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

NCT01901094

Description:

This randomized phase III trial studies axillary lymph node dissection to see how well it works compared to axillary radiation therapy in treating patients with node-positive breast cancer 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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Comparison of Axillary Lymph Node Dissection With Axillary Radiation for Patients With Node-Positive Breast Cancer Treated With Chemotherapy
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: A011202
  • SECONDARY ID: U10CA031946
  • SECONDARY ID: NCI-2013-00875
  • NCT ID: NCT01901094

Conditions

  • Stage II Breast Cancer
  • Stage IIIA Breast Cancer

Purpose

This randomized phase III trial studies axillary lymph node dissection to see how well it works compared to axillary radiation therapy in treating patients with node-positive breast cancer 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.

Detailed Description

      Study Outline:

        -  All patients will undergo surgery to identify sentinel lymph node(s). If a lymph node
           (sentinel or non-sentinel) 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 node status is cannot be/is not determined intra-
           operatively, and have not undergone ALND, but had at least one lymph node (sentinel or
           non-sentinel) found to be positive on final pathology review will be
           registered/randomized post-operatively.

        -  Patients whose sentinel lymph node status is found to be negative intra-operatively and
           have not undergone ALND, but had at least one lymph node (sentinel or non-sentinel)
           found to be positive on final pathology review will be registered/randomized
           post-operatively.

        -  ALND is not to be performed prior to registration/randomization.

        -  Patients who are determined to have negative lymph nodes on final pathology will not be
           registered/randomized, but can be offered participation in another cooperative group
           trial.

      The primary and secondary objectives of the study are described below. Please see the "Arms"
      section for a detailed description of the treatment regimens.

      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 for each
           treatment arm

        -  To estimate the distribution of overall survival for each treatment arm

      Patients may receive adjuvant and ancillary therapy as appropriate per the protocol.

      Adjuvant Therapy:

        -  Adjuvant endocrine therapy: 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 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.

      Ancillary Therapy:

        -  Patients should receive full supportive care, including transfusions of blood and blood
           products, erythropoetin (unless otherwise specified in the protocol), antibiotics,
           antiemetics, etc. when appropriate.

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

Trial Arms

NameTypeDescriptionInterventions
Arm 1: ALND + nodal radiation therapyOtherSurgery: 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.
    Arm 2: Axillary radiation and nodal radiation therapyOtherRadiation 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.

      Eligibility Criteria

              Pre-Registration Eligibility Criteria:
      
                1. Patients ≥ 18 years of age
      
                2. 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
      
                3. No inflammatory breast cancer
      
                4. 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
      
                5. 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.
      
                6. Patients must have had estrogen receptor, progesterone receptor and human epidermal
                   growth factor receptor 2 (HER2) status by immunohistochemistry [IHC] and/or
                   fluorescence in situ hybridization [FISH] evaluated on diagnostic core biopsy prior to
                   start of neoadjuvant chemotherapy. Note: If HER2 status has not been clearly
                   determined (ie equivocal/indeterminate), then patients should not be enrolled.
      
                7. 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 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 NAC may be administered at the
                   discretion of the treating medical oncologist.
      
                8. 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.
      
                9. 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. NOTE: An ultrasound of the axilla is not required at completion of
                   neoadjuvant chemotherapy. If performed, its findings do NOT impact eligibility.
      
               10. No neoadjuvant endocrine therapy
      
               11. No neoadjuvant radiation therapy
      
               12. No sentinel lymph node (SLN) surgery/excisional biopsy for pathological confirmation
                   of axillary status prior to or during neoadjuvant chemotherapy
      
               13. 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.
      
               14. No prior ipsilateral axillary surgery, such as excisional biopsy of lymph node(s) or
                   treatment of hidradenitis.
      
               15. No history of prior or concurrent contralateral invasive breast cancer. Benign breast
                   disease, LCIS or DCIS of contralateral breast is allowed.
      
               16. 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.
      
               17. Eastern Cooperative Oncology Group (ECOG) (Zubrod) performance status 0-1.
      
               18. Required Pre-Registration Laboratory Values:
      
                     -  Serum or urine beta-human chorionic gonadotropin (ß-HCG)
      
                     -  Negative in women of child-bearing potential
      
              Intra-Operative Registration/Randomization Criteria:
      
                1. Breast surgery (lumpectomy or mastectomy) and sentinel lymph node surgery must be
                   completed within 56 days of the completion of neoadjuvant chemotherapy.
      
                2. A minimum of 1 sentinel node and a maximum of 6 total nodes (sentinel + non-sentinel)
                   are identified and excised by the surgeon. Patients who do not have an identifiable
                   sentinel lymph node will not proceed to Registration/Randomization.
      
                3. At least one lymph node (sentinel or non-sentinel) 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:
      
              1. For cases where ALND has not been performed and one of the following is true:
      
                -  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 on hematoxylin and eosin stain (H & E) OR
      
                -  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 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 (sentinel or non-sentinel) 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
                        completion dissection was not performed).
      
                     -  Among the minimum of 1 and the maximum of 6 nodes (sentinel or non-sentinel)
                        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.
            
      Maximum Eligible Age:N/A
      Minimum Eligible Age:18 Years
      Eligible Gender:All
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:Invasive breast cancer recurrence-free interval (IBC-RFI)
      Time Frame:Up to 5 years after completion of radiation therapy
      Safety Issue:
      Description:

      Secondary Outcome Measures

      Measure:Overall survival
      Time Frame:Up to 5 years after completion of radiation therapy
      Safety Issue:
      Description:
      Measure:Ipsilateral/local/regional invasive breast cancer recurrence (ILR-REC)
      Time Frame:Up to 5 years after completion of radiation therapy
      Safety Issue:
      Description:

      Details

      Phase:Phase 3
      Primary Purpose:Interventional
      Overall Status:Recruiting
      Lead Sponsor:Alliance for Clinical Trials in Oncology

      Last Updated

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