Lymphedema
Conditions
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.
Interventions
DRUGPazopanib
Pazopanib will be administered at a starting dose of 800 mg orally once each day.
Sponsors
Kathy Miller
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Volume Ipsilateral Lymphedema in Arm | Baseline through Cycle 6, Day 1 | 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
| Measure | Time frame | Description |
|---|---|---|
| Changes in Interstitial Fluid Pressure (ECF Volume) in the Arm | First 24 hours after drug was administered | 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 | Baseline, and Cycle 2, Day 1 | 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 | End of Treatment | 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) | Baseline through Cycle 6, Day 1 | 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 |
Countries
United States
Participant flow
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.
Participants by arm
| Arm | Count |
|---|---|
| Overall Study All patients who were treated | 10 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 5 |
| Overall Study | Lack of Efficacy | 3 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants |
| Age, Continuous | 56.3 Years STANDARD_DEVIATION 11.92 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 9 Participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 10 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
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).
Time frame: Baseline through Cycle 6, Day 1
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overall Study | Change in Volume Ipsilateral Lymphedema in Arm | Change from Baseline to Cycle 6, Day 1 | -372.8 mL | Standard Deviation 233.2 |
| Overall Study | Change in Volume Ipsilateral Lymphedema in Arm | Change from Baseline to Cycle 2, Day 1 | -161.0 mL | Standard Deviation 189.7 |
Comparison: 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.p-value: 0.0658t-test, 2 sided
Secondary
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
Time frame: Baseline, and Cycle 2, Day 1
Population: 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 | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Overall Study | Change in Impedance or ECF Volume in the Arm | Impedence Baseline 1 | 1.39 ratio | Standard Deviation 0.34 |
| Overall Study | Change in Impedance or ECF Volume in the Arm | Impedence Baseline 2 | 1.43 ratio | Standard Deviation 0.31 |
| Overall Study | Change in Impedance or ECF Volume in the Arm | Impedence Cycle 2, Day 1 | 1.46 ratio | Standard Deviation 0.25 |
Comparison: A Paired T-Test was used for the difference in the impedance ratio from the second baseline to cycle 2, day 1p-value: 0.0143t-test, 2 sided
Secondary
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)
Time frame: First 24 hours after drug was administered
Population: All patients with non-missing results at both baseline and at 24 hours.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Overall Study | Changes in Interstitial Fluid Pressure (ECF Volume) in the Arm | -0.76 mm Hg | Standard Deviation 0.28 |
Comparison: A Paired T-Test was used to compare the IFP affected at first versus affected at last reading.p-value: 0.0061t-test, 2 sided
Secondary
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
Time frame: Baseline through Cycle 6, Day 1
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overall Study | Clinical Benefit as Assessed by Quality of Life Questionnaire (FACT-B+4 Lymphedema Questions) | Cycle 1, Day 1 Physical Well Being | 25.3 Units on a scale | Standard Deviation 2.8 |
| Overall Study | Clinical Benefit as Assessed by Quality of Life Questionnaire (FACT-B+4 Lymphedema Questions) | Cycle 1, Day 1 Social Well Being | 24.9 Units on a scale | Standard Deviation 2.1 |
| Overall Study | Clinical Benefit as Assessed by Quality of Life Questionnaire (FACT-B+4 Lymphedema Questions) | Cylce 1, Day 1 Functional Well Being | 22.9 Units on a scale | Standard Deviation 3.9 |
| Overall Study | Clinical Benefit as Assessed by Quality of Life Questionnaire (FACT-B+4 Lymphedema Questions) | Cylce 1, Day 1 Emotional Well Being | 21.2 Units on a scale | Standard Deviation 2.5 |
| Overall Study | Clinical Benefit as Assessed by Quality of Life Questionnaire (FACT-B+4 Lymphedema Questions) | Cycle 1, Day 1 Additional Concerns | 25.2 Units on a scale | Standard Deviation 5.5 |
| Overall Study | Clinical Benefit as Assessed by Quality of Life Questionnaire (FACT-B+4 Lymphedema Questions) | Cycle 1, Day 1 FACT-B+4 Score | 119.5 Units on a scale | Standard Deviation 11.5 |
| Overall Study | Clinical Benefit as Assessed by Quality of Life Questionnaire (FACT-B+4 Lymphedema Questions) | Cycle 1, Day 1 Trial Outcome Index | 73.4 Units on a scale | Standard Deviation 9.2 |
| Overall Study | Clinical Benefit as Assessed by Quality of Life Questionnaire (FACT-B+4 Lymphedema Questions) | Cycle 1, Day 1 FACT G Score | 94.3 Units on a scale | Standard Deviation 7.6 |
| Overall Study | Clinical Benefit as Assessed by Quality of Life Questionnaire (FACT-B+4 Lymphedema Questions) | Cycle 1, Day 1 FACT B Score | 119.5 Units on a scale | Standard Deviation 11.5 |
| Overall Study | Clinical Benefit as Assessed by Quality of Life Questionnaire (FACT-B+4 Lymphedema Questions) | Cycle 2, Day 1 Physical Well Being | 22.0 Units on a scale | Standard Deviation 3.8 |
| Overall Study | Clinical Benefit as Assessed by Quality of Life Questionnaire (FACT-B+4 Lymphedema Questions) | Cycle 2, Day 1 Social Well Being | 25.8 Units on a scale | Standard Deviation 2.1 |
| Overall Study | Clinical Benefit as Assessed by Quality of Life Questionnaire (FACT-B+4 Lymphedema Questions) | Cycle 2, Day 1 Functional Well Being | 21.1 Units on a scale | Standard Deviation 4.5 |
| Overall Study | Clinical Benefit as Assessed by Quality of Life Questionnaire (FACT-B+4 Lymphedema Questions) | Cycle 2, Day 1 Emotional Well Being | 20.8 Units on a scale | Standard Deviation 3.4 |
| Overall Study | Clinical Benefit as Assessed by Quality of Life Questionnaire (FACT-B+4 Lymphedema Questions) | Cycle 2, Day 1 Additional Concerns | 29.8 Units on a scale | Standard Deviation 3.7 |
| Overall Study | Clinical Benefit as Assessed by Quality of Life Questionnaire (FACT-B+4 Lymphedema Questions) | Cycle 2, Day 1 FACT-B+4 Score | 119.6 Units on a scale | Standard Deviation 11.5 |
| Overall Study | Clinical Benefit as Assessed by Quality of Life Questionnaire (FACT-B+4 Lymphedema Questions) | Cycle 2, Day 1 Trial Outcome Index | 73.0 Units on a scale | Standard Deviation 9.1 |
| Overall Study | Clinical Benefit as Assessed by Quality of Life Questionnaire (FACT-B+4 Lymphedema Questions) | Cycle 2, Day 1 FACT G Score | 89.8 Units on a scale | Standard Deviation 9.2 |
| Overall Study | Clinical Benefit as Assessed by Quality of Life Questionnaire (FACT-B+4 Lymphedema Questions) | Cycle 2, Day 1 FACT B Score | 119.6 Units on a scale | Standard Deviation 11.5 |
| Overall Study | Clinical Benefit as Assessed by Quality of Life Questionnaire (FACT-B+4 Lymphedema Questions) | Cycle 6, Day 1 Physical Well Being | 24.5 Units on a scale | Standard Deviation 0.7 |
| Overall Study | Clinical Benefit as Assessed by Quality of Life Questionnaire (FACT-B+4 Lymphedema Questions) | Cycle 6, Day 1 Social Well Being | 27.4 Units on a scale | Standard Deviation 0.8 |
| Overall Study | Clinical Benefit as Assessed by Quality of Life Questionnaire (FACT-B+4 Lymphedema Questions) | Cylce 6, Day 1 Functional Well Being | 25.5 Units on a scale | Standard Deviation 3.5 |
| Overall Study | Clinical Benefit as Assessed by Quality of Life Questionnaire (FACT-B+4 Lymphedema Questions) | Cylce 6, Day 1 Emotional Well Being | 23.0 Units on a scale | Standard Deviation 1.4 |
| Overall Study | Clinical Benefit as Assessed by Quality of Life Questionnaire (FACT-B+4 Lymphedema Questions) | Cycle 6, Day 1 Additional Concerns | 30.9 Units on a scale | Standard Deviation 2.4 |
| Overall Study | Clinical Benefit as Assessed by Quality of Life Questionnaire (FACT-B+4 Lymphedema Questions) | Cycle 6, Day 1 FACT-B+4 Score | 140.9 Units on a scale | Standard Deviation 20.9 |
| Overall Study | Clinical Benefit as Assessed by Quality of Life Questionnaire (FACT-B+4 Lymphedema Questions) | Cycle 6, Day 1 Trial Outcome Index | 80.9 Units on a scale | Standard Deviation 5.2 |
| Overall Study | Clinical Benefit as Assessed by Quality of Life Questionnaire (FACT-B+4 Lymphedema Questions) | Cycle 6, Day 1 FACT G Score | 100.4 Units on a scale | Standard Deviation 5.1 |
| Overall Study | Clinical Benefit as Assessed by Quality of Life Questionnaire (FACT-B+4 Lymphedema Questions) | Cycle 6, Day 1 FACT B Score | 131.4 Units on a scale | Standard Deviation 7.5 |
Secondary
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').
Time frame: End of Treatment
Population: All treated patients
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Overall Study | Number of Patients With Trt Related Grade 2+ AEs | Patients with Trt Related Grade 2+ AEs | 9 participants |
| Overall Study | Number of Patients With Trt Related Grade 2+ AEs | Patients with Trt Related Grade 2+ AEs (special) | 7 participants |