Axillary Node Dissection w or w/o LVB in Node Positive Breast Cancer Patients

Sponsor

Case Comprehensive Cancer Center (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05970107

Collaborator

(none)

400

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

Lymphedema is a devastating complication of breast cancer surgery that decreases the quality of life of up to 40% of breast cancer survivors. Most lymphedema in breast cancer patients is because lymphatics shared between the axilla and the arm are sacrificed during axillary lymph node dissection (ALND) surgery, which removes an average of 15 lymph nodes in node positive patients. CCF's breast cancer plastic microvascular surgeons and breast surgical oncologists have collaborated to refine a surgical technique known as LVB that may be used either as a preventive measure (prophylactic LVB) or as a therapeutic intervention (therapeutic LVB). Lymphatic reconstruction with LVB may be an improvement to the current standard of care for node positive breast cancer patients undergoing ALND.

Condition or Disease	Intervention/Treatment	Phase
Node-positive Breast Cancer	Procedure: Axillary Lymph Node Dissection Procedure: Axillary Reverse Mapping Procedure: Lymphaticovenous Bypass	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

400 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Supportive Care

Official Title:

A Prospective Randomized Trial of Axillary Node Dissection With or Without Lymphaticovenous Bypass (LVB) in Node Positive Breast Cancer Patients

Anticipated Study Start Date :

Sep 1, 2023

Anticipated Primary Completion Date :

Sep 1, 2026

Anticipated Study Completion Date :

Sep 1, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ALND + LVB The prophylactic LVB cohort will undergo ALND plus ARM and immediate lymphatic reconstruction with lymphaticovenous bypass (LVB). During the ALND, axillary reverse mapping will be used to visualize the lymphatics draining into the axilla, to aid in preserving the draining lymphatic vessels for anastomosis in LVB. Radiation therapy will be administered as determined by the treating radiation oncologist.	Procedure: Axillary Lymph Node Dissection ALND happens after cancer cells are found during a sentinel lymph node biopsy. ALND can remove lymph nodes located above, below or directly underneath a muscle that runs along the side of the upper chest. Other Names: ALND Procedure: Axillary Reverse Mapping Axillary reverse mapping (ARM) is a technique where blue dye is injected into the upper arm at surgery, allowing direct visualization of arm lymphatics and nodes during ALND Other Names: ARM Procedure: Lymphaticovenous Bypass Lymphaticovenous bypass/anastomosis (LVB/LVA) involves supramicrosurgery in which the blocked lymphatic vessel of an affected limb is connected to a nearby vein with the aid of ultra-fine instruments and a powerful operating microscope. Other Names: LVB
Active Comparator: ALND without LVB Patients in the ALND alone cohort will undergo ALND plus ARM Radiation therapy will be administered as determined by the treating radiation oncologist.	Procedure: Axillary Lymph Node Dissection ALND happens after cancer cells are found during a sentinel lymph node biopsy. ALND can remove lymph nodes located above, below or directly underneath a muscle that runs along the side of the upper chest. Other Names: ALND Procedure: Axillary Reverse Mapping Axillary reverse mapping (ARM) is a technique where blue dye is injected into the upper arm at surgery, allowing direct visualization of arm lymphatics and nodes during ALND Other Names: ARM

Arm

Intervention/Treatment

Experimental: ALND + LVB

The prophylactic LVB cohort will undergo ALND plus ARM and immediate lymphatic reconstruction with lymphaticovenous bypass (LVB). During the ALND, axillary reverse mapping will be used to visualize the lymphatics draining into the axilla, to aid in preserving the draining lymphatic vessels for anastomosis in LVB. Radiation therapy will be administered as determined by the treating radiation oncologist.

Procedure: Axillary Lymph Node Dissection

ALND happens after cancer cells are found during a sentinel lymph node biopsy. ALND can remove lymph nodes located above, below or directly underneath a muscle that runs along the side of the upper chest.

Other Names:

ALND

Procedure: Axillary Reverse Mapping

Axillary reverse mapping (ARM) is a technique where blue dye is injected into the upper arm at surgery, allowing direct visualization of arm lymphatics and nodes during ALND

Other Names:

ARM

Procedure: Lymphaticovenous Bypass

Lymphaticovenous bypass/anastomosis (LVB/LVA) involves supramicrosurgery in which the blocked lymphatic vessel of an affected limb is connected to a nearby vein with the aid of ultra-fine instruments and a powerful operating microscope.

Other Names:

LVB

Active Comparator: ALND without LVB

Patients in the ALND alone cohort will undergo ALND plus ARM Radiation therapy will be administered as determined by the treating radiation oncologist.

Procedure: Axillary Lymph Node Dissection

Other Names:

ALND

Procedure: Axillary Reverse Mapping

Axillary reverse mapping (ARM) is a technique where blue dye is injected into the upper arm at surgery, allowing direct visualization of arm lymphatics and nodes during ALND

Other Names:

ARM

Outcome Measures

Primary Outcome Measures

Rate of lymphedema onset after prophylactic LVB-Objective Criteria [At month 4 post treatment]
This is defined as a diagnosis of lymphedema by at least three of the four objective measurements performed serially every four months after baseline. The four diagnostic measurements to be performed at baseline and then every four months during the study timeframe are: a) Limb measurements; b) 3D Infrared optoelectronic volumetry (Perometer); c) Bioimpedence Spectroscopy (LDEX); d) LymphaTech handheld 3D scan.
Rate of lymphedema onset after prophylactic LVB-Objective Criteria [At month 8 post treatment]
This is defined as a diagnosis of lymphedema by at least three of the four objective measurements performed serially every four months after baseline. The four diagnostic measurements to be performed at baseline and then every four months during the study timeframe are: a) Limb measurements; b) 3D Infrared optoelectronic volumetry (Perometer); c) Bioimpedence Spectroscopy (LDEX); d) LymphaTech handheld 3D scan.
Rate of lymphedema onset after prophylactic LVB-Objective Criteria [At month 12 post treatment]
This is defined as a diagnosis of lymphedema by at least three of the four objective measurements performed serially every four months after baseline. The four diagnostic measurements to be performed at baseline and then every four months during the study timeframe are: a) Limb measurements; b) 3D Infrared optoelectronic volumetry (Perometer); c) Bioimpedence Spectroscopy (LDEX); d) LymphaTech handheld 3D scan.
Rate of lymphedema onset after prophylactic LVB-Objective Criteria [At month 16 post treatment]
This is defined as a diagnosis of lymphedema by at least three of the four objective measurements performed serially every four months after baseline. The four diagnostic measurements to be performed at baseline and then every four months during the study timeframe are: a) Limb measurements; b) 3D Infrared optoelectronic volumetry (Perometer); c) Bioimpedence Spectroscopy (LDEX); d) LymphaTech handheld 3D scan.
Rate of lymphedema onset after prophylactic LVB-Objective Criteria [At month 20 post treatment]
This is defined as a diagnosis of lymphedema by at least three of the four objective measurements performed serially every four months after baseline. The four diagnostic measurements to be performed at baseline and then every four months during the study timeframe are: a) Limb measurements; b) 3D Infrared optoelectronic volumetry (Perometer); c) Bioimpedence Spectroscopy (LDEX); d) LymphaTech handheld 3D scan.
Rate of lymphedema onset after prophylactic LVB-Objective Criteria [At month 24 post treatment]
This is defined as a diagnosis of lymphedema by at least three of the four objective measurements performed serially every four months after baseline. The four diagnostic measurements to be performed at baseline and then every four months during the study timeframe are: a) Limb measurements; b) 3D Infrared optoelectronic volumetry (Perometer); c) Bioimpedence Spectroscopy (LDEX); d) LymphaTech handheld 3D scan.
Rate of lymphedema onset after prophylactic LVB-Objective Criteria [At month 27 post treatment]
This is defined as a diagnosis of lymphedema by at least three of the four objective measurements performed serially every four months after baseline. The four diagnostic measurements to be performed at baseline and then every four months during the study timeframe are: a) Limb measurements; b) 3D Infrared optoelectronic volumetry (Perometer); c) Bioimpedence Spectroscopy (LDEX); d) LymphaTech handheld 3D scan.
Rate of lymphedema onset after prophylactic LVB-Subjective Criteria [At month 4 post treatment]
The patient-reported outcomes survey Lymph-ICF-UL will be used to compare subjective symptoms of lymphedema to the four diagnostic measurements to determine which is the most sensitive and evaluate the concordance of these tests.
Rate of lymphedema onset after prophylactic LVB-Subjective Criteria [At month 8 post treatment]
The patient-reported outcomes survey Lymph-ICF-UL will be used to compare subjective symptoms of lymphedema to the four diagnostic measurements to determine which is the most sensitive and evaluate the concordance of these tests.
Rate of lymphedema onset after prophylactic LVB-Subjective Criteria [At month 12 post treatment]
The patient-reported outcomes survey Lymph-ICF-UL will be used to compare subjective symptoms of lymphedema to the four diagnostic measurements to determine which is the most sensitive and evaluate the concordance of these tests.
Rate of lymphedema onset after prophylactic LVB-Subjective Criteria [At month 16 post treatment]
The patient-reported outcomes survey Lymph-ICF-UL will be used to compare subjective symptoms of lymphedema to the four diagnostic measurements to determine which is the most sensitive and evaluate the concordance of these tests.
Rate of lymphedema onset after prophylactic LVB-Subjective Criteria [At month 20 post treatment]
The patient-reported outcomes survey Lymph-ICF-UL will be used to compare subjective symptoms of lymphedema to the four diagnostic measurements to determine which is the most sensitive and evaluate the concordance of these tests.
Rate of lymphedema onset after prophylactic LVB-Subjective Criteria [At month 24 post treatment]
The patient-reported outcomes survey Lymph-ICF-UL will be used to compare subjective symptoms of lymphedema to the four diagnostic measurements to determine which is the most sensitive and evaluate the concordance of these tests.
Rate of lymphedema onset after prophylactic LVB-Subjective Criteria [At month 27 post treatment]
The patient-reported outcomes survey Lymph-ICF-UL will be used to compare subjective symptoms of lymphedema to the four diagnostic measurements to determine which is the most sensitive and evaluate the concordance of these tests.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Subjects must have histologically or cytologically confirmed axillary node positive unilateral breast cancer and may be female or male.
Subjects must have received no prior surgical interventions to the axilla except for core needle biopsy or sentinel node biopsy within 30 days of the planned axillary node dissection.
Age >18 years. Children are excluded from this study since breast cancer is quite rare in children.
ECOG Performance status 0 or 1
Subjects must have normal organ and marrow function as defined below:
Leukocytes ≥ 3,000/mcL
Absolute neutrophil count ≥ 1,500/mcL
Platelet count ≥ 100,000/mcL
Total bilirubin within normal institutional limits
AST (SGOT) ≤ 2.5 X institutional upper limit of normal
ALT (SGPT) ≤ 2.5 X institutional upper limit of normal
Serum Creatinine within normal institutional limits
Subjects must have at least one suitable lymphatic and one suitable vein amenable to lymphovenous bypass anastomosis.
Subjects must have the ability to understand and the willingness to sign a written informed consent document.
Patients may be treated with adjuvant or neoadjuvant therapies at the discretion of the treating medical oncologist
Patients may be treated with adjuvant radiation therapy at the discretion of the treating radiation oncologist.
Patients may be treated with either mastectomy or breast conserving surgery at the discretion of the treating surgical oncologist.
In order to complete the Lymph-ICF-UL questionnaire, participants must be able to speak and/or read English.
Healthy controls include women aged 18-75 without a current or past history of breast cancer or lymphedema who are willing to undergo blood draw.

Exclusion Criteria:

Contraindication to ICG as a) iodine hypersensitivity, b) renal failure, c) uremia and

on dialysis.

Subjects receiving any prior surgical treatment or radiation to the axilla prior to protocol enrollment (except sentinel node biopsy within the past 30 days).
Subjects with known regional cervical or supraclavicular nodal disease or distant metastatic disease.
History of allergic reactions attributed to compounds of similar chemical or biologic composition to isosulfan blue dye or other agents used in this study.
History of pre-existing lymphedema or measured lymphedema at baseline upon study enrollment
BMI greater than or equal to 40.
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
History of pulmonary embolism or deep venous thrombosis
Patients must not be on anticoagulant therapy with warfarin, clopidogrel (Plavix), apixavan (Eliquis), heparin, low molecular weight heparin, rivaroxaban (Xarelto), ticlodipine (Ticlid), fonduparinux (Arixtra) with the exception of routine heparin flushes to a portacath.
Patients treated with sentinel lymph node biopsy only without ALND
Arteriovenous fistula or the presence of an indwelling peripherally inserted central catheter (PICC line), or the presence of a central venous line or portacath in the ipsilateral arm.
ECOG performance status of 2 or higher.
Pregnant or breast-feeding women are excluded from the study given that it is unknown whether isosulfan blue can cause fetal harm and it is desirable to limit anesthesia time in this population
Less than 18 years of age or greater than 75 years of age.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Case Comprehensive Cancer Center

Investigators

Principal Investigator: Julie E Lang, MD, FACS, Cleveland Clinic Foundation: Digestive Disease & Surgery Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Case Comprehensive Cancer Center

ClinicalTrials.gov Identifier:

NCT05970107

Other Study ID Numbers:

CASE2123

First Posted:

Aug 1, 2023

Last Update Posted:

Aug 1, 2023

Last Verified:

Jul 1, 2023

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Case Comprehensive Cancer Center

Prophylactic Lymphaticovenous Bypass

Additional relevant MeSH terms:

Breast Neoplasms

Study Results

No Results Posted as of Aug 1, 2023