Axillary Lymph Node Dissection Versus no Dissection in Breast Cancer With Positive Sentinel Lymph Node (Z0011-China)

A Prospective Randomized Multicenter Phase III Study of Axillary Lymph Node Dissection Versus no Dissection in Breast Cancer With Positive Sentinel Lymph Node--the Validation of Z0011 in China

The recently randomized trial (ASCOG Z0011) support that among patients with limited sentinel lymph node (SLN) metastatic breast cancer treated with breast conservation and systemic therapy, the use of sentinel lymph node biopsy (SLNB) alone compared with axillary lymph node dissection (ALND) did not result in inferior survival. These patients, therefore, are unlikely to benefit from further surgery that results in a longer period of hospitalization, higher costs and higher postoperative morbidity. This result has been written in the 2012 National Comprehensive Cancer Network Clinical Practice Guidelines.

However, Limitations of Z0011, such as failure to achieve target accrual and possible randomization imbalance favoring the SLNB-alone group, must be considered. In the other hand, further testing in different country are needed.

The investigators design and begin a prospective randomized multicenter phase III study of ALND vs. no ALND in breast Cancer with positive SLN--the validation of Z0011 in China.

Study Overview

• Status: Withdrawn
• Conditions: Breast Cancer
• Intervention / Treatment: Procedure: Sentinel Lymph Node Biopsy; Procedure: Intraoperative Pathological Examination; Procedure: Axillary Lymph Node Dissection; Procedure: Pathological Evaluation; Drug: Adjuvant Systemic Therapy; Radiation: Radiation Therapy

Detailed Description

OBJECTIVES:

To determine the effects of complete axillary lymph node dissection (ALND) on survival of patients with sentinel lymph node (SLN) metastasis of breast cancer.

OUTLINE: This is a randomized multicenter study. Before randomization, all women were stratified according to age (≤50 years, >50 years), tumor size(≤2cm, >2cm) and research center. All the patients underwent lumpectomy and sentinel lymph node biopsy (SLNB). Eligible women were randomly assigned to ALND or no ALND Active Comparator: Patients undergo axillary lymph node dissection involving removal of at least level I and II nodes.

Experimental: No surgery of axillary lymph node in this arm. All the patients were to receive whole-breast opposing tangential-field radiation therapy. The use of adjuvant systemic therapy was determined by the treating physician according to the recently NCCN.

Patients are followed up every 4 months for the first 2 years, every 6 months from the third year to the fifth year, and then annually for a total of 10 years.

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China, 250117
      • Shandong Cancer Hospital and Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Female;
• Patient aged 18 years and above;
• Patient with histological proven invasive breast cancer;
• Clinical T1-T2 disease with no distant metastasis;
• Patient with clinical N0 status;
• Patient for whom conservative surgery with sentinel lymph node (SLN) technique is feasible from the start in terms of carcinologic;
• Patient with positive SLNs 1~2;
• Signed consent to participate.

Exclusion Criteria:

• History of neoadjuvant chemotherapy or hormone therapy;
• History of breast cancer (ipsilateral, i.e. recurrence, or contralateral breast);
• History of any other invasive cancer;
• Initial metastatic disease known;
• Pregnant women or lactating women;
• Impossibility to undergo medical examinations of the study for geographical, social or psychological reasons.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Axillary Lymph Node Dissection; After sentinel lymph node biopsy, surgery for standard axillary lymph node dissection. Pathological evaluation (include intraoperative pathological examination) is performed routinely. All women were to receive whole-breast opposing tangential-field radiation therapy. Adjuvant systemic therapy was determined by the treating physician.	Procedure: Sentinel Lymph Node Biopsy; Sentinel lymph nodes are identified with the combining use of intraoperative gamma detector and/or blue dye.; Other Names: SLNB; Procedure: Intraoperative Pathological Examination; touch imprint cytology and/or frozen section and/or OSNA; Procedure: Axillary Lymph Node Dissection; Axillary lymph node dissection involving removal of at least level I and II nodes.; Other Names: ALND; Procedure: Pathological Evaluation; H&E and IHC; Drug: Adjuvant Systemic Therapy; Adjuvant systemic therapy was determined by the treating physician according to the recently NCCN.; Other Names: chemotherapy or hormone therapy; Radiation: Radiation Therapy; Whole-breast opposing tangential-field radiation therapy.
Experimental: Non-Axillary Lymph Node Dissection; After sentinel lymph node biopsy, no surgery of axillary lymph node In this study, the absence of surgery is the experimental arm (non-inferiority trial). Pathological evaluation (include intraoperative pathological examination) is performed routinely. All women were to receive whole-breast opposing tangential-field radiation therapy. Adjuvant systemic therapy was determined by the treating physician.	Procedure: Sentinel Lymph Node Biopsy; Sentinel lymph nodes are identified with the combining use of intraoperative gamma detector and/or blue dye.; Other Names: SLNB; Procedure: Intraoperative Pathological Examination; touch imprint cytology and/or frozen section and/or OSNA; Procedure: Pathological Evaluation; H&E and IHC; Drug: Adjuvant Systemic Therapy; Adjuvant systemic therapy was determined by the treating physician according to the recently NCCN.; Other Names: chemotherapy or hormone therapy; Radiation: Radiation Therapy; Whole-breast opposing tangential-field radiation therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Free Survival	Time from randomization to relapse or death.	Time to relapse or progression up to 10 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Time from randomization to date of death.	Time to death up to 10 years
Axillary Recurrence Rate	Estimate the incidence of axillary recurrence after surgery followed by axillary dissection or after surgery alone.	Time to local relapse up to 10 years

Collaborators and Investigators

• Sponsor: Shandong Cancer Hospital and Institute
• Investigators: Principal Investigator: Jiong Wu, MD, Fudan University; Principal Investigator: Tao Ouyang, MD, Beijing Cancer Hospital and Institute; Principal Investigator: Feng-xi Su, MD, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University; Principal Investigator: Hong-yuan Li, MD, First Affiliated Hospital of Chongqing Medical University

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Anticipated): December 1, 2025
• Study Completion (Anticipated): June 1, 2026

Study Registration Dates

• First Submitted: February 19, 2013
• First Submitted That Met QC Criteria: February 20, 2013
• First Posted (Estimate): February 21, 2013

Study Record Updates

• Last Update Posted (Actual): April 5, 2018
• Last Update Submitted That Met QC Criteria: April 3, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: Breast Cancer; Sentinel Lymph Node Biopsy; Axillary Lymph Node Dissection
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormones
• Other Study ID Numbers: Z0011-China