7%	69.0 21%
3 Lesions	18 10.8%	14 8.6%	32.0 9.8%
4 Lesions	7 4.2%	10 6.2%	17.0 5.2%
>=5 Lesions	8 4.8%	10 6.2%	18.0 5.5%
Results of Transurethral Resection of Bladder Tumor (TUR-BT): Final Pathological Disease Stage (participants) [Number]
pTx: Primary Tumor Cannot be Assessed	3 1.8%	0 0%	3.0 0.9%
pT0: No Evidence of Primary Tumor	0 0%	0 0%	0.0 0%
pTa: Noninvasive Papillary Carcinoma	93 56%	88 54.3%	181.0 55.2%
pT1: Tumor Invades Subepithelial Connective Tissue	31 18.7%	36 22.2%	67.0 20.4%
>=pT2: Tumor Invades Wider Area	12 7.2%	10 6.2%	22.0 6.7%
Cis: Carcinoma in situ ("Flat Tumor")	5 3%	6 3.7%	11.0 3.4%
No Malignancy	21 12.7%	22 13.6%	43.0 13.1%
Unspecified	1 0.6%	0 0%	1.0 0.3%
Results of Transurethral Resection on a Bladder Tumor (TUR-BT): Final Disease Grade (participants) [Number]
G1 - Well Differentiated	59 35.5%	66 40.7%	125.0 38.1%
G2 - Moderately Differentiated	50 30.1%	48 29.6%	98.0 29.9%
G3 - Poorly Differentiated	25 15.1%	24 14.8%	49.0 14.9%
G4 - Undifferentiated	3 1.8%	1 0.6%	4.0 1.2%
GX - Unknown	8 4.8%	1 0.6%	9.0 2.7%
Unspecified	21 12.7%	22 13.6%	43.0 13.1%

Outcome Measures

1. Primary Outcome

Title	Recurrence-Free Survival (RFS)
Description	Defined as the time from study enrollment to the date of the first procedure confirming histopathological recurrence or disease progression or death from any cause. Recurrence-free survival (RFS) was censored at the date of the last follow-up visit for participants who were still alive and who had no recurrence/progression.
Time Frame	Surgery to recurrence or death (Follow-up assessments were performed at 3 and 6 months after the first TUR-BT, and every 6 months thereafter, until recurrence/progression of disease, or until the end of study, up to 24 months)

Outcome Measure Data

Analysis Population Description

This is the Full Analysis Set population and contains all randomized participants who received the single instillation of Gemcitabine or Placebo.

Arm/Group Title	Gemcitabine	Placebo
Arm/Group Description	Gemcitabine: 2000 mg, intravesicular instillation x 1 immediately post transurethral resection of the bladder tumor (TUR-BT)	Placebo: intravesicular instillation x 1 immediately post transurethral resection of the bladder tumor (TUR-BT)
Measure Participants	166	162
Median (Full Range) [Months]	37.2	40.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gemcitabine, Placebo
	Comments	Sample-size calculation based on estimated 1-year recurrence-free survival (RFS) rates of 63% (gemcitabine) and 50% (placebo). 191 critical events were required to detect a difference in RFS (80% power, log-rank test, alpha=0.050). Sample size of 328 patients with clinical evidence of superficial bladder cancer needed to observe these 191 events within a 24-month follow-up period, assuming 246 of these patients would receive instillation and have histopathological diagnosis of pTa/pT1(G1-3/Gx).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.777
	Comments	Only 87 recurrences and 7 deaths were documented at planned end of follow-up. The study was stopped early for futility reasons based on an interim analysis using pre-defined stopping boundaries for the hazard ratio (HR) of RFS.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.946
	Confidence Interval	() 95%; 0.643 to 1.392
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Post-Hoc Outcome

Title	Percentage of Participants Without Tumor Recurrence
Description	Because median time to recurrence was not reached, percentage of participants without event was estimated using Kaplan-Meier method. Time to recurrence was censored on date of death for patients who died, and on date of last visit for patients who were alive, without recurrence.
Time Frame	Surgery to recurrence (Follow-up assessments were performed at 3 and 6 months after the first TUR-BT, and every 6 months thereafter, until recurrence/progression of disease, or until the end of study, up to 24 months)

Outcome Measure Data

Analysis Population Description

Efficacy Eligible population contains the Full Analysis Set participants with histopathologically confirmed papillary superficial transitional cell carcinoma of the bladder.

Arm/Group Title	Gemcitabine	Placebo
Arm/Group Description	Gemcitabine: 2000 mg, intravesicular instillation x 1 immediately post transurethral resection of the bladder tumor (TUR-BT)	Placebo: intravesicular instillation x 1 immediately post transurethral resection of the bladder tumor (TUR-BT)
Measure Participants	124	124
Recurrence-Free at 12 Months	78.4 47.2%	76.9 47.5%
Recurrence-Free at 24 Months	66.3 39.9%	63.7 39.3%

3. Post-Hoc Outcome

Title	Percentage of Participants in Subgroups With Recurrence-Free Survival (RFS) at 12 and 24 Months
Description	RFS rate was estimated using Kaplan-Meier method. RFS was analyzed in different subgroups based on risk, disease status, and concomitant Bacillus Calmette-Guerin (BCG) instillations. Risk: Grading (G1,G2,G3) was performed according to American Joint Committee on Cancer Staging Criteria for Bladder Cancer. Newly diagnosed disease: Initial diagnosis at study entry. Recurrent disease: history of at least one superficial bladder tumor that was surgically treated and relapsed prior to study entry. With BCG: received at least one instillation of BCG during study. Without BCG: didn't receive BCG.
Time Frame	Surgery to recurrence or death (Follow-up assessments were performed at 3 and 6 months after the first TUR-BT, and every 6 months thereafter, until recurrence/progression of disease, or until the end of study, up to 24 months)

Outcome Measure Data

Analysis Population Description

Efficacy Eligible population consists of the Full Analysis Set (randomized) participants with histopathologically confirmed papillary superficial transitional cell carcinoma of the bladder.

Arm/Group Title	Gemcitabine	Placebo
Arm/Group Description	Gemcitabine: 2000 mg, intravesicular instillation x 1 immediately post transurethral resection of the bladder tumor (TUR-BT)	Placebo: intravesicular instillation x 1 immediately post transurethral resection of the bladder tumor (TUR-BT)
Measure Participants	124	124
Low Risk (G1/G2) - 12 Months (N=106, N=109)	78.5 47.3%	78.4 48.4%
Low Risk (G1/G2) - 24 Months (N=106, N=109)	63.9 38.5%	64.3 39.7%
High Risk (G3) - 12 Months (N=13, N=14)	66.7 40.2%	42.4 26.2%
High Risk (G3) - 24 Months (N=13, N=14)	57.1 34.4%	31.8 19.6%
Newly Diagnosed Disease - 12 Months (N=94, N=98)	79.3 47.8%	79.8 49.3%
Newly Diagnosed Disease - 24 Months (N=94, N=98)	65.4 39.4%	63.6 39.3%
Recurrent Disease - 12 Months (N=30, N=26)	72.2 43.5%	58.9 36.4%
Recurrent Disease - 24 Months (N=30, N=26)	59.5 35.8%	50.5 31.2%
With BCG - 12 Months (N=13, N=21)	61.5 37%	79.4 49%
With BCG - 24 Months (N=13, N=21)	49.2 29.6%	63.5 39.2%
Without BCG - 12 Months (N=111, N=103)	79.9 48.1%	74.5 46%
Without BCG - 24 Months (N=111, N=103)	65.8 39.6%	60.1 37.1%

4. Secondary Outcome

Title	Time to Recurrence
Description	Time from enrollment to first confirmation of histopathological recurrence or disease progression. Time to recurrence was censored on date of death for patients who died, and on date of last visit for patients who were alive, without recurrence.
Time Frame	Surgery to recurrence (Follow-up assessments were performed at 3 and 6 months after the first TUR-BT, and every 6 months thereafter, until recurrence/progression of disease, or until the end of study, up to 24 months)

Outcome Measure Data

Analysis Population Description

Because median time to recurrence was not reached in placebo arm, percentages of participants without recurrence are reported as post-hoc outcome measure (see #5. Post-hoc Outcome Measure). Efficacy Eligible population consists of randomized patients with histopathologically confirmed papillary superficial transitional cell carcinoma of bladder.

Arm/Group Title	Gemcitabine	Placebo
Arm/Group Description	Gemcitabine: 2000 mg, intravesicular instillation x 1 immediately post transurethral resection of the bladder tumor (TUR-BT)	Placebo: intravesicular instillation x 1 immediately post transurethral resection of the bladder tumor (TUR-BT)
Measure Participants	0	0

5. Secondary Outcome

Title	Recurrence-Free Survival (RFS) in Subgroups
Description	Defined as the time from study enrollment to the date of the first procedure confirming histopathological recurrence or disease progression or death from any cause. Recurrence-free survival was censored at the date of the last follow-up visit for participants who were still alive and who had no recurrence/progression.
Time Frame	Surgery to recurrence or death (Follow-up assessments were performed at 3 and 6 months after the first TUR-BT, and every 6 months thereafter, until recurrence/progression of disease, or until the end of study, up to 24 months)

Outcome Measure Data

Analysis Population Description

Because median time for RFS was not reached in all subgroups, patients (%) with RFS are reported as post-hoc outcome #6. There was no statistically significant difference between treatment arms in any subgroup. Population consists of randomized patients with histopathologically confirmed papillary superficial transitional cell carcinoma of bladder.

Arm/Group Title	Gemcitabine	Placebo
Arm/Group Description	Gemcitabine: 2000 mg, intravesicular instillation x 1 immediately post transurethral resection of the bladder tumor (TUR-BT)	Placebo: intravesicular instillation x 1 immediately post transurethral resection of the bladder tumor (TUR-BT)
Measure Participants	0	0

6. Secondary Outcome

Title	Tumor Recurrence Type
Description	Tumor recurrence type (superficial, stage pTA or pT1; or muscle-invasive, stage≥pT2) was classified according to American Joint Committee on Cancer Staging Criteria for Bladder Cancer (AJCC Cancer Staging Manual, 6th edition).
Time Frame	Surgery to recurrence (Follow-up assessments were performed at 3 and 6 months after the first TUR-BT, and every 6 months thereafter, until recurrence/progression of disease, or until the end of study, up to 24 months)

Outcome Measure Data

Analysis Population Description

Efficacy Eligible population consists of the Full Analysis Set participants with histopathologically confirmed papillary superficial transitional cell carcinoma of the bladder.

Arm/Group Title	Gemcitabine	Placebo
Arm/Group Description	Gemcitabine: 2000 mg, intravesicular instillation x 1 immediately post transurethral resection of the bladder tumor (TUR-BT)	Placebo: intravesicular instillation x 1 immediately post transurethral resection of the bladder tumor (TUR-BT)
Measure Participants	124	124
No Tumor Recurrence	76 45.8%	78 48.1%
Superficial Tumor - Stage pTa or pT1	44 26.5%	45 27.8%
Muscle-Invasive Tumor - Any Stage ≥pT2	3 1.8%	1 0.6%
pTx - Tumor Cannot be Assessed	1 0.6%	0 0%

Adverse Events

Arm/Group Title	Gemcitabine		Placebo
Arm/Group Description	Gemcitabine: 2000 mg, intravesicular instillation x 1 immediately post transurethral resection of bladder tumor (TUR-BT)		Placebo: intravesicular instillation x 1 immediately post transurethral resection of bladder tumor (TUR-BT)
All Cause Mortality
	Gemcitabine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Gemcitabine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/166 (10.2%)		10/162 (6.2%)
Cardiac disorders
Angina pectoris	1/166 (0.6%)	1	0/162 (0%)	0
Gastrointestinal disorders
Enterovesical fistula	1/166 (0.6%)	1	0/162 (0%)	0
Inguinal hernia	1/166 (0.6%)	1	0/162 (0%)	0
Infections and infestations
Pyelonephritis	1/166 (0.6%)	1	0/162 (0%)	0
Septic shock	0/166 (0%)	0	1/162 (0.6%)	1
Injury, poisoning and procedural complications
Post procedural haemorrhage	1/166 (0.6%)	1	0/162 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cervix carcinoma	1/166 (0.6%)	1	0/162 (0%)	0
Metastases to lymph nodes	0/166 (0%)	0	1/162 (0.6%)	1
Prostatic adenoma	1/166 (0.6%)	1	0/162 (0%)	0
Nervous system disorders
Ischaemic cerebral infarction	1/166 (0.6%)	1	0/162 (0%)	0
Renal and urinary disorders
Renal colic	0/166 (0%)	0	1/162 (0.6%)	1
Ureteric stenosis	1/166 (0.6%)	1	0/162 (0%)	0
Urinary bladder haemorrhage	0/166 (0%)	0	1/162 (0.6%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	1/166 (0.6%)	1	0/162 (0%)	0
Surgical and medical procedures
Cystoprostatectomy	1/166 (0.6%)	1	1/162 (0.6%)	1
Urinary bladder excision	8/166 (4.8%)	8	5/162 (3.1%)	5
Vascular disorders
Aortic aneurysm	1/166 (0.6%)	1	0/162 (0%)	0
Haemorrhage	1/166 (0.6%)	1	0/162 (0%)	0
Hypertension	1/166 (0.6%)	1	0/162 (0%)	0
Other (Not Including Serious) Adverse Events
	Gemcitabine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	38/166 (22.9%)		36/162 (22.2%)
Cardiac disorders
Arrhythmia	0/166 (0%)	0	1/162 (0.6%)	1
Atrial fibrillation	0/166 (0%)	0	1/162 (0.6%)	1
Bundle branch block right	0/166 (0%)	0	1/162 (0.6%)	1
Cardiopulmonary failure	1/166 (0.6%)	1	0/162 (0%)	0
Coronary artery disease	1/166 (0.6%)	1	0/162 (0%)	0
Tachycardia	0/166 (0%)	0	1/162 (0.6%)	1
Congenital, familial and genetic disorders
Double ureter	1/166 (0.6%)	1	0/162 (0%)	0
Kidney duplex	1/166 (0.6%)	1	0/162 (0%)	0
Endocrine disorders
Hyperthyroidism	0/166 (0%)	0	1/162 (0.6%)	1
Gastrointestinal disorders
Abdominal pain	1/166 (0.6%)	1	0/162 (0%)	0
Colitis ulcerative	1/166 (0.6%)	1	0/162 (0%)	0
Constipation	2/166 (1.2%)	2	1/162 (0.6%)	1
Diarrhoea	2/166 (1.2%)	2	1/162 (0.6%)	1
Vomiting	2/166 (1.2%)	2	0/162 (0%)	0
General disorders
Catheter site pain	0/166 (0%)	0	1/162 (0.6%)	1
Face oedema	1/166 (0.6%)	1	0/162 (0%)	0
Hyperpyrexia	1/166 (0.6%)	1	0/162 (0%)	0
Pain	0/166 (0%)	0	5/162 (3.1%)	5
Pyrexia	3/166 (1.8%)	3	1/162 (0.6%)	1
Infections and infestations
Cystitis	2/166 (1.2%)	2	5/162 (3.1%)	5
Pyelonephritis	1/166 (0.6%)	1	0/162 (0%)	0
Skin infection	1/166 (0.6%)	1	0/162 (0%)	0
Urethritis	2/166 (1.2%)	2	1/162 (0.6%)	1
Injury, poisoning and procedural complications
Post procedural haemorrhage	0/166 (0%)	0	3/162 (1.9%)	3
Post procedural nausea	1/166 (0.6%)	1	0/162 (0%)	0
Post procedural vomiting	1/166 (0.6%)	1	0/162 (0%)	0
Procedural pain	4/166 (2.4%)	4	0/162 (0%)	0
Investigations
Body temperature increased	0/166 (0%)	0	1/162 (0.6%)	1
Metabolism and nutrition disorders
Gout	1/166 (0.6%)	1	0/162 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	0/166 (0%)	0	1/162 (0.6%)	1
Neck pain	0/166 (0%)	0	2/162 (1.2%)	2
Pain in extremity	0/166 (0%)	0	1/162 (0.6%)	1
Shoulder pain	0/166 (0%)	0	1/162 (0.6%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer	0/166 (0%)	0	1/162 (0.6%)	1
Nervous system disorders
Anticholinergic syndrome	1/166 (0.6%)	1	0/162 (0%)	0
Cerebrovascular accident	1/166 (0.6%)	1	0/162 (0%)	0
Dizziness postural	0/166 (0%)	0	1/162 (0.6%)	1
Headache	3/166 (1.8%)	3	0/162 (0%)	0
Psychiatric disorders
Restlessness	0/166 (0%)	0	1/162 (0.6%)	2
Sleep disorder	1/166 (0.6%)	1	3/162 (1.9%)	3
Renal and urinary disorders
Bladder diverticulum	0/166 (0%)	0	1/162 (0.6%)	1
Bladder pain	5/166 (3%)	6	3/162 (1.9%)	4
Bladder spasm	1/166 (0.6%)	1	4/162 (2.5%)	4
Dysuria	1/166 (0.6%)	1	2/162 (1.2%)	2
Haematuria	1/166 (0.6%)	1	0/162 (0%)	0
Haemorrhage urinary tract	0/166 (0%)	0	1/162 (0.6%)	1
Micturition urgency	1/166 (0.6%)	1	0/162 (0%)	0
Renal pain	1/166 (0.6%)	1	0/162 (0%)	0
Ureteric stenosis	1/166 (0.6%)	1	0/162 (0%)	0
Urethral meatus stenosis	1/166 (0.6%)	1	0/162 (0%)	0
Urethral stricture	0/166 (0%)	0	1/162 (0.6%)	1
Urge incontinence	1/166 (0.6%)	1	1/162 (0.6%)	1
Vesical tenesmus	1/166 (0.6%)	1	1/162 (0.6%)	1
Skin and subcutaneous tissue disorders
Alopecia	2/166 (1.2%)	2	0/162 (0%)	0
Alopecia areata	1/166 (0.6%)	1	0/162 (0%)	0
Dermatitis allergic	1/166 (0.6%)	1	0/162 (0%)	0
Pruritus	1/166 (0.6%)	1	0/162 (0%)	0
Rash	1/166 (0.6%)	1	1/162 (0.6%)	1
Skin reaction	0/166 (0%)	0	1/162 (0.6%)	1
Surgical and medical procedures
Urinary bladder excision	0/166 (0%)	0	1/162 (0.6%)	1
Vascular disorders
Haemorrhage	1/166 (0.6%)	1	2/162 (1.2%)	2
Hypertension	1/166 (0.6%)	1	0/162 (0%)	0

Limitations/Caveats

The study was stopped early for futility reasons. In addition, due to limitations in this databank, some original outcome measures are not disclosed. Time to Recurrence and Recurrence-Free Survival in Subgroups had data that were un-estimated.

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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 more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.