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Phase II Pazopanib in Combination With Weekly Paclitaxel in Refractory Urothelial Cancer

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ClinicalTrials.gov Identifier: NCT01108055
Recruitment Status : Completed
First Posted : April 21, 2010
Results First Posted : June 9, 2017
Last Update Posted : June 9, 2017
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Sandy Srinivas, Stanford University

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Bladder Cancer
Bladder (Urothelial, Transitional Cell) Cancer
Bladder (Urothelial, Transitional Cell) Cancer Superficial (Non-Invasive)
Bladder (Urothelial, Transitional Cell) Cancer Resectable (Pre-Cystectomy)
Bladder (Urothelial, Transitional Cell) Cancer Metastatic or Unresectable
Interventions Drug: Pazopanib (GW786034)
Drug: Paclitaxel
Enrollment 43
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Pazopanib + Paclitaxel
Hide Arm/Group Description A trial combining paclitaxel with pazopanib, a commonly used anti-angiogenic agent with significant anti-tumor activity in various solid tumors.
Period Title: Overall Study
Started 43
Eligible and Started Treatment 32
Completed 28
Not Completed 15
Reason Not Completed
Ineligible             11
Not evaluable- didn't complete treatment             4
Arm/Group Title Pazopanib + Paclitaxel
Hide Arm/Group Description A trial combining paclitaxel with pazopanib, a commonly used anti-angiogenic agent with significant anti-tumor activity in various solid tumors.
Overall Number of Baseline Participants 32
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 32 participants
67
(29 to 89)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants
Female
9
  28.1%
Male
23
  71.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants
Hispanic or Latino
1
   3.1%
Not Hispanic or Latino
30
  93.8%
Unknown or Not Reported
1
   3.1%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants
American Indian or Alaska Native
0
   0.0%
Asian
4
  12.5%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
3
   9.4%
White
23
  71.9%
More than one race
0
   0.0%
Unknown or Not Reported
2
   6.3%
Prior Treatment Cycles   [1] 
Median (Full Range)
Unit of measure:  Cycles
Number Analyzed 32 participants
4
(1 to 14)
[1]
Measure Description: A full treatment cycle is defined as 28 days.
Sites of Primary Tumor  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants
Bladder
15
  46.9%
Renal Pelvis
11
  34.4%
Ureter
6
  18.8%
Number of prior chemotherapies  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants
1
13
  40.6%
2
19
  59.4%
Time from last chemotherapy  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants
< 3 months
15
  46.9%
> 3 months
17
  53.1%
Bellmunt Score  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants
0
7
  21.9%
1
14
  43.8%
2
11
  34.4%
3
0
   0.0%
1.Primary Outcome
Title Objective Tumor Response
Hide Description

The tumor response rate was assessed per the Response Evaluation Criteria In Solid Tumors (RECIST). RECIST criteria are a set of published rules that define when cancer patients improve ("respond"); stay the same ("stable"); or worsen ("progression") during treatments. RECIST criteria offer a simplified and conservative extraction of imaging data suitable for wide application in clinical trials. The criteria presume that linear measures are an adequate substitute for 2-dimensional (2D) methods and includes 4 response categories:

  • Complete response (CR) = Disappearance of all target lesions
  • Partial response (PR) = 30% decrease in the sum of the longest diameter of target lesions
  • Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions
  • Stable disease (SD) = Small changes that do not meet above criteria Objective tumor response means those with response better than stable disease, ie, complete response (CR) + partial response (PR).
Time Frame Every 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The outcome is reported as subjects with CR (complete response) + PR (partial response).
Arm/Group Title Pazopanib + Paclitaxel
Hide Arm/Group Description:
A trial combining paclitaxel with pazopanib, a commonly used anti-angiogenic agent with significant anti-tumor activity in various solid tumors.
Overall Number of Participants Analyzed 32
Measure Type: Count of Participants
Unit of Measure: Participants
15
  46.9%
2.Secondary Outcome
Title Progression-free Survival (PFS)
Hide Description [Not Specified]
Time Frame 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pazopanib + Paclitaxel
Hide Arm/Group Description:
A trial combining paclitaxel with pazopanib, a commonly used anti-angiogenic agent with significant anti-tumor activity in various solid tumors.
Overall Number of Participants Analyzed 32
Median (95% Confidence Interval)
Unit of Measure: Months
6.2
(5.6 to 7.6)
3.Secondary Outcome
Title Overall Response Rate
Hide Description

The tumor response rate was assessed per the Response Evaluation Criteria In Solid Tumors (RECIST). RECIST criteria are a set of published rules that define when cancer patients improve ("respond"); stay the same ("stable"); or worsen ("progression") during treatments. RECIST criteria offer a simplified and conservative extraction of imaging data suitable for wide application in clinical trials. The criteria presume that linear measures are an adequate substitute for 2-dimensional (2D) methods and includes 4 response categories:

  • Complete response (CR) = Disappearance of all target lesions
  • Partial response (PR) = 30% decrease in the sum of the longest diameter of target lesions
  • Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions
  • Stable disease (SD) = Small changes that do not meet above criteria Tumor response rate by each response criteria.
Time Frame 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
Does not include participants who did not complete 2 cycles of treatment.
Arm/Group Title Pazopanib + Paclitaxel
Hide Arm/Group Description:
A trial combining paclitaxel with pazopanib, a commonly used anti-angiogenic agent with significant anti-tumor activity in various solid tumors.
Overall Number of Participants Analyzed 28
Measure Type: Count of Participants
Unit of Measure: Participants
Complete Response (CR)
3
  10.7%
Partial Response (PR)
12
  42.9%
Stable Disease (SD)
11
  39.3%
Progressive Disease (PD)
2
   7.1%
4.Secondary Outcome
Title Overall Survival
Hide Description Overall survival is reported as the median survival of the evaluable subjects (ie, completed 2 cycles of treatment).
Time Frame 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
Does not include participants who did not complete 2 cycles of treatment.
Arm/Group Title Pazopanib + Paclitaxel
Hide Arm/Group Description:
A trial combining paclitaxel with pazopanib, a commonly used anti-angiogenic agent with significant anti-tumor activity in various solid tumors.
Overall Number of Participants Analyzed 28
Mean (95% Confidence Interval)
Unit of Measure: Months
10
(5.7 to 16)
5.Secondary Outcome
Title Median Overall Survival (OS) by Bellmunt Score
Hide Description

Comparison between the participant's baseline Bellmunt prognostic risk factor score and survival rates.

The Bellmunt prognostic risk factor score is a tool that is often used to predict treatment outcomes before initiating a secondline treatment regimen.

The risk factors used to calculate the Bellmunt score include:

  • Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1
  • Presence of liver metastases
  • Presence of visceral involvement (defined as liver, lung, bone or any non-lymph node)
  • Lymph node-only involvement
  • Hemoglobin concentration < 10 g/dL

The score is calculated based on the presence of 0; 1; 2; or 3 of the above prognostic factors. This outcome reports median overall survival based on whether the participant had 0; 1; 2; or 3 prognostic factors.

Time Frame 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
Include all 32 participants, regardless of completing 2 cycles of treatment.
Arm/Group Title Pazopanib + Paclitaxel
Hide Arm/Group Description:
A trial combining paclitaxel with pazopanib, a commonly used anti-angiogenic agent with significant anti-tumor activity in various solid tumors.
Overall Number of Participants Analyzed 32
Median (Full Range)
Unit of Measure: Months
Bellmunt Score of 0 Number Analyzed 7 participants
13.8
(6 to 24)
Bellmunt Score of 1 Number Analyzed 14 participants
8
(2 to 55)
Bellmunt Score of 2 Number Analyzed 11 participants
7.7
(1 to 21)
Bellmunt Score of 3 Number Analyzed 0 participants
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Pazopanib + Paclitaxel
Hide Arm/Group Description A trial combining paclitaxel with pazopanib, a commonly used anti-angiogenic agent with significant anti-tumor activity in various solid tumors.
All-Cause Mortality
Pazopanib + Paclitaxel
Affected / at Risk (%)
Total   --/--    
Hide Serious Adverse Events
Pazopanib + Paclitaxel
Affected / at Risk (%) # Events
Total   15/32 (46.88%)    
Gastrointestinal disorders   
gastrointestinal fistula * 1  1/32 (3.13%)  1
General disorders   
Fever * 1  2/32 (6.25%)  2
Infections and infestations   
febrile neutropenia * 1  2/32 (6.25%)  2
infection with grade 3 or 4 neutrophils * 1  2/32 (6.25%)  2
bacterial pneumonia * 1  1/32 (3.13%)  1
infection with normal ANC * 1  1/32 (3.13%)  1
sepsis * 1  1/32 (3.13%)  1
Investigations   
electrolyte imbalance * 1  1/32 (3.13%)  1
Musculoskeletal and connective tissue disorders   
Cord compression * 1  1/32 (3.13%)  1
Back Pain * 1  1/32 (3.13%)  1
Nervous system disorders   
Seizure * 1  1/32 (3.13%)  1
Skin and subcutaneous tissue disorders   
wound complication, non infectious * 1  1/32 (3.13%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, CTCAE3
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Pazopanib + Paclitaxel
Affected / at Risk (%) # Events
Total   20/32 (62.50%)    
Blood and lymphatic system disorders   
lukocytes * 1  9/32 (28.13%)  12
Platelets * 1  8/32 (25.00%)  16
Neutrophils/granulocytes * 1  4/32 (12.50%)  8
anemia * 1  6/32 (18.75%)  16
lymphopenia * 1  6/32 (18.75%)  27
hemolysis * 1  2/32 (6.25%)  2
Edema: head and neck * 1  1/32 (3.13%)  1
Edema: limb * 1  1/32 (3.13%)  1
Cardiac disorders   
hypertension * 1  3/32 (9.38%)  3
Ear and labyrinth disorders   
Hearing: patients without baseline audiogram and not enrolled in a monitoring program * 1  1/32 (3.13%)  1
Tinnitus * 1  1/32 (3.13%)  1
Eye disorders   
vision-flashing lights/floaters * 1  1/32 (3.13%)  1
Gastrointestinal disorders   
anorexia * 1  8/32 (25.00%)  9
diarrhea * 1  5/32 (15.63%)  8
nausea * 1  4/32 (12.50%)  6
Vomiting * 1  4/32 (12.50%)  5
Constipation * 1  3/32 (9.38%)  3
dysgeusia * 1  3/32 (9.38%)  4
Distension/bloating, abdominal * 1  2/32 (6.25%)  2
Mucositis/stomatitis - oral cavity * 1  2/32 (6.25%)  2
salivary gland changes/saliva * 1  2/32 (6.25%)  2
Dehydration * 1  1/32 (3.13%)  1
GI, other * 1  1/32 (3.13%)  1
hemorrhage, GI - Varices * 1  1/32 (3.13%)  1
General disorders   
Fatigue * 1  15/32 (46.88%)  35
Insomnia * 1  2/32 (6.25%)  2
pain, back * 1  6/32 (18.75%)  7
Pain, abdomen NOS * 1  5/32 (15.63%)  7
Pain, head/headache * 1  4/32 (12.50%)  4
Pain, chest/thorax NOS * 1  3/32 (9.38%)  3
Pain Extremity-limb * 1  2/32 (6.25%)  2
Pain, chest wall * 1  1/32 (3.13%)  1
Pain, oral cavity * 1  1/32 (3.13%)  1
hemorrhage/bleeding * 1  2/32 (6.25%)  5
growth and development- other * 1  1/32 (3.13%)  1
Infections and infestations   
fever * 1  1/32 (3.13%)  1
Infection with unknown ANC - Bladder * 1  1/32 (3.13%)  1
Infection with unknown ANC - Sinus * 1  1/32 (3.13%)  1
infection with unknown ANC - Urinary tract NOS * 1  1/32 (3.13%)  1
Investigations   
Creatinine, increased * 1  7/32 (21.88%)  13
Alt, SGPT * 1  6/32 (18.75%)  8
hyperglycemia * 1  6/32 (18.75%)  9
hypoalbuminemia * 1  5/32 (15.63%)  7
hypocalcemia * 1  4/32 (12.50%)  8
hypokalemia * 1  4/32 (12.50%)  7
alkaline phosphatase * 1  3/32 (9.38%)  4
hypomagnesemia * 1  3/32 (9.38%)  3
hyponatremia * 1  3/32 (9.38%)  5
hyperbilirubinemia * 1  2/32 (6.25%)  2
hyperkalemia * 1  2/32 (6.25%)  4
proteinuria * 1  2/32 (6.25%)  2
Bicarbonate, serum-low * 1  1/32 (3.13%)  1
Glomerular Filtration rate * 1  1/32 (3.13%)  4
hypophosphatemia * 1  1/32 (3.13%)  1
Metabolism and nutrition disorders   
Weight loss * 1  4/32 (12.50%)  5
Musculoskeletal and connective tissue disorders   
Musculoskeletal/Soft Tissue - other * 1  2/32 (6.25%)  2
muscle weakness, extraocular * 1  1/32 (3.13%)  1
muscle weakness, whole body/generalized * 1  1/32 (3.13%)  1
Nervous system disorders   
Neuropathy: sensory * 1  7/32 (21.88%)  9
Dizziness * 1  5/32 (15.63%)  5
Cognitive distrubance * 1  1/32 (3.13%)  1
memory impariment * 1  1/32 (3.13%)  1
Mood alteration - Anxeity * 1  1/32 (3.13%)  1
Renal and urinary disorders   
hemorrhage, GU - bladder * 1  1/32 (3.13%)  1
Hemorrhage, GU - Urinary NOS * 1  1/32 (3.13%)  1
Reproductive system and breast disorders   
gynecomastia * 1  1/32 (3.13%)  1
Respiratory, thoracic and mediastinal disorders   
Dyspnea * 1  7/32 (21.88%)  10
pneumonitis/pulmonary infiltrates * 1  2/32 (6.25%)  3
Cough * 1  1/32 (3.13%)  1
Hiccoughs * 1  1/32 (3.13%)  1
hypoxia * 1  1/32 (3.13%)  1
pulmonary/upper respiratory * 1  1/32 (3.13%)  1
Voice changes/dysarthria * 1  1/32 (3.13%)  1
Hemorrhage, pulmonary/upper respiratory - Nose * 1  1/32 (3.13%)  1
Skin and subcutaneous tissue disorders   
diaphoresis * 1  2/32 (6.25%)  2
Hair loss/alopecia * 1  4/32 (12.50%)  4
Rash: acne/acneiform * 1  2/32 (6.25%)  2
Rash: erythema multiforme * 1  2/32 (6.25%)  4
bruising (in absence of grade 3 or 4 thrombocytopenia) * 1  1/32 (3.13%)  1
Dry Skin * 1  1/32 (3.13%)  1
hypopigmentation * 1  1/32 (3.13%)  1
injection site reaction/extravasation changes * 1  1/32 (3.13%)  2
Nail Changes * 1  1/32 (3.13%)  1
Rash/desquamation * 1  1/32 (3.13%)  1
Rash: hand-foot skin reaction * 1  1/32 (3.13%)  1
Skin breakdown/decubitus ulcer * 1  1/32 (3.13%)  1
Vascular disorders   
Thrombosis/thrombus/embolism * 1  3/32 (9.38%)  4
vascular - other * 1  1/32 (3.13%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, CTCAE3
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
Layout table for Results Point of Contact information
Name/Title: Sandy Srinivas, MD
Organization: Stanford University
Phone: 650 498 6000
EMail: sandysri@stanford.edu
Layout table for additonal information
Responsible Party: Sandy Srinivas, Stanford University
ClinicalTrials.gov Identifier: NCT01108055    
Other Study ID Numbers: IRB-17472
SU-04152010-5683 ( Other Identifier: Stanford University )
BLDR0010 ( Other Identifier: OnCore )
First Submitted: April 15, 2010
First Posted: April 21, 2010
Results First Submitted: January 18, 2017
Results First Posted: June 9, 2017
Last Update Posted: June 9, 2017