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

Phase 3

Active, not recruiting

• Conditions: Breast Cancer Stage II; Breast Cancer Stage I; Breast Cancer Stage III
• Interventions: Drug: Isosulfan Blue; Procedure: Axillary Lymph Node Dissection; Other: Quality-of-Life Assessment; Procedure: Mapping; Other: Questionnaire Administration

• Registration Number: NCT03927027
• Lead Sponsor: Alliance for Clinical Trials in Oncology

Brief 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.

Detailed 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.

Study Timeline

• Study First Submitted: 2019-04-23
• Study First Submitted QC: 2019-04-24
• Study First Posted: 2019-04-25
• Study Start: 2019-07-29
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-15
• Last Update Posted: 2025-01-17
• Primary Completion: 2026-11-26
• Study Completion: 2027-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Female
• Target Recruitment: 534

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).

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group I (ALND)	Axillary Lymph Node Dissection	Patients receive isosulfan blue SC and undergo ALND.
Group II (ARM, ALND)	Axillary Lymph Node Dissection	Patients undergo ARM. Patients then receive isosulfan blue and undergo ALND as in Group I.
Group II (ARM, ALND)	Questionnaire Administration	Patients undergo ARM. Patients then receive isosulfan blue and undergo ALND as in Group I.
Group I (ALND)	Quality-of-Life Assessment	Patients receive isosulfan blue SC and undergo ALND.
Group I (ALND)	Questionnaire Administration	Patients receive isosulfan blue SC and undergo ALND.
Group II (ARM, ALND)	Mapping	Patients undergo ARM. Patients then receive isosulfan blue and undergo ALND as in Group I.
Group II (ARM, ALND)	Quality-of-Life Assessment	Patients undergo ARM. Patients then receive isosulfan blue and undergo ALND as in Group I.
Group II (ARM, ALND)	Isosulfan Blue	Patients undergo ARM. Patients then receive isosulfan blue and undergo ALND as in Group I.
Group I (ALND)	Isosulfan Blue	Patients receive isosulfan blue SC and undergo ALND.

Primary Outcome Measures

Name	Time	Method
Incidence of upper extremity (UE) lymphedema	Up to 36 months post surgery	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.

Secondary Outcome Measures

Name	Time	Method
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)	Up to 3 years	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.
Change in health-related quality of life: LSIDS-A questionnaire scores	Baseline to 36 months	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.
Incidence of regional recurrence	Up to 3 years	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.

Trial Locations

Locations (96)

University of Arkansas for Medical Sciences; 🇺🇸 Little Rock, Arkansas, United States

UC San Diego Moores Cancer Center; 🇺🇸 La Jolla, California, United States

Contra Costa Regional Medical Center; 🇺🇸 Martinez, California, United States

Alta Bates Summit Medical Center - Summit Campus; 🇺🇸 Oakland, California, United States

Saint John's Cancer Institute; 🇺🇸 Santa Monica, California, United States

Shaw Cancer Center; 🇺🇸 Edwards, Colorado, United States

Beebe South Coastal Health Campus; 🇺🇸 Frankford, Delaware, United States

Helen F Graham Cancer Center; 🇺🇸 Newark, Delaware, United States

Christiana Care Health System-Christiana Hospital; 🇺🇸 Newark, Delaware, United States

Beebe Health Campus; 🇺🇸 Rehoboth Beach, Delaware, United States

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