A Pilot Study of VEGF Inhibition in Patients With Lymphedema Following Breast Cancer Treatment

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Indiana University ( Indiana University School of Medicine )
ClinicalTrials.gov Identifier:
NCT00393497
First received: October 26, 2006
Last updated: March 30, 2012
Last verified: September 2011
  Purpose

The purpose of this study is to evaluate the effectiveness of bevacizumab in women with lymphedema as a result of previous treatment for breast cancer.


Condition Intervention Phase
Breast Cancer
Lymphedema
Drug: bevacizumab
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of VEGF Inhibition in Patients With Lymphedema Following Breast Cancer Treatment

Resource links provided by NLM:


Further study details as provided by Indiana University:

Primary Outcome Measures:
  • Arm Volume [ Time Frame: baseline, Day 1, Day 22, q 6wks, termination ] [ Designated as safety issue: No ]
  • The affected and unaffected arm measured at five defined points: [ Time Frame: baseline, Day 1, Day 22, q 6wks, termination ] [ Designated as safety issue: No ]
  • each hand just distal to the thumb [ Time Frame: baseline, Day 1, Day 22, q 6wks, termination ] [ Designated as safety issue: No ]
  • each wrist at its narrowest point [ Time Frame: baseline, Day 1, Day 22, q 6wks, termination ] [ Designated as safety issue: No ]
  • each arm 30 cm proximal to the tip of the middle finger [ Time Frame: baseline, Day 1, Day 22, q 6wks, termination ] [ Designated as safety issue: No ]
  • each arm 40 cm proximal to the tip of the middle finger [ Time Frame: baseline, Day 1, Day 22, q 6wks, termination ] [ Designated as safety issue: No ]
  • each arm 50 cm proximal to the tip of the middle finger (if possible before the axilla is reached.) [ Time Frame: baseline, Day 1, Day 22, q 6wks, termination ] [ Designated as safety issue: No ]
  • The volume of each arm will be calculated from these measurements using the Casley Smith method29. Treatment will be considered efficacious if there is a greater than or equal to 25% decrease in excess arm volume (affected arm volume minus unaffected arm [ Time Frame: baseline, Day 1, Day 22, q 6wks, termination ] [ Designated as safety issue: No ]
  • Patients will initially be treated for 42 days (6 weeks). [ Time Frame: Day 1-42 ] [ Designated as safety issue: No ]

Enrollment: 11
Study Start Date: April 2007
Study Completion Date: January 2011
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: bevacizumab
    Bevacizumab 15 mg/kg IV every 21 days
Detailed Description:

The primary objective of this study is:

• To assess the degree of improvement in arm edema as measured by changes in arm volume in patients with ipsilateral lymphedema

The secondary objectives of this study are:

  • To assess the degree of improvement in arm edema as measured by changes in arm interstitial fluid pressure (IFP)
  • To assess the degree of improvement in arm edema as measured by changes in extracellular fluid (ECF) volume based on bioelectrical impedance analysis (BIA) by lymphometer
  • To assess the safety and tolerability of VEGF inhibition in this patient population
  • To assess the clinical benefit in patients with ipsilateral lymphedema treated with vascular endothelial growth factor (VEGF) inhibition by evaluating patient responses to a quality of life questionnaire (FACT-B+4 lymphedema questions)
  • To determine the impact of VEGF inhibition on circulating VEGF levels in patients with lymphedema
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Have unilateral lymphedema of the ipsilateral arm attributed to prior surgical treatment or radiation therapy for breast cancer that is severe enough to warrant therapy in the opinion of the subject and treating physician.
  2. All subjects must have greater than a 3 cm total difference in arm circumference between the affected and unaffected arm measured at five defined points:

    • each hand just distal to the thumb
    • each wrist at its narrowest point
    • each arm 30 cm proximal to the tip of the middle finger
    • each arm 40 cm proximal to the tip of the middle finger
    • each arm 50 cm proximal to the tip of the middle finger (if possible before the axilla is reached.)
  3. Be at least 18 years of age
  4. Have adequate organ function as specified below:

    • AST and ALT less than or equal to 2.0 times ULN
    • Total bilirubin less than or equal to 1.5 mg/dL
    • Serum creatinine less than or equal to 1.5 mg/dL
    • Urine protein:creatinine ratio < 1.0*
    • LVEF > institutional limits of normal by MUGA or ECHO
    • PT INR < 1.5; PTT < 1.5 x normal
    • Absolute neutrophil count greater than or equal to 1000/mm3
    • Platelets greater than or equal to 100,000/mm3
  5. Agree to use effective contraceptive methods during the course of the study if the subject has child-producing potential
  6. Have an ECOG performance status of 0 or 1

Exclusion Criteria:

  1. Subjects must not be pregnant, lactating, or refuse to use appropriate birth control
  2. Subjects must not have an active infection requiring parenteral or oral antibiotics
  3. Subjects must not have clinically significant cardiovascular or cerebrovascular disease, including:

    Any history of:

    • Cerebrovascular disease including TIA, stroke or subarachnoid hemorrhage
    • Ischemic bowel
    • Hypertensive crisis or hypertensive encephalopathy Within the last 12 months
    • Myocardial infarction
    • Unstable angina
    • New York Heart Association (NYHA) grade II or greater congestive heart failure
    • Grade II or greater peripheral vascular disease
    • DVT or PE Active at study entry
    • Uncontrolled hypertension defined as SBP > 150 or DBP > 100
    • Uncontrolled or clinically significant arrhythmia.
  4. Subjects may not have locally recurrent or metastatic disease
  5. Subjects may not require concurrent therapeutic anticoagulation. (NOTE: Prophylactic doses of coumadin to maintain patency of a vascular access device is allowed). In addition, subjects with a bleeding diathesis are excluded.
  6. Subjects may not have had major surgery within 4 weeks of starting protocol therapy (NOTE: Placement of a vascular access device is not considered major surgery)
  7. Subjects may not have received radiation therapy, chemotherapy or trastuzumab within the past 6 weeks (NOTE: Concurrent adjuvant hormonal therapy is allowed.)
  8. Subjects may not have altered the physical therapy regimen for lymphedema within the past month
  9. Subjects may not have an indwelling venous device in the ipsilateral arm
  10. Subjects may not have bilateral lymphedema
  11. Subjects may not have a non-healing wound, ulcer or bone fracture.
  12. Subjects may not have a known hypersensitivity to any component of Bevacizumab
  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: NCT00393497

Locations
United States, Indiana
Indiana University Cancer Center
Indianapolis, Indiana, United States, 46202
Sponsors and Collaborators
Indiana University School of Medicine
Investigators
Principal Investigator: Kathy Miller, MD Indiana University
  More Information

Additional Information:
No publications provided

Responsible Party: Indiana University ( Indiana University School of Medicine )
ClinicalTrials.gov Identifier: NCT00393497     History of Changes
Other Study ID Numbers: 0606-24, IUCRO-0162
Study First Received: October 26, 2006
Last Updated: March 30, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Indiana University:
Breast Cancer
lymphedema

Additional relevant MeSH terms:
Breast Neoplasms
Lymphedema
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Lymphatic Diseases
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 18, 2014