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S0337, Gemcitabine After Surgery in Treating Patients With Newly Diagnosed or Recurrent Bladder Cancer

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ClinicalTrials.gov Identifier: NCT00445601
Recruitment Status : Completed
First Posted : March 9, 2007
Results First Posted : April 24, 2018
Last Update Posted : April 24, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Southwest Oncology Group

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Bladder Cancer
Interventions Drug: gemcitabine hydrochloride
Other: placebo
Enrollment 406
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Arm I Arm II
Hide Arm/Group Description

Patients receive intravesical gemcitabine hydrochloride over 1 hour post-TURBT.

gemcitabine hydrochloride: Given intravesically

Patients receive intravesical placebo over 1 hour post-TURBT.

placebo: Given intravesically

Period Title: Overall Study
Started [1] 201 205
Received TURBT 190 193
Completed [2] 168 177
Not Completed 33 28
Reason Not Completed
Withdrawal by Subject             11             11
TURBT Complication             12             8
Incorrect Disease Status             6             6
Drug Delivery Issue             2             2
Adverse Event             2             0
Death prior to TURBT             0             1
[1]
Randomized to Treatment Arm
[2]
Received Drug Instillation
Arm/Group Title Arm I Arm II Total
Hide Arm/Group Description

Patients receive intravesical gemcitabine hydrochloride over 1 hour post-TURBT.

gemcitabine hydrochloride: Given intravesically

Patients receive intravesical placebo over 1 hour post-TURBT.

placebo: Given intravesically

Total of all reporting groups
Overall Number of Baseline Participants 201 205 406
Hide Baseline Analysis Population Description
All eligible patients
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 201 participants 205 participants 406 participants
66
(38 to 97)
66
(35 to 93)
66
(35 to 97)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 201 participants 205 participants 406 participants
Female
38
  18.9%
24
  11.7%
62
  15.3%
Male
163
  81.1%
181
  88.3%
344
  84.7%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Race Number Analyzed 201 participants 205 participants 406 participants
White
186
  92.5%
185
  90.2%
371
  91.4%
Black
6
   3.0%
9
   4.4%
15
   3.7%
Asian
4
   2.0%
5
   2.4%
9
   2.2%
Native American
0
   0.0%
2
   1.0%
2
   0.5%
Unknown
5
   2.5%
4
   2.0%
9
   2.2%
Occurence status  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 201 participants 205 participants 406 participants
First Occurence
128
  63.7%
128
  62.4%
256
  63.1%
Recurrent
66
  32.8%
77
  37.6%
143
  35.2%
Unknown
7
   3.5%
0
   0.0%
7
   1.7%
Number of tumors  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 201 participants 205 participants 406 participants
1
135
  67.2%
140
  68.3%
275
  67.7%
>= 2
66
  32.8%
65
  31.7%
131
  32.3%
Prior intravesical therapy  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 201 participants 205 participants 406 participants
Yes
39
  19.4%
39
  19.0%
78
  19.2%
No
162
  80.6%
166
  81.0%
328
  80.8%
Zubrod Performance Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 201 participants 205 participants 406 participants
0
157
  78.1%
165
  80.5%
322
  79.3%
1
44
  21.9%
40
  19.5%
84
  20.7%
[1]
Measure Description:

Zubrod Performance Status Scale:

0. Fully active, able to carry on all pre-disease performance without restriction.

  1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework, office work.
  2. Ambulatory and capable of self-care but unable to carry out any work activities; up and about more than 50% of waking hours.
  3. Capable of limited self-care, confined to bed or chair more than 50% of waking hours.
  4. Completely disabled; cannot carry on any self-care; totally confined to bed or chair.
Smoking history  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 201 participants 205 participants 406 participants
Current
49
  24.4%
54
  26.3%
103
  25.4%
Prior
98
  48.8%
101
  49.3%
199
  49.0%
Never
54
  26.9%
46
  22.4%
100
  24.6%
Unknown
0
   0.0%
4
   2.0%
4
   1.0%
1.Primary Outcome
Title Disease Recurrence Rate
Hide Description Percentage of patients who experienced a recurrence of grade 1 or 2 superficial transitional cell cancer of the bladder between the date of registration and 24 months. Disease recurrence considered to occur at date of first observation of recurrent disease subsequently confirmed by biopsy. Patients without recurrence were censored at the time of their last cystoscopy.
Time Frame Up to 2 Years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat population
Arm/Group Title Arm I Arm II
Hide Arm/Group Description:

Patients receive intravesical gemcitabine hydrochloride over 1 hour.

gemcitabine hydrochloride: Given intravesically

Patients receive intravesical placebo over 1 hour.

placebo: Given intravesically

Overall Number of Participants Analyzed 201 205
Measure Type: Number
Unit of Measure: percentage of patients with recurrence
27.86 40
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm I, Arm II
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.01
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.66
Confidence Interval (2-Sided) 95%
0.48 to 0.90
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Rate of Progression to Muscle Invasive Disease at 4 Years
Hide Description From date of registration to date of diagnosis of progressive disease. Censor at date of last disease assessment for those without progression.
Time Frame 4 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Population
Arm/Group Title Arm I Arm II
Hide Arm/Group Description:

Patients receive intravesical gemcitabine hydrochloride over 1 hour post-TURBT.

gemcitabine hydrochloride: Given intravesically

Patients receive intravesical placebo over 1 hour post-TURBT.

placebo: Given intravesically

Overall Number of Participants Analyzed 201 205
Measure Type: Number
Unit of Measure: percentage of patients with progression
2.49 4.39
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm I, Arm II
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.23
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.51
Confidence Interval (2-Sided) 95%
0.18 to 1.49
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Compare Qualitative and Quantitative Toxicities Between the Treatment Arms
Hide Description Number of patients with Grade 3 through Grade 5 adverse events that are related to study drug
Time Frame Up to 4 years after Transurethral Resection of Bladder Tumor (TURBT)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All eligible patients who received instillation after TURBT and reported adverse events
Arm/Group Title Arm I: Gemcitabine Arm II: Placebo
Hide Arm/Group Description:
Patients receive intravesical gemcitabine hydrochloride over 1 hour post-TURBT.
Patients receive intravesical placebo over 1 hour post -TURBT.
Overall Number of Participants Analyzed 165 174
Measure Type: Number
Unit of Measure: Participants
Bladder spasms 0 1
Hemorrhage, GU - Bladder 1 0
Hemorrhage, GU - Urinary NOS 2 1
Infection-Other (Specify) 1 0
Pain - Bladder 0 1
Pain - Urethra 0 1
Urinary frequency/urgency 0 2
4.Secondary Outcome
Title Rate of Disease Worsening Over 2 Years
Hide Description Compare whether treatment with post-TURBT intravesical instillation of gemcitabine vs placebo results in reduced long-term morbidity in patients, as defined by requirement for fewer TURBTs, courses of traditional intravesical therapies, and surveillance cystoscopies over 4 years.
Time Frame Up to 2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
TURBT data after patients stopped trial was not collected.
Arm/Group Title Arm I: Gemcitabine Arm II: Placebo
Hide Arm/Group Description:
Patients receive intravesical gemcitabine hydrochloride over 1 hour post-TURBT.
Patients receive intravesical placebo over 1 hour post -TURBT.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame Assessed every 3 months for 2 years, then every 6 months for 2 years
Adverse Event Reporting Description Participants were monitored for toxicity at Week 1 and 2 after protocol treatment, with an additional assessment at Week 4 if any toxicities noted during the first two weeks. Patients were then monitored every 3 weeks for the first 2 years following protocol treatment, and then every 6 months for the following 2 years (up to 4 years).
 
Arm/Group Title Arm I: Gemcitabine Arm II: Placebo
Hide Arm/Group Description Patients receive intravesical gemcitabine hydrochloride over 1 hour post-TURBT. Patients receive intravesical placebo over 1 hour post-TURBT.
All-Cause Mortality
Arm I: Gemcitabine Arm II: Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   17/201 (8.46%)   25/205 (12.20%) 
Show Serious Adverse Events Hide Serious Adverse Events
Arm I: Gemcitabine Arm II: Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   7/165 (4.24%)   5/174 (2.87%) 
Cardiac disorders     
Cardiac General-Other  1  1/165 (0.61%)  0/174 (0.00%) 
Infections and infestations     
Infection with unknown ANC - Blood  1  0/165 (0.00%)  1/174 (0.57%) 
Infection with unknown ANC - Urinary tract NOS  1  0/165 (0.00%)  1/174 (0.57%) 
Infection-Other  1  1/165 (0.61%)  0/174 (0.00%) 
Metabolism and nutrition disorders     
Glucose, serum-high (hyperglycemia)  1  1/165 (0.61%)  0/174 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Tumor flare  1  0/165 (0.00%)  1/174 (0.57%) 
Nervous system disorders     
CNS cerebrovascular ischemia  1  1/165 (0.61%)  0/174 (0.00%) 
Vasovagal episode  1  1/165 (0.61%)  0/174 (0.00%) 
Renal and urinary disorders     
Hemorrhage, GU - Bladder  1  2/165 (1.21%)  0/174 (0.00%) 
Hemorrhage, GU - Urinary NOS  1  0/165 (0.00%)  1/174 (0.57%) 
Obstruction, GU - Bladder  1  0/165 (0.00%)  1/174 (0.57%) 
Obstruction, GU - Ureter  1  1/165 (0.61%)  0/174 (0.00%) 
Pain - Bladder  1  1/165 (0.61%)  0/174 (0.00%) 
Renal failure  1  1/165 (0.61%)  0/174 (0.00%) 
1
Term from vocabulary, CTCAE (3.0)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Arm I: Gemcitabine Arm II: Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   60/165 (36.36%)   58/174 (33.33%) 
Gastrointestinal disorders     
Nausea  1  11/165 (6.67%)  3/174 (1.72%) 
Vomiting  1  9/165 (5.45%)  1/174 (0.57%) 
Renal and urinary disorders     
Bladder spasms  1  13/165 (7.88%)  9/174 (5.17%) 
Hemorrhage, GU - Urinary NOS  1  16/165 (9.70%)  19/174 (10.92%) 
Pain - Bladder  1  23/165 (13.94%)  23/174 (13.22%) 
Urinary frequency/urgency  1  25/165 (15.15%)  25/174 (14.37%) 
Urinary retention (including neurogenic bladder)  1  9/165 (5.45%)  10/174 (5.75%) 
1
Term from vocabulary, CTCAE (3.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Catherine Tangen, Genitourinary Committee Statistician
Organization: SWOG Statistics and Data Management Center
Phone: 206-667-2933
Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT00445601     History of Changes
Other Study ID Numbers: CDR0000534235
S0337 ( Other Identifier: SWOG )
U10CA032102 ( U.S. NIH Grant/Contract )
First Submitted: March 7, 2007
First Posted: March 9, 2007
Results First Submitted: December 21, 2017
Results First Posted: April 24, 2018
Last Update Posted: April 24, 2018