Trial Outcomes & Findings for Phase II Pazopanib in Combination With Weekly Paclitaxel in Refractory Urothelial Cancer (NCT NCT01108055)

NCT ID: NCT01108055

Last Updated: 2017-06-09

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

43 participants

Primary outcome timeframe

Every 8 weeks

Results posted on

2017-06-09

Participant Flow

Participant milestones

Participant milestones
Measure
Pazopanib + Paclitaxel
A trial combining paclitaxel with pazopanib, a commonly used anti-angiogenic agent with significant anti-tumor activity in various solid tumors.
Overall Study
STARTED
43
Overall Study
Eligible and Started Treatment
32
Overall Study
COMPLETED
28
Overall Study
NOT COMPLETED
15

Reasons for withdrawal

Reasons for withdrawal
Measure
Pazopanib + Paclitaxel
A trial combining paclitaxel with pazopanib, a commonly used anti-angiogenic agent with significant anti-tumor activity in various solid tumors.
Overall Study
Ineligible
11
Overall Study
Not evaluable- didn't complete treatment
4

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Pazopanib + Paclitaxel
n=32 Participants
A trial combining paclitaxel with pazopanib, a commonly used anti-angiogenic agent with significant anti-tumor activity in various solid tumors.
Age, Continuous
67 years
n=5 Participants
Sex: Female, Male
Female
9 Participants
n=5 Participants
Sex: Female, Male
Male
23 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
1 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
30 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
1 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
Race (NIH/OMB)
Asian
4 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
3 Participants
n=5 Participants
Race (NIH/OMB)
White
23 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
2 Participants
n=5 Participants
Prior Treatment Cycles
4 Cycles
n=5 Participants
Sites of Primary Tumor
Bladder
15 Participants
n=5 Participants
Sites of Primary Tumor
Renal Pelvis
11 Participants
n=5 Participants
Sites of Primary Tumor
Ureter
6 Participants
n=5 Participants
Number of prior chemotherapies
1
13 Participants
n=5 Participants
Number of prior chemotherapies
2
19 Participants
n=5 Participants
Time from last chemotherapy
< 3 months
15 Participants
n=5 Participants
Time from last chemotherapy
> 3 months
17 Participants
n=5 Participants
Bellmunt Score
0
7 Participants
n=5 Participants
Bellmunt Score
1
14 Participants
n=5 Participants
Bellmunt Score
2
11 Participants
n=5 Participants
Bellmunt Score
3
0 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Every 8 weeks

Population: The outcome is reported as subjects with CR (complete response) + PR (partial response).

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).

Outcome measures

Outcome measures
Measure
Pazopanib + Paclitaxel
n=32 Participants
A trial combining paclitaxel with pazopanib, a commonly used anti-angiogenic agent with significant anti-tumor activity in various solid tumors.
Objective Tumor Response
15 Participants

SECONDARY outcome

Timeframe: 4 years

Outcome measures

Outcome measures
Measure
Pazopanib + Paclitaxel
n=32 Participants
A trial combining paclitaxel with pazopanib, a commonly used anti-angiogenic agent with significant anti-tumor activity in various solid tumors.
Progression-free Survival (PFS)
6.2 Months
Interval 5.6 to 7.6

SECONDARY outcome

Timeframe: 4 years

Population: Does not include participants who did not complete 2 cycles of treatment.

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.

Outcome measures

Outcome measures
Measure
Pazopanib + Paclitaxel
n=28 Participants
A trial combining paclitaxel with pazopanib, a commonly used anti-angiogenic agent with significant anti-tumor activity in various solid tumors.
Overall Response Rate
Complete Response (CR)
3 Participants
Overall Response Rate
Partial Response (PR)
12 Participants
Overall Response Rate
Stable Disease (SD)
11 Participants
Overall Response Rate
Progressive Disease (PD)
2 Participants

SECONDARY outcome

Timeframe: 4 years

Population: Does not include participants who did not complete 2 cycles of treatment.

Overall survival is reported as the median survival of the evaluable subjects (ie, completed 2 cycles of treatment).

Outcome measures

Outcome measures
Measure
Pazopanib + Paclitaxel
n=28 Participants
A trial combining paclitaxel with pazopanib, a commonly used anti-angiogenic agent with significant anti-tumor activity in various solid tumors.
Overall Survival
10 Months
Interval 5.7 to 16.0

SECONDARY outcome

Timeframe: 4 years

Population: Include all 32 participants, regardless of completing 2 cycles of treatment.

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.

Outcome measures

Outcome measures
Measure
Pazopanib + Paclitaxel
n=32 Participants
A trial combining paclitaxel with pazopanib, a commonly used anti-angiogenic agent with significant anti-tumor activity in various solid tumors.
Median Overall Survival (OS) by Bellmunt Score
Bellmunt Score of 0
13.8 Months
Interval 6.0 to 24.0
Median Overall Survival (OS) by Bellmunt Score
Bellmunt Score of 1
8 Months
Interval 2.0 to 55.0
Median Overall Survival (OS) by Bellmunt Score
Bellmunt Score of 2
7.7 Months
Interval 1.0 to 21.0

Adverse Events

Pazopanib + Paclitaxel

Serious events: 15 serious events
Other events: 20 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Pazopanib + Paclitaxel
n=32 participants at risk
A trial combining paclitaxel with pazopanib, a commonly used anti-angiogenic agent with significant anti-tumor activity in various solid tumors.
Investigations
electrolyte imbalance
3.1%
1/32 • Number of events 1
Skin and subcutaneous tissue disorders
wound complication, non infectious
3.1%
1/32 • Number of events 1
Gastrointestinal disorders
gastrointestinal fistula
3.1%
1/32 • Number of events 1
Infections and infestations
febrile neutropenia
6.2%
2/32 • Number of events 2
Infections and infestations
infection with grade 3 or 4 neutrophils
6.2%
2/32 • Number of events 2
General disorders
Fever
6.2%
2/32 • Number of events 2
Infections and infestations
bacterial pneumonia
3.1%
1/32 • Number of events 1
Infections and infestations
infection with normal ANC
3.1%
1/32 • Number of events 1
Musculoskeletal and connective tissue disorders
Cord compression
3.1%
1/32 • Number of events 1
Nervous system disorders
Seizure
3.1%
1/32 • Number of events 1
Musculoskeletal and connective tissue disorders
Back Pain
3.1%
1/32 • Number of events 1
Infections and infestations
sepsis
3.1%
1/32 • Number of events 1

Other adverse events

Other adverse events
Measure
Pazopanib + Paclitaxel
n=32 participants at risk
A trial combining paclitaxel with pazopanib, a commonly used anti-angiogenic agent with significant anti-tumor activity in various solid tumors.
General disorders
Fatigue
46.9%
15/32 • Number of events 35
Metabolism and nutrition disorders
Weight loss
12.5%
4/32 • Number of events 5
General disorders
Insomnia
6.2%
2/32 • Number of events 2
Skin and subcutaneous tissue disorders
diaphoresis
6.2%
2/32 • Number of events 2
Infections and infestations
fever
3.1%
1/32 • Number of events 1
Gastrointestinal disorders
anorexia
25.0%
8/32 • Number of events 9
Gastrointestinal disorders
diarrhea
15.6%
5/32 • Number of events 8
Gastrointestinal disorders
nausea
12.5%
4/32 • Number of events 6
Gastrointestinal disorders
Vomiting
12.5%
4/32 • Number of events 5
Gastrointestinal disorders
Constipation
9.4%
3/32 • Number of events 3
Gastrointestinal disorders
dysgeusia
9.4%
3/32 • Number of events 4
Gastrointestinal disorders
Distension/bloating, abdominal
6.2%
2/32 • Number of events 2
Gastrointestinal disorders
Mucositis/stomatitis - oral cavity
6.2%
2/32 • Number of events 2
Gastrointestinal disorders
salivary gland changes/saliva
6.2%
2/32 • Number of events 2
Gastrointestinal disorders
Dehydration
3.1%
1/32 • Number of events 1
Gastrointestinal disorders
GI, other
3.1%
1/32 • Number of events 1
Blood and lymphatic system disorders
lukocytes
28.1%
9/32 • Number of events 12
Blood and lymphatic system disorders
Platelets
25.0%
8/32 • Number of events 16
Blood and lymphatic system disorders
Neutrophils/granulocytes
12.5%
4/32 • Number of events 8
Blood and lymphatic system disorders
anemia
18.8%
6/32 • Number of events 16
Blood and lymphatic system disorders
lymphopenia
18.8%
6/32 • Number of events 27
Blood and lymphatic system disorders
hemolysis
6.2%
2/32 • Number of events 2
General disorders
pain, back
18.8%
6/32 • Number of events 7
General disorders
Pain, abdomen NOS
15.6%
5/32 • Number of events 7
General disorders
Pain, head/headache
12.5%
4/32 • Number of events 4
General disorders
Pain, chest/thorax NOS
9.4%
3/32 • Number of events 3
General disorders
Pain Extremity-limb
6.2%
2/32 • Number of events 2
General disorders
Pain, chest wall
3.1%
1/32 • Number of events 1
General disorders
Pain, oral cavity
3.1%
1/32 • Number of events 1
Investigations
Creatinine, increased
21.9%
7/32 • Number of events 13
Investigations
Alt, SGPT
18.8%
6/32 • Number of events 8
Investigations
hyperglycemia
18.8%
6/32 • Number of events 9
Investigations
hypoalbuminemia
15.6%
5/32 • Number of events 7
Investigations
hypocalcemia
12.5%
4/32 • Number of events 8
Investigations
hypokalemia
12.5%
4/32 • Number of events 7
Investigations
alkaline phosphatase
9.4%
3/32 • Number of events 4
Investigations
hypomagnesemia
9.4%
3/32 • Number of events 3
Investigations
hyponatremia
9.4%
3/32 • Number of events 5
Investigations
hyperbilirubinemia
6.2%
2/32 • Number of events 2
Investigations
hyperkalemia
6.2%
2/32 • Number of events 4
Investigations
proteinuria
6.2%
2/32 • Number of events 2
Investigations
Bicarbonate, serum-low
3.1%
1/32 • Number of events 1
Investigations
Glomerular Filtration rate
3.1%
1/32 • Number of events 4
Investigations
hypophosphatemia
3.1%
1/32 • Number of events 1
Nervous system disorders
Neuropathy: sensory
21.9%
7/32 • Number of events 9
Nervous system disorders
Dizziness
15.6%
5/32 • Number of events 5
Nervous system disorders
Cognitive distrubance
3.1%
1/32 • Number of events 1
Nervous system disorders
memory impariment
3.1%
1/32 • Number of events 1
Nervous system disorders
Mood alteration - Anxeity
3.1%
1/32 • Number of events 1
Respiratory, thoracic and mediastinal disorders
Dyspnea
21.9%
7/32 • Number of events 10
Respiratory, thoracic and mediastinal disorders
pneumonitis/pulmonary infiltrates
6.2%
2/32 • Number of events 3
Respiratory, thoracic and mediastinal disorders
Cough
3.1%
1/32 • Number of events 1
Respiratory, thoracic and mediastinal disorders
Hiccoughs
3.1%
1/32 • Number of events 1
Respiratory, thoracic and mediastinal disorders
hypoxia
3.1%
1/32 • Number of events 1
Respiratory, thoracic and mediastinal disorders
pulmonary/upper respiratory
3.1%
1/32 • Number of events 1
Respiratory, thoracic and mediastinal disorders
Voice changes/dysarthria
3.1%
1/32 • Number of events 1
Skin and subcutaneous tissue disorders
Hair loss/alopecia
12.5%
4/32 • Number of events 4
Skin and subcutaneous tissue disorders
Rash: acne/acneiform
6.2%
2/32 • Number of events 2
Skin and subcutaneous tissue disorders
Rash: erythema multiforme
6.2%
2/32 • Number of events 4
Skin and subcutaneous tissue disorders
bruising (in absence of grade 3 or 4 thrombocytopenia)
3.1%
1/32 • Number of events 1
Skin and subcutaneous tissue disorders
Dry Skin
3.1%
1/32 • Number of events 1
Skin and subcutaneous tissue disorders
hypopigmentation
3.1%
1/32 • Number of events 1
Skin and subcutaneous tissue disorders
injection site reaction/extravasation changes
3.1%
1/32 • Number of events 2
Skin and subcutaneous tissue disorders
Nail Changes
3.1%
1/32 • Number of events 1
Skin and subcutaneous tissue disorders
Rash/desquamation
3.1%
1/32 • Number of events 1
Skin and subcutaneous tissue disorders
Rash: hand-foot skin reaction
3.1%
1/32 • Number of events 1
Skin and subcutaneous tissue disorders
Skin breakdown/decubitus ulcer
3.1%
1/32 • Number of events 1
Infections and infestations
Infection with unknown ANC - Bladder
3.1%
1/32 • Number of events 1
Infections and infestations
Infection with unknown ANC - Sinus
3.1%
1/32 • Number of events 1
Infections and infestations
infection with unknown ANC - Urinary tract NOS
3.1%
1/32 • Number of events 1
General disorders
hemorrhage/bleeding
6.2%
2/32 • Number of events 5
Gastrointestinal disorders
hemorrhage, GI - Varices
3.1%
1/32 • Number of events 1
Renal and urinary disorders
hemorrhage, GU - bladder
3.1%
1/32 • Number of events 1
Renal and urinary disorders
Hemorrhage, GU - Urinary NOS
3.1%
1/32 • Number of events 1
Respiratory, thoracic and mediastinal disorders
Hemorrhage, pulmonary/upper respiratory - Nose
3.1%
1/32 • Number of events 1
Musculoskeletal and connective tissue disorders
Musculoskeletal/Soft Tissue - other
6.2%
2/32 • Number of events 2
Musculoskeletal and connective tissue disorders
muscle weakness, extraocular
3.1%
1/32 • Number of events 1
Musculoskeletal and connective tissue disorders
muscle weakness, whole body/generalized
3.1%
1/32 • Number of events 1
Vascular disorders
Thrombosis/thrombus/embolism
9.4%
3/32 • Number of events 4
Vascular disorders
vascular - other
3.1%
1/32 • Number of events 1
Cardiac disorders
hypertension
9.4%
3/32 • Number of events 3
Ear and labyrinth disorders
Hearing: patients without baseline audiogram and not enrolled in a monitoring program
3.1%
1/32 • Number of events 1
Ear and labyrinth disorders
Tinnitus
3.1%
1/32 • Number of events 1
Blood and lymphatic system disorders
Edema: head and neck
3.1%
1/32 • Number of events 1
Blood and lymphatic system disorders
Edema: limb
3.1%
1/32 • Number of events 1
General disorders
growth and development- other
3.1%
1/32 • Number of events 1
Eye disorders
vision-flashing lights/floaters
3.1%
1/32 • Number of events 1
Reproductive system and breast disorders
gynecomastia
3.1%
1/32 • Number of events 1

Additional Information

Sandy Srinivas, MD

Stanford University

Phone: 650 498 6000

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place