LymphBridge: Surgical Evaluation for Breast Cancer-Associated Lymphedema (BioBridge)

Inclusion Criteria:

The subject must be a breast cancer survivor, at least 3 years beyond completion of cancer therapy, free of clinical disease, and eligible for surgical intervention. Participants who are not able to safely undergo general anesthesia and/or perioperative care for VLNT are excluded.

• Ages 18 to 75 years (inclusive)

• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2

• Life expectancy > 2 years

• Acquired (secondary) upper limb lymphedema secondary to breast cancer treatment

• The participant must be eligible for surgical intervention

• Swelling of 1 limb that is not completely reversed by elevation or compression

• Stage I-II lymphedema at screening, based on the International Society of Lymphology (ISL) staging system

• Participants must have no evidence of disease (NED), have completed breast cancertherapy 3 years prior to enrollment; use of endocrine therapy is allowed.

• Completion of a full course of complete decongestive therapy (CDT), according to ISLguidelines at least 12 weeks prior to screening, including use of compressiongarments for at least 12 weeks without change in regimen

• Willingness to comply with recommended regimen of self care, with consistent use ofcompression garments from screening through the entire study duration (through thesafety follow up visit), excluding the first 3 weeks postoperatively where patientsare required to not wear compression. Self bandaging, use of nighttime compressiongarments, and intermittent pneumatic compression devices are allowed, but theprocedures and regimens are expected to remain consistent from screening though theentire study duration.

• Consistent use of an appropriately sized compression garment for daytime use.

• Limb volume (LV) in the affected limb and unaffected limb must be at least 10% ofeach other.

• Evidence of abnormal bioimpedance ratio, if feasible, based upon unilateral disease:L Dex > 10 units.

• Willingness and ability to comply with all study procedures, including measurementof skin biopsy, and preoperative and postoperative imaging studies.

• Willingness and ability to understand, and to sign a written informed consent formdocument

Exclusion Criteria:

• Edema arising from increased capillary filtration will be excluded (venousincompetence).

• Inability to safely undergo general anesthesia and/or perioperative care related tovascularized lymph node transfer

• Concurrent participation in a clinical trial of any other investigational drug ortherapy, regardless of indication, within 1 month before screening or 5 times thedrug's half life, whichever is longer

• Recent initiation (≤ 12 weeks) of CDPT for lymphedema

• Other medical condition that could lead to acute limb edema, such as (but notlimited to) acute venous thrombosis or heart failure

• Other medical condition that could result in symptoms overlapping those oflymphedema in the affected limb (eg, pain, swelling, decreased range of motion)

• History of clotting disorder (hypercoagulable state)

• Chronic (persistent) infection in the affected limb

• Infection of the lymphedema limb within 1 month prior to screening

• Currently receiving chemotherapy or radiation therapy

• Current evidence, or a history of malignancy within the past 3 years (except for nonmelanoma skin cancer or cervical cancer in situ treated with curative intent). Ifthe participant has undergone cancer treatment, this must have been completed > 3years prior to enrollment.

• Significant or chronic renal insufficiency (defined as serum creatinine > 2.5 mg/dLor an estimated glomerular filtration rate [eGFR] < 30 mL/min at screening) orrequires 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

• Body Mass Index (BMI) >35

• Known sensitivity to porcine products

• Anaphylaxis to iodine

• Pregnancy or nursing

• Substance abuse (such as alcohol or drug abuse) within 6 months prior to screening

• Any reason (in addition to those listed above) that, in the opinion of theinvestigator, precludes full participation in the study.