Trial record 1 of 1 for:    NCT 01901094
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Comparison of Axillary Lymph Node Dissection With Axillary Radiation for Patients With Node-Positive Breast Cancer Treated With Chemotherapy

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Alliance for Clinical Trials in Oncology
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT01901094
First received: July 12, 2013
Last updated: June 25, 2014
Last verified: June 2014
  Purpose

This randomized phase III trial studies axillary lymph node dissection to see how well it works compared to axillary radiation therapy alone in treating patients with node-positive breast cancer previously treated with neoadjuvant chemotherapy followed by 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 to kill tumor cells. This study will evaluate whether radiation therapy is as effective as lymph node dissection.


Condition Intervention Phase
Lymphedema
Stage IA Breast Cancer
Stage IB Breast Cancer
Stage II Breast Cancer
Stage IIIA Breast Cancer
Procedure: Axillary Lymph Node Dissection
Radiation: Nodal Radiation Therapy
Radiation: Axillary Radiation Therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase III Trial Evaluating the Role of Axillary Lymph Node Dissection in Breast Cancer Patients (cT1-3 N1) Who Have Positive Sentinel Lymph Node Disease After Neoadjuvant Chemotherapy

Resource links provided by NLM:


Further study details as provided by Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • Invasive breast cancer recurrence-free interval (IBC-RFI) [ Time Frame: Time from randomization to the first of the following events: invasive ipsilateral, local, regional, or distant recurrence and death due to breast cancer or treatment, assessed up to 5 years after completion of radiation therapy ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: Up to 5 years after completion of radiation therapy ] [ Designated as safety issue: No ]
  • Ipsilateral/local/regional invasive breast cancer recurrence (ILR-REC) [ Time Frame: Up to 5 years after completion of radiation therapy ] [ Designated as safety issue: No ]
  • Development of arm lymphedema, defined as a 10 % increase in the volume of the ipsilateral arm from its pre-surgery volume using the Breast Lymphedema Symptom Survey [ Time Frame: Up to 2 years post surgery ] [ Designated as safety issue: No ]
  • Development of breast lymphedema (in BCT patients) using the Breast Lymphedema Symptom Survey [ Time Frame: Up to 2 years post surgery ] [ Designated as safety issue: No ]
  • Radiation dose delivered to supraclavicular and axillary nodes [ Time Frame: Up to 6 weeks post surgery ] [ Designated as safety issue: No ]
  • Residual cancer burden (RCB) [ Time Frame: Up to 6 weeks prior to radiation therapy ] [ Designated as safety issue: No ]

Estimated Enrollment: 2918
Study Start Date: February 2014
Estimated Primary Completion Date: January 2024 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Axillary lymph node dissection + nodal radiation therapy

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. 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 Radiation: Nodal Radiation Therapy
Experimental: Axillary radiation and nodal radiation therapy only
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 Therapy Radiation: Axillary Radiation Therapy

Detailed Description:

All patients will undergo surgery to identify sentinel lymph node(s). If a sentinel lymph node is determined to be positive on intra-operative pathology the patient will be registered/randomized intra-operatively. Patients who do not have a sentinel lymph node identified will not be registered/randomized to the study. Patients whose sentinel lymph is found to be negative intra-operatively and have not undergone ALND, but had at least one sentinel lymph node found to be positive on final pathology review will be registered/randomized post-operatively. After patient registration/randomization, if negative surgical margins are not achieved at the completion of all breast surgeries then the patient will discontinue protocol treatment.

Patients with hormone receptor (ER and/or PR) positive disease should receive a minimum of 5 years of standard endocrine therapy (experimental agents/regimens are not permitted). Endocrine therapy should begin following completion of neoadjuvant chemotherapy and surgery, either before, during or after radiation therapy at the discretion of the oncologist. Selection of the agents is at the treating physician's discretion.

Patients with HER 2 positive disease (on tumor markers obtained either prior to NAC or on surgical pathology) should complete a total of one year of trastuzumab therapy (over the neoadjuvant and adjuvant period). Chemotherapy, biologic therapy or vaccine therapy in the adjuvant setting is not allowed. Patients who wish to receive any of these therapies after surgery must go off study at the time of their initiation.

Primary Objective:

  • To evaluate whether radiation to the undissected axilla and regional lymph nodes is not inferior to axillary lymph node dissection with radiation to the regional lymph nodes but not to the dissected axilla in terms of invasive breast cancer recurrence-free interval in patients with positive SLN(s) after completion of neoadjuvant chemotherapy

Secondary Objectives:

  • To evaluate whether radiation to the undissected axilla and regional lymph nodes is not inferior to axillary lymph node dissection with radiation to the regional lymph nodes but not to the dissected axilla in terms of the incidence of invasive loco-regional recurrences in patients with a positive SLN(s) after completion of neoadjuvant chemotherapy
  • To obtain an estimate of the distribution of residual disease burden scores.
  • To estimate the distribution of overall survival.

Patients are followed up for 5 years after completion of radiation therapy.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Pre-Registration Eligibility Criteria:

  • Patients ≥ 18 years of age
  • 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 neoadjuvant chemotherapy.
  • Patients must have had estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 (HER2) status by immunohistochemistry [IHC] or fluorescence in situ hybridization [FISH] evaluated on diagnostic core biopsy prior to start of neoadjuvant chemotherapy.
  • Patients must have completed all planned chemotherapy prior to surgery. Sandwich chemotherapy is not allowed (i.e. chemotherapy planned to be given after surgery). Patients must have completed at least 6 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.
  • Patients with HER-2 positive tumors must have received neoadjuvant trastuzumab, 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 palpable lymph nodes or bulky adenopathy) on physical examination documented at the completion of neoadjuvant chemotherapy.
  • No neoadjuvant endocrine therapy.
  • No neoadjuvant radiation therapy.
  • No sentinel lymph node (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. A negative pregnancy test is required prior to registration for women of childbearing potential. 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.
  • Required Pre-Registration Laboratory Values:

    1. Serum or urine beta-human chorionic gonadotropin (ß-HCG)
    2. Negative in women of child-bearing potential

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 neoadjuvant chemotherapy.
  • A minimum of 2 or a maximum of 6 sentinel nodes are identified and excised by the surgeon. Patients who do not have an identifiable sentinel lymph node will not proceed to Registration/Randomization.
  • At least one sentinel lymph node 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+). Axillary lymph node dissection [ALND] is not to be performed prior to Registration/Randomization.

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 SLN with metastasis greater than 0.2 mm on hematoxylin and eosin stain (H & E) OR
    2. sentinel lymph node on intra-operative evaluation considered negative was found to be positive on final pathology (with metastasis greater than 0.2 mm on H & E).
  • Breast surgery (lumpectomy or mastectomy) and sentinel lymph node surgery must be completed within 56 days of the completion of neoadjuvant chemotherapy.
  • At least one lymph node with a metastasis greater than 0.2 mm in greatest dimension identified by H&E staining on final pathology (for cases where intra-operative evaluation was not performed, or was negative and complete dissection was not performed).
  • Among the minimum of 2 and the maximum of 6 sentinel nodes identified and excised by the surgeon, no more than 8 lymph nodes (sentinel and non-sentinel) were found by the pathologists to have been actually excised. 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01901094

  Show 202 Study Locations
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
Investigators
Study Chair: Judy Boughey, M.D. Mayo Clinic
  More Information

No publications provided

Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT01901094     History of Changes
Other Study ID Numbers: A011202, U10CA031946, NCI-2013-00875
Study First Received: July 12, 2013
Last Updated: June 25, 2014
Health Authority: United States: NCI Central Institutional Review Board

Additional relevant MeSH terms:
Breast Neoplasms
Lymphedema
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Lymphatic Diseases

ClinicalTrials.gov processed this record on July 20, 2014