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A Study of Vascular Endothelial Growth Factor (VEGF) Inhibition in Patients With Unilateral Upper Extremity Lymphedema Following Treatment for Cancer

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ClinicalTrials.gov Identifier: NCT00827372
Recruitment Status : Completed
First Posted : January 22, 2009
Results First Posted : October 16, 2014
Last Update Posted : October 16, 2014
Sponsor:
Information provided by (Responsible Party):
Indiana University

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Supportive Care
Condition Lymphedema
Intervention Drug: Pazopanib
Enrollment 10
Recruitment Details This study was to enroll 14-15 patients. Due to toxicity and enough patients met the definition of response , this study was halted early, leading to a smaller number of subjects analyzed. There were 10 patients at baseline, 7 patients at Cycle 2, Day 1 and 2 patients who completed the 6 cycles of planned treatment.
Pre-assignment Details  
Arm/Group Title Overall Study
Hide Arm/Group Description All patients who were treated
Period Title: Overall Study
Started 10
Completed 2
Not Completed 8
Reason Not Completed
Adverse Event             5
Lack of Efficacy             3
Arm/Group Title Overall Study
Hide Arm/Group Description All patients who were treated
Overall Number of Baseline Participants 10
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants
<=18 years
0
   0.0%
Between 18 and 65 years
9
  90.0%
>=65 years
1
  10.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 10 participants
56.3  (11.92)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants
Female
10
 100.0%
Male
0
   0.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants
Hispanic or Latino
0
   0.0%
Not Hispanic or Latino
10
 100.0%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
1
  10.0%
White
9
  90.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
1.Primary Outcome
Title Change in Volume Ipsilateral Lymphedema in Arm
Hide Description The primary endpoint will be change in excess arm volume (affected arm volume minus unaffected arm volume) compared to baseline. This will be done at Cycle 2 (29 days) and Cycle 6 (174 days).
Time Frame Baseline through Cycle 6, Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
All patients with non-missing results. There were 10 patients at baseline, 7 patients at Cycle 2, Day 1, and 2 patients who completed the 6 cycles of treatment.
Arm/Group Title Overall Study
Hide Arm/Group Description:
All patients who were treated
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: mL
Change from Baseline to Cycle 2, Day 1 -161.0  (189.7)
Change from Baseline to Cycle 6, Day 1 -372.8  (233.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Overall Study
Comments With a sample size of 14 evaluable subjects, we will have 80% power to detect a change in excess arm volume of .8 standard deviations using a two-sided paired t-test. We will have 90% power to detect a difference of .9 standard deviations. A Paired T-Test was used to test the difference in arm volume from the second baseline measurement to Cycle 2 only.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0658
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
2.Secondary Outcome
Title Changes in Interstitial Fluid Pressure (ECF Volume) in the Arm
Hide Description

Interstitial fluid pressure was reported at 24 hours. This is the difference in the last-first reading, affected arm.

To assess the degree of improvement in arm edema as measured by changes in interstitial fluid pressure (ECF volume using an automated device lymphometer)

Time Frame First 24 hours after drug was administered
Hide Outcome Measure Data
Hide Analysis Population Description
All patients with non-missing results at both baseline and at 24 hours.
Arm/Group Title Overall
Hide Arm/Group Description:
All patients who were treated
Overall Number of Participants Analyzed 7
Mean (Standard Deviation)
Unit of Measure: mm Hg
-0.76  (0.28)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Overall
Comments A Paired T-Test was used to compare the IFP affected at first versus affected at last reading.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0061
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
3.Secondary Outcome
Title Change in Impedance or ECF Volume in the Arm
Hide Description

Arm impedance was reported at two baseline readings and for Cycle 2, Day 1.

To assess the degree of improvement in arm edema as measured by changes in arm impedance (ECF volume using an automated device lymphometer). Data reported is the ratio of the impedance in the affected versus unaffected arm

Time Frame Baseline, and Cycle 2, Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
All patients with non-missing results. This includes 8 patients at the first baseline, 10 patients at the second baseline, and 7 patients at Cycle 2, Day 1.
Arm/Group Title Overall
Hide Arm/Group Description:
All patients who were treated
Overall Number of Participants Analyzed 10
Median (Standard Deviation)
Unit of Measure: ratio
Impedence Baseline 1 1.39  (0.34)
Impedence Baseline 2 1.43  (0.31)
Impedence Cycle 2, Day 1 1.46  (0.25)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Overall
Comments A Paired T-Test was used for the difference in the impedance ratio from the second baseline to cycle 2, day 1
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0143
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
4.Secondary Outcome
Title Number of Patients With Trt Related Grade 2+ AEs
Hide Description This is the number of patients who had greater than or equal to Grade 2 Adverse Events related to treatment. This also includes the number of patients who had treatment related Grade 2 or greater Adverse Events that lasted more than 2 weeks (14 days) and excluded events of hypertension (labeled as 'special').
Time Frame End of Treatment
Hide Outcome Measure Data
Hide Analysis Population Description
All treated patients
Arm/Group Title Overall
Hide Arm/Group Description:
All patients who were treated
Overall Number of Participants Analyzed 10
Measure Type: Number
Unit of Measure: participants
Patients with Trt Related Grade 2+ AEs 9
Patients with Trt Related Grade 2+ AEs (special) 7
5.Secondary Outcome
Title Clinical Benefit as Assessed by Quality of Life Questionnaire (FACT-B+4 Lymphedema Questions)
Hide Description

The quality of life questionnaire (FACT-B+4 lymphedema questions) was given at various timepoints during the study. The values for the subscales are given for baseline, Cycle 1:Day 1, Cycle 2:Day 1, and Cycle 6:Day 1.

Physical Well-Being (PWB; sum of 7 items, point range 0-28) Social /Family Well-Being (SWB, sum of 7-items, point range 0-28) Emotional Well-Being (EWB; sum of 6-items, point range 0-24) Functional Well-Being (FWB; sum of 7-items, point range 0-28) Additional Concerns (BCS; sum of 9-items, point range 0-36) Arm subscale (AS; sum of 5-items, point range 0-20) -- This was not collected in Cycle 1 or 2.

Fact-B+4 score=Sum of PWB, SWB, EWB, FWB, BCS, AS, point range 0-164 Trial Outcome Index=Sum of PWB, FWB, BCS, point range 0-92 Fact-G score=sum of PWB, SWB, EWB, FWB, point range 0-108 Fact-B score=sum of PWB, SWB, EWB, FWB, BCS, point range 0-144 Note: The higher the score, the better the outcome

Time Frame Baseline through Cycle 6, Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
All patients with non-missing results. There were 10 patients at baseline/Cycle 1, Day 1, 7 patients at Cycle 2, Day 1, and 2 patients who completed the 6 cycles of treatment.
Arm/Group Title Overall
Hide Arm/Group Description:
All patients who were treated
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Cycle 1, Day 1 Physical Well Being 25.3  (2.8)
Cycle 1, Day 1 Social Well Being 24.9  (2.1)
Cylce 1, Day 1 Functional Well Being 22.9  (3.9)
Cylce 1, Day 1 Emotional Well Being 21.2  (2.5)
Cycle 1, Day 1 Additional Concerns 25.2  (5.5)
Cycle 1, Day 1 FACT-B+4 Score 119.5  (11.5)
Cycle 1, Day 1 Trial Outcome Index 73.4  (9.2)
Cycle 1, Day 1 FACT G Score 94.3  (7.6)
Cycle 1, Day 1 FACT B Score 119.5  (11.5)
Cycle 2, Day 1 Physical Well Being 22.0  (3.8)
Cycle 2, Day 1 Social Well Being 25.8  (2.1)
Cycle 2, Day 1 Functional Well Being 21.1  (4.5)
Cycle 2, Day 1 Emotional Well Being 20.8  (3.4)
Cycle 2, Day 1 Additional Concerns 29.8  (3.7)
Cycle 2, Day 1 FACT-B+4 Score 119.6  (11.5)
Cycle 2, Day 1 Trial Outcome Index 73.0  (9.1)
Cycle 2, Day 1 FACT G Score 89.8  (9.2)
Cycle 2, Day 1 FACT B Score 119.6  (11.5)
Cycle 6, Day 1 Physical Well Being 24.5  (0.7)
Cycle 6, Day 1 Social Well Being 27.4  (0.8)
Cylce 6, Day 1 Functional Well Being 25.5  (3.5)
Cylce 6, Day 1 Emotional Well Being 23.0  (1.4)
Cycle 6, Day 1 Additional Concerns 30.9  (2.4)
Cycle 6, Day 1 FACT-B+4 Score 140.9  (20.9)
Cycle 6, Day 1 Trial Outcome Index 80.9  (5.2)
Cycle 6, Day 1 FACT G Score 100.4  (5.1)
Cycle 6, Day 1 FACT B Score 131.4  (7.5)
Time Frame Adverse Events are reported from the beginning of study until the end of the study, up to 28 weeks.
Adverse Event Reporting Description There were no serious adverse events entered in this trial.
 
Arm/Group Title Overall
Hide Arm/Group Description All patients who were treated
All-Cause Mortality
Overall
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Overall
Affected / at Risk (%) # Events
Total   0/10 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Overall
Affected / at Risk (%) # Events
Total   10/10 (100.00%)    
Eye disorders   
VISION-BLURRED VISION * 1  1/10 (10.00%)  1
Gastrointestinal disorders   
MUCOSITIS/STOMATITIS (CLINICAL EXAM) - ORAL CAVITY * 1  5/10 (50.00%)  5
CONSTIPATION * 1  2/10 (20.00%)  2
DIARRHEA * 1  6/10 (60.00%)  6
FLATULENCE * 1  1/10 (10.00%)  1
HEARTBURN/DYSPEPSIA * 1  4/10 (40.00%)  4
NAUSEA * 1  4/10 (40.00%)  4
PAIN - ABDOMEN NOS * 1  1/10 (10.00%)  1
PAIN - ORAL-GUMS * 1  1/10 (10.00%)  1
TASTE ALTERATION (DYSGEUSIA) * 1  6/10 (60.00%)  6
VOMITING * 1  2/10 (20.00%)  2
General disorders   
FATIGUE (ASTHENIA, LETHARGY, MALAISE) * 1  8/10 (80.00%)  8
FEVER (IN THE ABSENCE OF NEUTROPENIA, WHERE NEUTROPENIA IS DEFINED AS ANC <1.0 X 10E9/L) * 1  2/10 (20.00%)  2
SWEATING (DIAPHORESIS) * 1  1/10 (10.00%)  1
Investigations   
ALKALINE PHOSPHATASE * 1  1/10 (10.00%)  1
Metabolism and nutrition disorders   
ANOREXIA * 1  7/10 (70.00%)  7
Musculoskeletal and connective tissue disorders   
INFECTION WITH NORMAL ANC OR GRADE 1 OR 2 NEUTROPHILS - NECK NOS * 1  1/10 (10.00%)  1
INFECTION WITH NORMAL ANC OR GRADE 1 OR 2 NEUTROPHILS - SKIN (CELLULITIS) * 1  1/10 (10.00%)  1
PAIN - EXTREMITY-LIMB * 1  2/10 (20.00%)  2
PAIN - JOINT * 1  3/10 (30.00%)  3
PAIN - NECK * 1  1/10 (10.00%)  1
PAIN - BACK * 1  1/10 (10.00%)  1
Nervous system disorders   
NEUROPATHY: SENSORY * 1  2/10 (20.00%)  2
PAIN - HEAD/HEADACHE * 1  1/10 (10.00%)  1
PAIN - NEURALGIA/PERIPHERAL NERVE * 1  1/10 (10.00%)  1
Psychiatric disorders   
INSOMNIA * 1  4/10 (40.00%)  4
MOOD ALTERATION - DEPRESSION * 1  3/10 (30.00%)  3
Respiratory, thoracic and mediastinal disorders   
COUGH * 1  3/10 (30.00%)  3
DYSPNEA (SHORTNESS OF BREATH) * 1  2/10 (20.00%)  2
INFECTION WITH NORMAL ANC OR GRADE 1 OR 2 NEUTROPHILS - SINUS * 1  1/10 (10.00%)  1
Skin and subcutaneous tissue disorders   
DERMATOLOGY/SKIN - OTHER (SPECIFY, __) * 1  1/10 (10.00%)  1
HAIR LOSS/ALOPECIA (SCALP OR BODY) * 1  7/10 (70.00%)  7
HYPOPIGMENTATION * 1  2/10 (20.00%)  2
PRURITUS/ITCHING * 1  3/10 (30.00%)  3
RASH/DESQUAMATION * 1  1/10 (10.00%)  1
RASH: ACNE/ACNEIFORM * 1  3/10 (30.00%)  3
RASH: ERYTHEMA MULTIFORME (E.G., STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS) * 1  1/10 (10.00%)  1
Vascular disorders   
HOT FLASHES/FLUSHES * 1  1/10 (10.00%)  1
HYPERTENSION * 1  1/10 (10.00%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA version 9
This study was to enroll 14-15 patients. Due to toxicity and enough patients met the definition of response, enrollment to this study was halted early, leading to a smaller number of subjects analyzed.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Kathy Miller, MD
Organization: IndianaU
Phone: 317-944-0920
Responsible Party: Indiana University
ClinicalTrials.gov Identifier: NCT00827372     History of Changes
Other Study ID Numbers: 0811-15 /IUCRO-0248
First Submitted: January 20, 2009
First Posted: January 22, 2009
Results First Submitted: September 2, 2014
Results First Posted: October 16, 2014
Last Update Posted: October 16, 2014