Axillary Reverse Mapping in Preventing Lymphedema in Patients With Breast Cancer Undergoing Axillary Lymph Node Dissection

Breast Cancer Stage II Clinical Trial

Official title:

ARM: Axillary Reverse Mapping - A Prospective Trial to Study Rates of Lymphedema and Regional Recurrence After Sentinel Lymph Node Biopsy and Sentinel Lymph Node Biopsy Followed by Axillary Lymph Node Dissection With and Without Axillary Reverse Mapping

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03927027
• Other study ID #: A221702
• Secondary ID: NCI-2018-02445UG
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: July 29, 2019
• Est. completion date: January 2026

Study information

• Verified date: April 2024
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase III trial studies how well axillary reverse mapping works in preventing lymphedema in patients with breast cancer undergoing axillary lymph node dissection. Axillary reverse mapping may help to preserve the lymph node drainage system around the breast so as to prevent lymphedema after surgery.

Description:

PRIMARY OBJECTIVES:

I. To determine the occurrence of post-surgery lymphedema by conical geometric measures in clinical T1-3, N0-3, M0 breast cancer patients undergoing axillary surgery and randomized to Group 1 (no axillary reverse mapping [ARM]) versus Group II (ARM).

SECONDARY OBJECTIVES:

I. To compare between the study groups the lymphedema symptom intensity and distress as measured by the Lymphedema Symptom Intensity and Distress Survey-Arm (LSIDS-A).

II. To evaluate the technical success of performance of ARM procedure: Identification of ARM lymphatics, and the ability to spare or reapproximate ARM lymphatics.

III. To compare the rate of regional recurrence between patients randomized to receive ARM versus no ARM.

EXPLORATORY OBJECTIVES:

I. To assess the occurrence of lymphedema as a function of radiotherapy use and targets.

OUTLINE: Patients are randomized to 1 of 2 groups.

GROUP I: Patients receive isosulfan blue subcutaneously (SC) and undergo axillary lymph node dissection (ALND).

GROUP II: Patients undergo ARM. Patients then receive isosulfan blue and undergo ALND as in Group I.

After completion of study, patients are followed up for 3 years.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 534
• Est. completion date: January 2026
• Est. primary completion date: November 26, 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Documentation of Disease: cT1-3 patients undergoing axillary surgery who additionally meet one of the following conditions:

• Clinically node negative patients undergoing mastectomy and sentinel lymph node biopsy (SLNB) with possible axillary lymph node dissection (ALND) if SLNB is positive. If ALND is performed during a separate operation, ARM procedure must be repeated. Clinically node negative is defined by i) negative clinical exam and/or ii) negative axillary US and/or iii) negative needle biopsy of sonographically suspicious axillary nodes as applicable to each case.

• Clinically node positive patients as determined by needle biopsy and planned for ALND regardless of type of breast surgery.

• Patients will be staged according to the TNM staging system.

• Prior Treatment: No prior axillary surgery except needle biopsy or concurrent SLNB.

o Prior neoadjuvant chemotherapy is allowed but must be completed at least 2 weeks before registration.

• No prior history of ipsilateral breast cancer (invasive or ductal breast carcinoma in situ [DCIS]). Lobular breast carcinoma in situ (LCIS) and benign disease are allowed. (May have neoadjuvant chemotherapy which must be completed 2 weeks before registration).

• No bilateral invasive breast cancer.

• No matted nodes.

• No history of lymphedema of either arm.

• No known allergies blue dyes, including make-up containing blue dye.

• In order to complete the mandatory patient-completed measures, participants must be able to speak and/or read English.

• Female :

Men are excluded from this study because the number of men with breast cancer is insufficient to provide a statistical basis for assessment of effects in this subpopulation of people with breast cancer.

• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2.

• Creatinine: =< 1.5 x upper limit of normal (ULN).

Related Conditions & MeSH terms

• Breast Cancer Stage I
• Breast Cancer Stage II
• Breast Cancer Stage III
• Breast Neoplasms
• Lymphedema

Intervention

Drug:
• Isosulfan Blue
Given SC

Procedure:
• Axillary Lymph Node Dissection
Undergo ALND
• Mapping
Undergo ARM

Other:
• Quality-of-Life Assessment
Ancillary studies
• Questionnaire Administration
Ancillary studies

Locations

Country	Name	City	State
United States	Cleveland Clinic Akron General	Akron	Ohio
United States	UTMB Health Angleton Danbury Campus	Angleton	Texas
United States	Anne Arundel Medical Center	Annapolis	Maryland
United States	McLaren Cancer Institute-Bay City	Bay City	Michigan
United States	UHHS-Chagrin Highlands Medical Center	Beachwood	Ohio
United States	Ascension Southeast Wisconsin Hospital - Elmbrook Campus	Brookfield	Wisconsin
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Geauga Hospital	Chardon	Ohio
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Cincinnati Cancer Center-UC Medical Center	Cincinnati	Ohio
United States	Case Western Reserve University	Cleveland	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Henry Ford Macomb Hospital-Clinton Township	Clinton Township	Michigan
United States	Mount Carmel East Hospital	Columbus	Ohio
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	MD Anderson in The Woodlands	Conroe	Texas
United States	UM Sylvester Comprehensive Cancer Center at Coral Gables	Coral Gables	Florida
United States	Parkland Memorial Hospital	Dallas	Texas
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	UM Sylvester Comprehensive Cancer Center at Deerfield Beach	Deerfield Beach	Florida
United States	Henry Ford Hospital	Detroit	Michigan
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	Cancer Institute at Saint Francis Hospital	East Hills	New York
United States	Shaw Cancer Center	Edwards	Colorado
United States	Weisberg Cancer Treatment Center	Farmington Hills	Michigan
United States	Piedmont Fayette Hospital	Fayetteville	Georgia
United States	Holy Cross Hospital	Fort Lauderdale	Florida
United States	Beebe South Coastal Health Campus	Frankford	Delaware
United States	University of Florida Health Science Center - Gainesville	Gainesville	Florida
United States	University of Texas Medical Branch	Galveston	Texas
United States	Goshen Center for Cancer Care	Goshen	Indiana
United States	Aurora Cancer Care-Grafton	Grafton	Wisconsin
United States	Aurora BayCare Medical Center	Green Bay	Wisconsin
United States	Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center	Houston	Texas
United States	M D Anderson Cancer Center	Houston	Texas
United States	MD Anderson West Houston	Houston	Texas
United States	Swedish Cancer Institute-Issaquah	Issaquah	Washington
United States	Baptist MD Anderson Cancer Center	Jacksonville	Florida
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	MD Anderson League City	League City	Texas
United States	UTMB Cancer Center at Victory Lakes	League City	Texas
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	The James Graham Brown Cancer Center at University of Louisville	Louisville	Kentucky
United States	Contra Costa Regional Medical Center	Martinez	California
United States	UH Seidman Cancer Center at Lake Health Mentor Campus	Mentor	Ohio
United States	UM Sylvester Comprehensive Cancer Center at Kendall	Miami	Florida
United States	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida
United States	UH Seidman Cancer Center at Southwest General Hospital	Middleburg Heights	Ohio
United States	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin
United States	Aurora Sinai Medical Center	Milwaukee	Wisconsin
United States	Mount Carmel New Albany Surgical Hospital	New Albany	Ohio
United States	NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center	New York	New York
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Helen F Graham Cancer Center	Newark	Delaware
United States	Advocate Christ Medical Center	Oak Lawn	Illinois
United States	Alta Bates Summit Medical Center - Summit Campus	Oakland	California
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Orlando Health Cancer Institute	Orlando	Florida
United States	University of Kansas Hospital-Indian Creek Campus	Overland Park	Kansas
United States	University Hospitals Parma Medical Center	Parma	Ohio
United States	Penn Presbyterian Medical Center	Philadelphia	Pennsylvania
United States	Pennsylvania Hospital	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania
United States	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania
United States	UM Sylvester Comprehensive Cancer Center at Plantation	Plantation	Florida
United States	Women and Infants Hospital	Providence	Rhode Island
United States	University Hospitals Portage Medical Center	Ravenna	Ohio
United States	Beebe Health Campus	Rehoboth Beach	Delaware
United States	VCU Massey Cancer Center at Stony Point	Richmond	Virginia
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	Pluta Cancer Center	Rochester	New York
United States	University of Rochester	Rochester	New York
United States	UH Seidman Cancer Center at Firelands Regional Medical Center	Sandusky	Ohio
United States	Saint John's Cancer Institute	Santa Monica	California
United States	Swedish Medical Center-First Hill	Seattle	Washington
United States	Sidney Kimmel Cancer Center Washington Township	Sewell	New Jersey
United States	Robert Wood Johnson University Hospital Somerset	Somerville	New Jersey
United States	MD Anderson in Sugar Land	Sugar Land	Texas
United States	University Hospitals Sharon Health Center	Wadsworth	Ohio
United States	Ascension Medical Group Southeast Wisconsin - Mayfair Road	Wauwatosa	Wisconsin
United States	Aurora West Allis Medical Center	West Allis	Wisconsin
United States	Henry Ford West Bloomfield Hospital	West Bloomfield	Michigan
United States	University of Cincinnati Cancer Center-West Chester	West Chester	Ohio
United States	Good Samaritan Hospital Medical Center	West Islip	New York
United States	UH Seidman Cancer Center at Saint John Medical Center	Westlake	Ohio
United States	UHHS-Westlake Medical Center	Westlake	Ohio
United States	University of Kansas Hospital-Westwood Cancer Center	Westwood	Kansas
United States	Geisinger South Wilkes-Barre	Wilkes-Barre	Pennsylvania
United States	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania
United States	Asplundh Cancer Pavilion	Willow Grove	Pennsylvania
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Henry Ford Wyandotte Hospital	Wyandotte	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of upper extremity (UE) lymphedema	Will be assessed by the Lymphedema Symptom Intensity and Distress Survey-Arm (LSIDS-A). The LSIDS-A questionnaire contains two different scales for intensity and distress measured from 1 (slight) to 5 (severe). The LSIDS-A questionnaire scores for swelling in the arm, decreased physical activity, pain in the arm, and loss of confidence in one's body will be evaluated for the change of baseline to 36 months using a two-sample, two-sided t-test.	Up to 36 months post surgery
Secondary	Change in health-related quality of life: LSIDS-A questionnaire scores	Will be assessed by the Lymphedema Symptom Intensity and Distress Survey-Arm (LSIDS-A). The LSIDS-A questionnaire scores at each time point, as well as the change from baseline will be compared between groups by a two-sample, two-sided t-test. If there is evidence of non-normality (via Shapiro-Wilk testing), will use a non-parametric procedure such as Wilcoxon rank sum test. Further analysis will include linear mixed model using data from all time points to compare the LSIDS-A questionnaire scores between the two treatment groups over time adjusting for other baseline characteristics. Will evaluate the pattern of missing data. If the drop-out rate is higher than expected, methods proposed by Hogan and Laird will be used to assess whether the presence of drop-outs affects inferences obtained from the repeated measures analyses. Appropriate methods will be used to address missingness.	Baseline to 36 months
Secondary	Incidence of regional recurrence	The technical success will be summarized using a binomial point estimate and 95% confidence interval (CI) and will be compared using a two-sample test of proportions.	Up to 3 years
Secondary	Technical success of performance of axillary reverse mapping (ARM) procedure (defined as identification of ARM lymphatics, and the ability to spare or reapproximate ARM lymphatics)	The cumulative incidence of regional recurrence will be summarized using the cumulative incidence function treating death without regional recurrence as the competing risk. Similar analysis methods described for the primary endpoint will be used to compare the cumulative incidence of regional recurrence between group I and II.	Up to 3 years