NCT01901094|Active Not RecruitingPhase 3DMC

Comparison of Axillary Lymph Node Dissection with Axillary Radiation for Patients with Node-Positive Breast Cancer Treated with Chemotherapy

A Randomized Phase III Trial Comparing Axillary Lymph Node Dissection to Axillary Radiation in Breast Cancer Patients (cT1-3 N1) Who Have Positive Sentinel Lymph Node Disease After Neoadjuvant Chemotherapy

Alliance for Clinical Trials in Oncology ClinicalTrials.gov

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3 other identifiers

A011202U10CA031946NCI-2013-00875

Study Type

interventional

Target

2,012

Locations

3 countries

Sites

1246

Timeline

RegisteredJul 2013

StartedFeb 2014

CompletionJan 2026

Brief Summary

This randomized phase III trial studies lymph node dissection and radiation therapy to see how well it works compared to radiation therapy alone in treating patients with breast cancer previously treated with chemotherapy and surgery. Lymph node dissection may remove cancer cells that have spread to nearby lymph nodes in patients with breast cancer. Radiation therapy uses high-energy x rays or protons to kill tumor cells. It is not yet known if radiation therapy works better alone or with lymph node dissection in treating patients with breast cancer previously treated with chemotherapy and surgery.

Trial Health

Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date

Enrollment

2,012

participants targeted

Target at P75+ for phase_3

Timeline

Completed

Started Feb 2014

Longer than P75 for phase_3

Geographic Reach

3 countries

1246 active sites

Status

active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

11.9 years study duration

First Submitted

Initial submission to the registry

July 12, 2013

Completed

5 days until next milestone

First Posted

Study publicly available on registry

July 17, 2013

Completed

7 months until next milestone

Study Start

First participant enrolled

February 24, 2014

Completed

11.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2026

Completed

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2026

Completed

Last Updated

January 13, 2025

Status Verified

January 1, 2025

Enrollment Period

11.9 years

First QC Date

July 12, 2013

Last Update Submit

January 9, 2025

Conditions

Stage II Breast Cancer Stage IIIA Breast Cancer

Outcome Measures

Primary Outcomes (1)

Invasive breast cancer recurrence-free interval (IBC-RFI)
Up to 8 years after completion of radiation therapy

Secondary Outcomes (2)

Overall survival
Up to 8 years after completion of radiation therapy
Ipsilateral/local/regional invasive breast cancer recurrence (ILR-REC)
Up to 8 years after completion of radiation therapy

Other Outcomes (4)

Development of arm lymphedema if there is a 10% increase in the volume of the ipsilateral arm from its pre-surgery volume
Up to 5 years after completion of radiation therapy
Breast lymphedema (in BCT patients)
Up to 5 years after completion of radiation therapy
Adequacy of radiation fields, dose delivered to supraclavicular and axillary nodes
Up to 8 years after completion of radiation therapy
+1 more other outcomes

Study Arms (2)

Arm 1: ALND + nodal radiation therapy

OTHER

Surgery: For patients randomized to axillary lymph node dissection (ALND), it is recommended that a complete level I and II dissection with resection of minimum of a total of 8 lymph nodes (SLN and ALND together) be done. Level III dissection is not required, but may be performed at the discretion of the surgeon. If fewer than 8 lymph nodes (SLN and ALND together) are resected, then the patient will discontinue protocol treatment. Radiation Therapy: Radiation is delivered to the breast/chest wall, undissected axilla, supraclavicular nodes and internal mammary nodes in the first 3 intercostal spaces. Treatment will be given 5 days a week over 5-6 weeks.

Procedure: Axillary Lymph Node Dissection (ALND)Radiation: Nodal Radiation Therapy

Arm 2: Axillary radiation and nodal radiation therapy

OTHER

Radiation Therapy: Radiation is delivered to the breast/chest wall, full axilla including Levels I, II, III, supraclavicular nodes and internal mammary nodes in the first 3 intercostal spaces. Treatment will be given 5 days a week over 5-6 weeks.

Radiation: Nodal Radiation TherapyRadiation: Axillary Radiation Therapy

Interventions

Axillary Lymph Node Dissection (ALND)PROCEDURE

Arm 1: ALND + nodal radiation therapy

Nodal Radiation TherapyRADIATION

Arm 1: ALND + nodal radiation therapyArm 2: Axillary radiation and nodal radiation therapy

Axillary Radiation TherapyRADIATION

Arm 2: Axillary radiation and nodal radiation therapy

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

Pre-Registration Eligibility Criteria: * Clinical stage T1-3 N1 M0 breast cancer at diagnosis (prior to the start of neoadjuvant chemotherapy) by American Joint Committee on Cancer (AJCC) staging 7th edition * No inflammatory breast cancer * No other malignancy within 5 years of registration 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 * All patients must have had an axillary ultrasound with fine needle aspiration (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 \* Note: Biopsy of intramammary nodes does not fulfill eligibility criteria * Patients must have had estrogen receptor, progesterone receptor and HER2 status (by immunohistochemistry \[IHC\] and/or in situ hybridization \[ISH\]) 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 * Patients must have completed all planned neoadjuvant chemotherapy prior to surgery; sandwich chemotherapy is not allowed (i.e. anthracycline/cytoxan or taxane chemotherapy planned to be given after surgery); patients must have completed at least 4 cycles of neoadjuvant chemotherapy consisting of an anthracycline and/or taxane-based regimen without evidence of disease progression in the breast or the lymph nodes \* Note: Delays/dose modifications due to toxicities/adverse events are allowed as long as a minimum of 4 cycles of neoadjuvant chemotherapy is administered; more than 4 cycles of neoadjuvant chemotherapy (NAC) may be administered at the discretion of the treating medical oncologist * 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 Food and Drug Administration (FDA)-approved targeted anti-HER2 therapy, but additional therapies are allowed as are non-trastuzumab regimens if administered in the context of an Institutional Review Board (IRB)-approved clinical trial * All patients must have a clinically negative axilla (no bulky adenopathy) on physical examination documented at the completion of neoadjuvant chemotherapy \* Note: an ultrasound of the axilla is not required at completion of neoadjuvant chemotherapy; if performed, its findings do NOT impact eligibility * No more than 8 weeks of neoadjuvant endocrine therapy prior to the start of neoadjuvant chemotherapy * No neoadjuvant radiation therapy * No SLN surgery/excisional biopsy for pathological confirmation of axillary status prior to or during neoadjuvant chemotherapy * No prior history of ipsilateral breast cancer (invasive disease or ductal carcinoma in situ \[DCIS\]); lobular carcinoma in situ (LCIS) and benign breast disease is allowed * No prior ipsilateral axillary surgery, such as excisional biopsy of lymph node(s) or treatment of hidradenitis * No history of prior or concurrent contralateral invasive breast cancer; benign breast disease; LCIS or DCIS of contralateral breast is allowed * Patients must not be pregnant or nursing \* Note: Peri-menopausal women must be amenorrheic for \> 12 months to be considered not of childbearing potential * Eastern Cooperative Oncology Group (ECOG) (Zubrod) performance status 0-1 Intra-Operative Registration/Randomization Criteria: * 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 * A minimum of 1 sentinel node and a maximum of 8 total nodes (sentinel + non-sentinel) are identified and excised; more than 8 nodes identified by either surgeon or pathologist is NOT allowed Note: Patients who do not have an identifiable sentinel lymph node will not proceed to registration/randomization * At least one lymph node (sentinel or non-sentinel) excised during sentinel lymph node surgery with a metastasis greater than 0.2 mm in greatest dimension identified on intra-operative pathologic assessment * Note: Isolated tumor cells (metastases less than or equal to 0.2 mm) will be treated as node negative disease (N0i+) * Note: If on final pathology, more than 8 lymph nodes are seen pathologically, then the patient should discontinue study * Axillary lymph node dissection (ALND) is not to be performed prior to registration/randomization * Note: Patients for whom no positive lymph nodes (sentinel or non-sentinel) are found during sentinel lymph node surgery will not proceed to registration/randomization and can be considered for discussion of the NRG NSABP B-51/RTOG 1304 study "A Randomized Phase III Clinical Trial Evaluating the Role of Post-mastectomy Chest Wall and Regional Nodal XRT and Post-lumpectomy Regional Nodal XRT in Patients with Documented Positive Axillary Nodes Before Neoadjuvant Chemotherapy Who Convert to Pathologically Negative Axillary Nodes After Neoadjuvant Chemotherapy" Post-Operative Registration/Randomization Criteria: * For cases where ALND has not been performed and one of the following is true: 1) intra-operative evaluation of sentinel lymph node could not be/was not performed and final pathology identified a positive lymph node (sentinel or non-sentinel) with metastasis greater than 0.2 mm OR 2) lymph node (sentinel or non-sentinel) considered negative on intra-operative evaluation was found to be positive on final pathology (with metastasis greater than 0.2 mm) * 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 * At least one lymph node (sentinel or non-sentinel) with a metastasis greater than 0.2 mm in greatest dimension identified on final pathology (for cases where intra-operative evaluation was not performed, or was negative and completion dissection was not performed) * At least one and no more than 8 lymph nodes (sentinel and non-sentinel) were found by the pathologists to have been actually excised during sentinel lymph node procedure Note: Isolated tumor cells (metastases less than or equal to 0.2 mm) will be treated as node negative disease (N0i+) * For those patients who also undergo contralateral breast surgery, if invasive disease is found in the contralateral breast, the patient is not eligible for registration /randomization

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

Alliance for Clinical Trials in Oncologylead
National Cancer Institute (NCI)collaborator
Canadian Cancer Trials Groupcollaborator

Study Sites (1246)

Southern Cancer Center PC-Daphne

Daphne, Alabama, 36526, United States

Location

Mobile Infirmary Medical Center

Mobile, Alabama, 36607, United States

Location

Southern Cancer Center PC-Mobile

Mobile, Alabama, 36607, United States

Location

Southern Cancer Center PC-Providence

Mobile, Alabama, 36608, United States

Location

Southern Cancer Center PC-Springhill

Mobile, Alabama, 36608, United States

Location

University of South Alabama Mitchell Cancer Institute

Mobile, Alabama, 36688, United States

Location

Anchorage Associates in Radiation Medicine

Anchorage, Alaska, 98508, United States

Location

Anchorage Radiation Therapy Center

Anchorage, Alaska, 99504, United States

Location

Alaska Breast Care and Surgery LLC