Lymph Node Removal in Treating Women Who Have Stage I or Stage IIA Breast Cancer

• ClinicalTrials.gov Identifier: NCT00003855
• Recruitment Status: Completed
• First Posted: January 27, 2003
• Last Update Posted: April 29, 2020
• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Alliance for Clinical Trials in Oncology

Tracking Information

• First Submitted Date: November 1, 1999
• First Posted Date: January 27, 2003
• Last Update Posted Date: April 29, 2020
• Study Start Date: April 1999
• Actual Primary Completion Date: August 2007 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 6, 2015)

• Overall survival [ Time Frame: Up to 10 years ]
• Morbidity [ Time Frame: Up to 10 years ]
• Disease-free survival [ Time Frame: Up to 10 years ]

• Original Primary Outcome Measures: Not Provided
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Lymph Node Removal in Treating Women Who Have Stage I or Stage IIA Breast Cancer
• Official Title: A Randomized Trial of Axillary Node Dissection in Women With Clinical T1-2 N0-1 M0 Breast Cancer Who Have a Positive Sentinel Node

Brief Summary

RATIONALE: Surgery to remove lymph nodes in the armpit may remove cancer cells that have spread from tumors in the breast.

PURPOSE: Randomized phase III trial to determine the effectiveness of removing lymph nodes in the armpit in treating women who have stage I or stage IIA breast cancer.

Detailed Description

OBJECTIVES:

Primary objectives:

Long term: To assess whether overall survival for patients randomized to Arm 2 (no immediate ALND) is essentially equivalent to (or better than) than that for patients assigned to Arm 1 (completion ALND).

Short term: To quantify and compare the surgical morbidities associated with SLND plus ALND versus SLND alone.

OUTLINE: This is a randomized study. After segmental mastectomy and sentinel lymph node dissection, patients are stratified according to age (50 and under vs over 50), estrogen receptor status (positive vs negative), and tumor size (no greater than 1 cm vs greater than 1 cm but no greater than 2 cm vs greater than 2 cm). Patients are randomized to one of two treatment arms.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Breast Cancer

Intervention

• Procedure: axillary lymph node dissection
• Radiation: whole breast irradiation

Study Arms

• Experimental: Surgery + radiotherapy

  Patients undergo axillary lymph node dissection involving removal of at least level I and II nodes, followed by whole-breast radiotherapy (exclusive of a third supraclavicular field) 5 days a week for a maximum of 7 weeks. Patients may receive adjuvant systemic therapy at the discretion of the treating physician.

  Patients are followed up at 30 days, at 6, 12, 18, 30, and 36 months, and then annually for a total of 10 years.

  Interventions:

  • Procedure: axillary lymph node dissection
  • Radiation: whole breast irradiation
• Active Comparator: Radiotherapy

  Patients undergo breast radiotherapy only. Patients may receive adjuvant systemic therapy at the discretion of the treating physician.

  Patients are followed up at 30 days, at 6, 12, 18, 30, and 36 months, and then annually for a total of 10 years.

  Intervention: Radiation: whole breast irradiation

Publications *

• Ainsworth RK, Kollias J, Le Blanc A, De Silva P. The clinical impact of the American College of Surgeons Oncology Group Z-0011 trial--results from the BreastSurgANZ National Breast Cancer Audit. Breast. 2013 Oct;22(5):733-5. doi: 10.1016/j.breast.2012.11.005. Epub 2013 Jan 2.
• Gainer SM, Hunt KK, Beitsch P, Caudle AS, Mittendorf EA, Lucci A. Changing behavior in clinical practice in response to the ACOSOG Z0011 trial: a survey of the American Society of Breast Surgeons. Ann Surg Oncol. 2012 Oct;19(10):3152-8. doi: 10.1245/s10434-012-2523-z. Epub 2012 Jul 21.
• Olson JA Jr, McCall LM, Beitsch P, Whitworth PW, Reintgen DS, Blumencranz PW, Leitch AM, Saha S, Hunt KK, Giuliano AE; American College of Surgeons Oncology Group Trials Z0010 and Z0011. Impact of immediate versus delayed axillary node dissection on surgical outcomes in breast cancer patients with positive sentinel nodes: results from American College of Surgeons Oncology Group Trials Z0010 and Z0011. J Clin Oncol. 2008 Jul 20;26(21):3530-5. doi: 10.1200/JCO.2007.15.5630.
• Leitch AM, McCall L, Beitsch P, et al.: Factors influencing accrual to ACOSOG Z0011, a randomized phase III trial of axillary dissection vs. observation for sentinel node positive breast cancer. [Abstract] J Clin Oncol 24 (Suppl 18): A-601, 2006.
• Krishnan MS, Recht A, Bellon JR, Punglia RS. Trade-offs associated with axillary lymph node dissection with breast irradiation versus breast irradiation alone in patients with a positive sentinel node in relation to the risk of non-sentinel node involvement: implications of ACOSOG Z0011. Breast Cancer Res Treat. 2013 Feb;138(1):205-13. doi: 10.1007/s10549-013-2418-0. Epub 2013 Jan 22.
• Shah-Khan M, Boughey JC. Evolution of axillary nodal staging in breast cancer: clinical implications of the ACOSOG Z0011 trial. Cancer Control. 2012 Oct;19(4):267-76. doi: 10.1177/107327481201900403.
• Caudle AS, Hunt KK, Kuerer HM, Meric-Bernstam F, Lucci A, Bedrosian I, Babiera GV, Hwang RF, Ross MI, Feig BW, Hoffman K, Litton JK, Sahin AA, Yang W, Hortobagyi GN, Buchholz TA, Mittendorf EA. Multidisciplinary considerations in the implementation of the findings from the American College of Surgeons Oncology Group (ACOSOG) Z0011 study: a practice-changing trial. Ann Surg Oncol. 2011 Sep;18(9):2407-12. doi: 10.1245/s10434-011-1593-7. No abstract available.
• Giuliano AE, Hunt KK, Ballman KV, Beitsch PD, Whitworth PW, Blumencranz PW, Leitch AM, Saha S, McCall LM, Morrow M. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. JAMA. 2011 Feb 9;305(6):569-75. doi: 10.1001/jama.2011.90.
• Giuliano AE, McCall L, Beitsch P, Whitworth PW, Blumencranz P, Leitch AM, Saha S, Hunt KK, Morrow M, Ballman K. Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastases: the American College of Surgeons Oncology Group Z0011 randomized trial. Ann Surg. 2010 Sep;252(3):426-32; discussion 432-3. doi: 10.1097/SLA.0b013e3181f08f32.
• Lucci A, McCall LM, Beitsch PD, Whitworth PW, Reintgen DS, Blumencranz PW, Leitch AM, Saha S, Hunt KK, Giuliano AE; American College of Surgeons Oncology Group. Surgical complications associated with sentinel lymph node dissection (SLND) plus axillary lymph node dissection compared with SLND alone in the American College of Surgeons Oncology Group Trial Z0011. J Clin Oncol. 2007 Aug 20;25(24):3657-63. doi: 10.1200/JCO.2006.07.4062. Epub 2007 May 7.
• Giuliano AE, Ballman KV, McCall L, Beitsch PD, Brennan MB, Kelemen PR, Ollila DW, Hansen NM, Whitworth PW, Blumencranz PW, Leitch AM, Saha S, Hunt KK, Morrow M. Effect of Axillary Dissection vs No Axillary Dissection on 10-Year Overall Survival Among Women With Invasive Breast Cancer and Sentinel Node Metastasis: The ACOSOG Z0011 (Alliance) Randomized Clinical Trial. JAMA. 2017 Sep 12;318(10):918-926. doi: 10.1001/jama.2017.11470.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 6, 2015): 605
• Original Enrollment: Not Provided
• Actual Study Completion Date: February 2011
• Actual Primary Completion Date: August 2007 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

PLEASE NOTE: Patients registered to this study may undergo intra-operative or post¬operative randomization.

1. Patient must be female.
2. Patient must be at least 18 years of age.
3. Patient's clinical stage must be documented as tumor size less than 5 cm, with no palpable nodes and no evidence of metastatic disease (T1 or T2 N0 M0; see appendices for staging criteria) and the tumor documented as amenable to lumpectomy.
4. Patient must have a tissue diagnosis of invasive breast carcinoma. Note: A patient can be registered to this study if they have a cytologic diagnosis suggestive of carcinoma from a fine needle aspiration (FNA) of a palpable or non-palpable breast lesion and the investigator believes the breast lesion is clinically suspicious for invasive breast carcinoma.
5. Date of the patient's first tissue diagnosis of invasive breast carcinoma or cytologic diagnosis of carcinoma must be no more than 60 days prior to the SLND.
6. The patient who had BCT (segmental mastectomy) performed previously, and is now referred to the local investigator for SLND, is eligible if the BCT was less than or equal to 60 days prior to the SLND. NOTE: Copies of the operative and pathology reports must be submitted as part of the registration process.
7. Patient must have ECOG/Zubrod status =2, as documented in patient's medical record.
8. Patient must be available for follow-up.
9. Patient of childbearing potential must have a negative serum or urine pregnancy test within 14 days of beginning study interventions.
10. Patient must have access to radiation therapy.

11. A sentinel lymph node must be identified that contains metastatic breast cancer as documented by frozen section, touch prep, or H&E staining on permanent section.

    • NOTE: Patients with metastatic breast cancer identified by immunohistochemistry (IHC) are not eligible.
12. Patient randomized to ALND must undergo ALND within 42 days of their SLND.

13. A patient with a history of a previous malignancy is eligible for this study as long as the patient meets the following criteria for a cancer survivor. A cancer survivor is eligible provided that the following criteria are met:

    1. The patient has undergone potentially curative therapy for all prior malignancies,
    2. There has been no evidence of any prior malignancies for at least five years with no evidence of recurrence (except for effectively treated basal cell or squamous carcinoma of the skin, carcinoma in -situ of the cervix that has been effectively treated by surgery alone, or lobular carcinoma in-situ of the ipsilateral or contralateral breast treated by surgery alone), and
    3. The patient is deemed by their treating physician to be at low risk for recurrence from prior malignancies.
14. Patient or the patient's legally acceptable representative must provide a signed and dated written informed consent prior to registration and any study-related procedures.
15. Patient must provide written authorization to allow the use and disclosure of their protected health information. NOTE: This may be obtained in either the study-specific informed consent or in a separate authorization form and must be obtained from the patient prior to study registration.

Exclusion Criteria:

1. Patient is lactating (breastfeeding).
2. Patient has been previously treated with chemotherapy, estrogen receptor antagonists (i.e., Tamoxifen) or selective estrogen receptor modulators (SERMs, i.e., Raloxifene) for this invasive breast cancer.
3. Patient has a previously placed pre-pectoral breast implant. NOTE: A subpectoral implant is allowed.
4. Patient has concurrent invasive bilateral breast malignancies.
5. Patient has clinically and radiologically identified multi-centric disease that is not amenable to a single lumpectomy.
6. Patient has had previous ipsilateral axillary surgery such as excisional biopsy of lymph node(s), treatment of hidradenitis.
7. Patient has a medical contraindication to ALND or is considered a poor surgical risk due to a non-malignant systemic disease (cardiovascular, renal, etc.) that would preclude the treatment options.
8. Patient who is noted to have matted nodes or gross extranodal disease at the time of SLND.
9. Patient has three or more positive sentinel nodes by frozen section, touch prep, or H&E staining on permanent section.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Canada, Ireland, United States

Administrative Information

• NCT Number: NCT00003855
• Other Study ID Numbers: ACOSOG-Z0011; GUMC-00153; CDR0000067018 ( Registry Identifier: NCI Physician Data Query )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Alliance for Clinical Trials in Oncology
• Original Responsible Party: Not Provided
• Current Study Sponsor: Alliance for Clinical Trials in Oncology
• Original Study Sponsor: American College of Surgeons
• Collaborators: National Cancer Institute (NCI)

Investigators

• Study Chair: Armando E. Giuliano, MD; Saint John's Cancer Institute

• PRS Account: Alliance for Clinical Trials in Oncology
• Verification Date: April 2020