Prospective Evaluation of a Surgical Solution for Breast Cancer-Associated Lymphedema (Biobridge)

To investigate whether addition of the Biobridge scaffold to the standard surgery for vascularized lymph node transfer will improve the outcome of surgical treatment in lymphedema of the upper arm.

Study Overview

• Status: Completed
• Conditions: Lymphedema; Edema
• Intervention / Treatment: Device: Biobridge and lymph node transfer

Detailed Description

The investigators will perform lymph scans (lymphoscintigrams) before surgery and one year following surgery to determine the success of the surgery. In addition, the volume of the operated arm will be monitored by repeated measurement with a tape measure. The investigators will also track bioimpedance, a painless technique to detect fluid in the tissues. The investigators will obtain small skin biopsies and blood samples to detect the biological changes that may occur as a result of successful surgery.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

The subject must be a breast cancer survivor, at least three years beyond completion of cancer therapy, free of clinical disease, and eligible for surgical intervention.

• Ages 18 to 75 years (inclusive).
• Swelling of 1 limb that is not completely reversed by elevation or compression
• Stage II or greater lymphedema at screening, based on the International Society of Lymphology (ISL) staging system
• Completion of a full course of complete decongestive therapy (CDT), according to ISL guidelines at least 8 weeks prior to screening, including use of compression garments for at least 8 weeks without change in regimen
• Willingness to maintain a stable regimen of self-care, with consistent use of compression garments from screening through the entire study duration (through the safety follow-up visit). Self-bandaging, use of nighttime compression garments, and intermittent pneumatic compression devices are allowed, but the procedures and regimens must remain consistent from screening though the entire study duration.
• Two consecutive measurements of limb volume (LV) in the affected limb taken at least 1 day apart during the screening period must be within 10% of each other. A maximum of 3 measurements can be taken. Affected limb volume ratio >20% (affected limb compared to unaffected limb); volume measurements will be performed and volume ratio will be calculated at S1 and S2 visit.
• Evidence of abnormal bioimpedance ratio, if feasible based upon unilateral disease: L-Dex >10 units; bioimpedance performed at S1 and S1
• Willingness and ability to understand and the willingness to sign a written informed consent form document
• Willingness and ability to comply with all study procedures, including measurement of skin thickness using skin calipers.
• Participants must have NED, completed breast cancer therapy 3 years prior to enrollment.
• ECOG 0- 2

Exclusion Criteria:

• Edema arising from increased capillary filtration will be excluded.
• Inability to safely undergo general anesthesia and/or perioperative care related to vascularized lymph node transfer
• Concurrent participation in a clinical trial of any other investigational drug or therapy, regardless of indication, within 1 month before screening or 5 times the drug's half-life, whichever is longer
• Recent initiation of (≤8 weeks), or intention to initiate, CDPT or maintenance physiotherapy for lymphedema at any time during the duration of the study
• Other medical condition that could lead to acute limb edema, such as (but not limited to) acute venous thrombosis
• Other medical condition that could result in symptoms overlapping those of lymphedema in the affected limb (e.g., pain, swelling, decreased range of motion)
• History of clotting disorder (hypercoagulable state)
• Chronic (persistent) infection in the affected limb
• Any other infection (unrelated to lymphedema) within 1 month prior to screening
• Current evidence of malignancy or any high risk for breast cancer recurrence (Stage III or IV, ER/PR/HER-2 negative (triple negative) cancer , locally advanced disease, inflammatory breast cancer, > 3 positive axillary lymph nodes, extracapsular nodal extension, invasive micropapillary breast carcinoma, or if performed, patients with a high risk of recurrence based on multi-gene signatures, e.g. BRCA1, BRCA 2, Oncotype DX (high risk recurrence score) or Mammaprint (poor risk signature)
• Currently receiving chemotherapy or radiation therapy
• Life expectancy < 2 years for any reason
• Pregnancy or nursing
• Substance abuse (such as alcohol or drug abuse) within 6 months prior to screening
• Significant or chronic renal insufficiency (defined as serum creatinine > 2.5 mg/dL or an estimated glomerular filtration rate [eGFR] < 30 mL/min at screening) or requires dialytic support
• Hepatic dysfunction, defined as alanine transaminase (ALT) or aspartate transaminase (AST) levels > 3 × upper limit of the normal range (ULN) and/or bilirubin level > 2 × ULN at screening
• Absolute neutrophil count < 1500 mm3 at screening
• Hemoglobin concentration < 9 g/dL at screening
• Known sensitivity to porcine products
• Any reason (in addition to those listed above) that, in the opinion of the investigator, precludes full participation in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Biobridge and lymph node transfer; The investigators will investigate whether addition of the Biobridge scaffold to the standard surgery for vascularized lymph node transfer will improve the outcome of surgical treatment in lymphedema of the upper arm. The investigators will perform lymph scans (lymphoscintigrams) before surgery and one year following surgery to determine the success of the surgery. In addition, the volume of the operated arm will be monitored by repeated measurement with a tape measure. The investigators will also track bioimpedance, a painless technique to detect fluid in the tissues. The investigators will obtain small skin biopsies and blood samples to detect the biological changes that may occur as a result of successful surgery.

Device: Biobridge and lymph node transfer; Biobridge is surgically implanted with conventional vascularized lymph node transfer surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Limb Volume	Lymphoscintigraphy, a measure of limb volume indicative of adequate limb drainage, was conducted on the arm receiving BioBridge implantation (affected arm) and the contralateral (unaffected) arm, before surgery (baseline) and 1 year following surgical implantation of the Biobridge device. The outcome is reported as the median difference in the pre-implantation baseline value and the value 1 year after surgery for each arm.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serial Lymphoscintigraphy (LSG)	Lymphoscintigraphy, a measure of limb volume for which changes are indicative of adequate limb drainage, was conducted on the arm receiving the BioBridge implantation (baseline) and 1 year following the Biobridge implantation. The outcome is reported as the median difference in measured volume for affected arm from baseline to 1 year.	1 year
Bioimpedance Spectroscopy	Bioimpedance spectroscopy (BIS) is a non-invasive technique to measure the volume of fluid in various parts of the body, and can be used to assess the extent of lymphedema. BIS involves passing an extremely low-strength electrical current through the area and measuring how the flow of the current is slowed by the fluid in the body, and is reported as Ri in ohms, meaning the resistance of the intracellular fluid. BIS was conducted on the arm with the BioBridge implant, at baseline and 1 year after surgery. The outcome is reported as the median difference between baseline and 1 year after surgery in the arm receiving the BioBridge implant.	1 year
Caliper Skin-fold Thickness	Skin fold thickness as measured by calipers was used as a measure of fluid retention. Skin fold thickness was measured at the upper arm, forearm, and back of the hand, at baseline and at 1 year following surgical implantation of the Biobridge device. An increase in skin thickness means increased fluid retention. The outcome is reported as the median difference of skin fold thickness in millimeters (mm) for each location on the arm receiving the BioBridge implant, from baseline to 1 year.	1 year
Cutaneous Punch Biopsy of Skin	Serial changes in histopathology will be determined via a blinded assessment of serial cutaneous punch biopsies specimens.	1 year
Quality of Life for Limb Lymphoedema (LYMQOL)	Quality-of-life was assessed using the LYMQOL survey, a 5-question survey for improved function, appearance, symptoms, mood, and overall QOL. Overall QoL was reported on a 10-point scale with 10 being best, and the other assessments were for disease impact on a 4-point response scale consisting of 1 (none), 2 (a little), 3 (quite a bit), 4 (a lot), with lower values representing minimal disease (lymphedema) impact on the parameter and higher values representing a greater negative effect on the parameter. The outcome is reported as the median.	1 year

Collaborators and Investigators

• Sponsor: Stanford University
• Investigators: Principal Investigator: Stanley G Rockson, MD, Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2016
• Primary Completion (Actual): July 7, 2018
• Study Completion (Actual): October 29, 2020

Study Registration Dates

• First Submitted: April 5, 2016
• First Submitted That Met QC Criteria: April 5, 2016
• First Posted (Estimate): April 12, 2016

Study Record Updates

• Last Update Posted (Actual): October 27, 2022
• Last Update Submitted That Met QC Criteria: October 25, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: edema; lymphedema
• Additional Relevant MeSH Terms: Lymphatic Diseases; Lymphedema
• Other Study ID Numbers: IRB-37161; BRS0095 (Other Identifier: OnCore)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No