De-Escalation of Axillary Management in Advanced Nodal Disease (DEMAND)

June 8, 2026 updated by: Jamie Wagner, D.O., University of Kansas Medical Center

DEMAND - A Phase II Trial of De-Escalation of Axillary Management in Advanced Nodal Disease

This is a prospective, phase 2, single arm trial to evaluate whether Axillary Lymph Node Dissection (ALND) can be safely omitted for patients with cN2 and cN3 breast cancer who achieve a complete clinical response on exam with a complete or partial response by end-of-treatment (EOT) imaging and have either a partial or complete pathologic nodal response after neoadjuvant chemotherapy (NAC) by performing nodal assessment of sentinel lymph node surgery (with or without targeted axillary dissection (TAD) followed by Regional Nodal Irradiation (RNI).

This study aims to demonstrate that performing only a sentinel node dissection, which includes the removal of palpably gross disease followed by radiation, will not impact distant disease and thus survival.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

120

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Ability of participant to understand this study, and participant willingness to sign a written informed consent. NOTE Remote consenting allowed per IRB policy and approval.
  2. Stated willingness to comply with all study procedures and lifestyle considerations and availability for the duration of the study
  3. Males and/or females age ≥ 18 to 80 years
  4. Clinical stage T1-3 N2-3 M0 breast cancer at diagnosis (prior to the start of neoadjuvant chemotherapy).
  5. Patients stage T1-3 cN1 (prior to start of neoadjuvant chemotherapy) and pN2-3 breast cancer based on number of positive nodes on final surgical pathology.
  6. All patients must have had an axillary ultrasound with FNA or core needle biopsy of axillary lymph nodes documenting axillary metastasis at the time of diagnosis, prior to or at most 14 days after starting neoadjuvant chemotherapy.
  7. Patients must have had estrogen receptor, progesterone receptor and HER2 status (by IHC and/or ISH) evaluated on diagnostic core biopsy prior to start of neoadjuvant chemotherapy. Note: If HER2 status has not been clearly determined (i.e. equivocal/indeterminate), then patients should not be enrolled (see exclusion criteria).
  8. Patients must have completed planned chemotherapy (neoadjuvant chemotherapy [NAC]) prior to surgery. Sandwich chemotherapy is not allowed (i.e. chemotherapy planned to be given after surgery). Adjuvant systemic therapy based on final surgical pathology is allowed and at the discretion of the treating medical oncologist. Note: Delays/dose modifications due to toxicities/adverse events are allowed per the treating medical oncologist.
  9. Patients with HER-2 positive tumors must have received neoadjuvant trastuzumab, or trastuzumab + pertuzumab, or other approved anti-HER-2 therapy (either with all or with a portion of the neoadjuvant chemotherapy regimen). Therapy must be FDA-approved targeted anti-HER2 therapy, but additional therapies are allowed as are non-trastuzumab regimens if administered in the context of an IRB-approved clinical trial.
  10. Benign breast disease, LCIS or DCIS of contralateral breast is allowed
  11. All patients must have a clinically negative axilla (no bulky adenopathy) on physical examination documented at the completion of neoadjuvant chemotherapy. Note: A partial or complete imaging response that includes all lymph nodes measuring ≤ 1cm clinically is required for eligibility.
  12. ECOG (Zubrod) Performance Status 0-1 (Appendix A)
  13. A minimum of 1 sentinel node must be identified and excised by the surgeon. Patients who do not have an identifiable sentinel lymph node will not proceed to omission of ALND.
  14. Patients that have a pathologic complete response (pCR) in the breast and axilla can be considered for discussion at the Breast Multidisciplinary Tumor Conference for omission of radiation. Note: Isolated tumor cells (metastases less than or equal to 0.2 mm) will be treated as node negative disease (N0i+).
  15. Breast surgery (lumpectomy or mastectomy) and sentinel lymph node surgery must be completed within 56 days of the completion of the last dose of neoadjuvant chemotherapy. Negative margin (by either breast conservation or mastectomy) on final pathology where negative margin is defined as no tumor on ink.
  16. Females of childbearing potential must have a negative serum pregnancy at day of surgery in pre-operative holding prior to initiating treatment.
  17. Females of child-bearing potential and males with partners of child-bearing potential must agree not to donate sperm, to practice sexual abstinence or to use the forms of contraception listed in Child-Bearing Potential/Pregnancy section for the duration of study participation and, following the last administration of therapy , for as long as directed per standard or care chemotherapy (investigational regimen allowed) and radiation therapy, whichever is longer. Note: Peri-menopausal women must be amenorrheic for ≥ 12 months to be considered not of childbearing potential.

Definition of medically fit for surgery:

  • ECOG status of 0-1
  • NOTE - participants are eligible for surgery if they have nicotine in the blood or high A1c. These values will be monitored per SOC.

Exclusion Criteria:

  1. Diagnosed with a psychiatric illness or is in a social situation that would limit compliance with study requirements and / or giving informed consent.
  2. Medical condition such as uncontrolled infection (including HIV), uncontrolled diabetes mellitus or cardiac disease which, in the opinion of the treating physician, would make this study unreasonably hazardous for the patient.
  3. Inflammatory breast cancer.
  4. Any other malignancy within 5 years of enrollment with the exception of basal cell or squamous cell carcinoma of the skin treated with local resection only or carcinoma in situ of the cervix.
  5. HER2 status has not been clearly determined (i.e. equivocal/indeterminate)
  6. Patient has had neoadjuvant endocrine therapy > than 8 weeks prior to the start of neoadjuvant chemotherapy.
  7. Neoadjuvant radiation therapy.
  8. SLN surgery/excisional biopsy for pathological confirmation of axillary status prior to or during neoadjuvant chemotherapy.
  9. Prior history of ipsilateral breast cancer (invasive disease or DCIS). NOTE LCIS and benign breast disease is allowed.
  10. Prior ipsilateral axillary surgery, such as excisional biopsy of lymph node(s) or treatment of hidradenitis.
  11. History of prior or concurrent contralateral invasive breast cancer. .
  12. Patient pregnant or nursing.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Axillary Surgery
Procedure: Axillary Surgery
Patients who are clinically node negative after neoadjuvant chemotherapy by physical examination will undergo clinically indicated breast surgery (mastectomy or lumpectomy) with sentinel lymph node (SLN) surgery. Sentinel lymph node surgery must be performed within 8 weeks (56 days) after completion of the last dose of neoadjuvant chemotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease Free Survival (DFS)
Time Frame: 5 years
To determine if radiation to the undissected axilla and regional lymph nodes is not inferior to axillary lymph node dissection with regional nodal irradiation (excluding dissected axilla) for DFS after neoadjuvant chemotherapy response. DFS assessed according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v6.0.
5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Invasive Breast Cancer Recurrence Free Interval (IBC - RFI)
Time Frame: 5 years
To assess if radiation to the undissected axilla and regional nodes is not inferior to axillary dissection plus regional nodal radiation for IBC-RFI, DSS, and LRR in patients with complete or partial response to neoadjuvant chemotherapy. Determined by medical record.
5 years
Disease Specific Survival (DSS)
Time Frame: 5 years
To assess if radiation to the undissected axilla and regional nodes is not inferior to axillary dissection plus regional nodal radiation for IBC-RFI, DSS, and LRR in patients with complete or partial response to neoadjuvant chemotherapy. Determined by medical record.
5 years
Locoregional Recurrence (LRR)
Time Frame: 5 years
To assess if radiation to the undissected axilla and regional nodes is not inferior to axillary dissection plus regional nodal radiation for IBC-RFI, DSS, and LRR in patients with complete or partial response to neoadjuvant chemotherapy. Determined by medical record.
5 years
Lymphedema Incidence
Time Frame: Measured at 9 months, annually, and PRN (as needed) per patient reported symptoms, over a duration of approximately 5 years.
To estimate the incidence of arm lymphedema in participants that undergo SLN with comprehensive RNI. Determined by Bioimpedance Spectroscopy
Measured at 9 months, annually, and PRN (as needed) per patient reported symptoms, over a duration of approximately 5 years.
Recurrence Cancer Burden (RCB) Score
Time Frame: Measured at final surgical pathology (up to 21 days after surgery)
To estimate the distribution or Recurrence Cancer Burden (RCB) Score
Measured at final surgical pathology (up to 21 days after surgery)
Imaging positive predictive value for extent of nodal disease burden compared to final surgical pathology and lab draws
Time Frame: Measured at final surgical pathology (up to 21 days after surgery)
Assessed by MRI, US, and final surgical pathology. The same imaging modality used to assess nodal adenopathy at baseline must be used throughout. RECIST v 1.1 criteria will be used for assessments.
Measured at final surgical pathology (up to 21 days after surgery)

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
ctDNA Analysis
Time Frame: ctDNA will be collected prior to start of neoadjuvant chemotherapy, day of surgery, and within 30 days of completing radiation therapy
To evaluate ctDNA following neoadjuvant chemotherapy in participants with locally advanced breast cancer
ctDNA will be collected prior to start of neoadjuvant chemotherapy, day of surgery, and within 30 days of completing radiation therapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Kansas Medical Center

Investigators

  • Principal Investigator: Jamie Wagner, D.O., The University of Kansas Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

July 1, 2026

Primary Completion (Estimated)

July 1, 2031

Study Completion (Estimated)

July 1, 2031

Study Registration Dates

First Submitted

May 29, 2026

First Submitted That Met QC Criteria

June 8, 2026

First Posted (Actual)

June 11, 2026

Study Record Updates

Last Update Posted (Actual)

June 11, 2026

Last Update Submitted That Met QC Criteria

June 8, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IIT-2025-DEMAND

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

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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