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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Indiana University
ClinicalTrials.gov Identifier:
NCT00827372
First received: January 20, 2009
Last updated: October 15, 2014
Last verified: October 2014
  Purpose

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.


Condition Intervention Phase
Lymphedema
Drug: Pazopanib
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Supportive Care
Official Title: A Phase II Study of VEGF Inhibition in Patients With Unilateral Upper Extremity Lymphedema Following Treatment for Cancer

Resource links provided by NLM:


Further study details as provided by Indiana University:

Primary Outcome Measures:
  • Change in Volume Ipsilateral Lymphedema in Arm [ Time Frame: Baseline through Cycle 6, Day 1 ] [ Designated as safety issue: No ]
    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 [ Time Frame: First 24 hours after drug was administered ] [ Designated as safety issue: No ]

    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 [ Time Frame: Baseline, and Cycle 2, Day 1 ] [ Designated as safety issue: No ]

    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 [ Time Frame: End of Treatment ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: Baseline through Cycle 6, Day 1 ] [ Designated as safety issue: No ]

    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



Enrollment: 10
Study Start Date: January 2009
Study Completion Date: July 2010
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pazopanib Treatment
Pazopanib 800 mg orally once each day (maximum total duration of treatment = 24 weeks)
Drug: Pazopanib
Pazopanib will be administered at a starting dose of 800 mg orally once each day.
Other Name: GW786034

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00827372

Locations
United States, Indiana
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States, 46202
Sponsors and Collaborators
Indiana University
Investigators
Principal Investigator: Kathy Miller, MD IU Simon Cancer Center
  More Information

No publications provided

Responsible Party: Indiana University
ClinicalTrials.gov Identifier: NCT00827372     History of Changes
Other Study ID Numbers: 0811-15 /IUCRO-0248
Study First Received: January 20, 2009
Results First Received: September 2, 2014
Last Updated: October 15, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Lymphedema
Lymphatic Diseases
Endothelial Growth Factors
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 19, 2014