Back to resultsA Study of Vascular Endothelial Growth Factor (VEGF) Inhibition in Patients With Unilateral Upper Extremity Lymphedema Following Treatment for Cancer
Primary Purpose
Lymphedema
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Pazopanib
Sponsored by
About this trial
This is an interventional supportive care trial for Lymphedema
Eligibility Criteria
Inclusion Criteria:
- Have unilateral lymphedema of the ipsilateral arm attributed to prior surgical treatment or radiation therapy for cancer that is severe enough to warrant therapy in the opinion of the patient and treating physician.
- All patients must have greater than a 3 cm total difference in arm circumference between the affected and unaffected arm measured at five defined points (see protocol).
- Be at least 18 years of age
- Have adequate organ function as specified in the protocol.
- Agree to use effective contraceptive methods during the course of the study if the patient has child-producing potential
- Have an ECOG performance status of 0 or 1
Exclusion Criteria:
- Pregnant, lactating, or unwilling to use appropriate birth control
- Active infection
- Patients may not have clinically significant cardiovascular disease including myocardial infarction within 6 months prior to initiation of therapy, unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, grade II or greater peripheral vascular disease, uncontrolled hypertension defined as SBP>160 or DBP>90. Patients may not have any prior history of cerebrovascular disease including TIA or stroke.
- Locally recurrent or metastatic disease
- Concurrent therapeutic anticoagulation or any history of DVT or PE.
- Major surgery within 4 weeks of starting protocol therapy (non-operative biopsy or placement of a vascular access device is not considered major surgery)
- Radiation therapy or chemotherapy within the past 6 weeks or currently undergoing radiation therapy or chemotherapy (Concurrent adjuvant hormonal therapy is allowed.)
- Altered the physical therapy regimen within the past month
- Indwelling venous device in the ipsilateral arm
- Bilateral lymphedema
- Concomitant requirement for medication classified as substrates for the CYP450 enzymes and listed as prohibited in the protocol.
Sites / Locations
- Indiana University Melvin and Bren Simon Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Pazopanib Treatment
Arm Description
Pazopanib 800 mg orally once each day (maximum total duration of treatment = 24 weeks)
Outcomes
Primary Outcome Measures
Change in Volume Ipsilateral Lymphedema in Arm
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).
Secondary Outcome Measures
Changes in Interstitial Fluid Pressure (ECF Volume) in the Arm
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)
Change in Impedance or ECF Volume in the Arm
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
Number of Patients With Trt Related Grade 2+ AEs
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').
Clinical Benefit as Assessed by Quality of Life Questionnaire (FACT-B+4 Lymphedema Questions)
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00827372
Brief Title
A Study of Vascular Endothelial Growth Factor (VEGF) Inhibition in Patients With Unilateral Upper Extremity Lymphedema Following Treatment for Cancer
Official Title
A Phase II Study of VEGF Inhibition in Patients With Unilateral Upper Extremity Lymphedema Following Treatment for Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Completed
Study Start Date
January 2009 (undefined)
Primary Completion Date
July 2010 (Actual)
Study Completion Date
July 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Kathy Miller
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The major purpose of this study is to determine if a new drug called pazopanib decreases lymphedema in subjects previously treated for cancer. Lymphedema, or swelling of the arm, is a result of damage to the lymphatic vessels in the arm during surgery and/or radiation. The damaged vessels can not adequately drain fluid from the arm, resulting in increased pressure and swelling. Pazopanib has not previously been studied as a treatment for lymphedema.
Detailed Description
Pazopanib inhibits the growth of blood vessels in tumors by inhibiting a protein called vascular endothelial growth factor (commonly called VEGF). Pazopanib is not currently approved by the US Food and Drug Administration (FDA) and therefore considered an experimental medication.
High levels of VEGF cause blood vessels to leak fluid, increasing the pressure in tumors similar to the increased pressure in lymphedema. Previous studies have found that treatment with pazopanib decreases the fluid pressure in tumors. That is why we think pazopanib might be an effective treatment for lymphedema.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphedema
7. Study Design
Primary Purpose
Supportive Care
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Pazopanib Treatment
Arm Type
Experimental
Arm Description
Pazopanib 800 mg orally once each day (maximum total duration of treatment = 24 weeks)
Intervention Type
Drug
Intervention Name(s)
Pazopanib
Other Intervention Name(s)
GW786034
Intervention Description
Pazopanib will be administered at a starting dose of 800 mg orally once each day.
Primary Outcome Measure Information:
Title
Change in Volume Ipsilateral Lymphedema in Arm
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
Secondary Outcome Measure Information:
Title
Changes in Interstitial Fluid Pressure (ECF Volume) in the Arm
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
Title
Change in Impedance or ECF Volume in the Arm
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
Title
Number of Patients With Trt Related Grade 2+ AEs
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
Title
Clinical Benefit as Assessed by Quality of Life Questionnaire (FACT-B+4 Lymphedema Questions)
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Have unilateral lymphedema of the ipsilateral arm attributed to prior surgical treatment or radiation therapy for cancer that is severe enough to warrant therapy in the opinion of the patient and treating physician.
All patients must have greater than a 3 cm total difference in arm circumference between the affected and unaffected arm measured at five defined points (see protocol).
Be at least 18 years of age
Have adequate organ function as specified in the protocol.
Agree to use effective contraceptive methods during the course of the study if the patient has child-producing potential
Have an ECOG performance status of 0 or 1
Exclusion Criteria:
Pregnant, lactating, or unwilling to use appropriate birth control
Active infection
Patients may not have clinically significant cardiovascular disease including myocardial infarction within 6 months prior to initiation of therapy, unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, grade II or greater peripheral vascular disease, uncontrolled hypertension defined as SBP>160 or DBP>90. Patients may not have any prior history of cerebrovascular disease including TIA or stroke.
Locally recurrent or metastatic disease
Concurrent therapeutic anticoagulation or any history of DVT or PE.
Major surgery within 4 weeks of starting protocol therapy (non-operative biopsy or placement of a vascular access device is not considered major surgery)
Radiation therapy or chemotherapy within the past 6 weeks or currently undergoing radiation therapy or chemotherapy (Concurrent adjuvant hormonal therapy is allowed.)
Altered the physical therapy regimen within the past month
Indwelling venous device in the ipsilateral arm
Bilateral lymphedema
Concomitant requirement for medication classified as substrates for the CYP450 enzymes and listed as prohibited in the protocol.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kathy Miller, MD
Organizational Affiliation
IU Simon Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Indiana University Melvin and Bren Simon Cancer Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Study of Vascular Endothelial Growth Factor (VEGF) Inhibition in Patients With Unilateral Upper Extremity Lymphedema Following Treatment for Cancer
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