Surgery to Remove the Sentinel Lymph Node and Axillary Lymph Nodes After Chemotherapy in Treating Women With Stage II, Stage IIIA, or Stage IIIB Breast Cancer

• ClinicalTrials.gov Identifier: NCT00881361
• Recruitment Status: Active, not recruiting
• First Posted: April 15, 2009
• Results First Posted: December 5, 2018
• Last Update Posted: August 7, 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: April 14, 2009
• First Posted Date: April 15, 2009
• Results First Submitted Date: September 19, 2018
• Results First Posted Date: December 5, 2018
• Last Update Posted Date: August 7, 2020
• Actual Study Start Date: July 2009
• Actual Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 9, 2018)

False Negative Rate (FNR) for Sentinel Lymph Node (SLN) Surgery After Chemotherapy When at Least 2 SLNs Were Excised in Women Initially Presenting With Biopsy-proven cN1 Breast Cancer [cN1 Cohort] [ Time Frame: At time of surgery ]

False negative rate (FNR) (percentage) for sentinel lymph node (SLN) surgery after chemotherapy when at least 2 SLNs were excised in women initially presenting with biopsy-proven cN1 breast cancer, defined as the number of patients with no positive lymph nodes by SLN and with at least one positive lymph node by axillary lymph node dissection (ALND) divided by the total number of patients initially presenting with biopsy-proven cN1 breast cancer with at least one positive lymph node by SLN or ALND multiplied by 100. A 2-sided Bayesian credible interval (BCI) for the true FNR was constructed.

• Original Primary Outcome Measures (submitted: April 14, 2009): False negative rate defined as number of patients with no positive lymph nodes after SLN surgery and ≥ 1 positive lymph node by axillary lymph node dissection (ALND) divided by number of patients with ≥ 1 positive lymph node by ALND

Current Secondary Outcome Measures (submitted: November 9, 2018)

• False Negative Rate (FNR) for Sentinel Lymph Node (SLN) Surgery After Chemotherapy When at Least 2 SLNs Were Excised in Women Initially Presenting With Biopsy-proven cN2 Breast Cancer [cN2 Cohort] [ Time Frame: At time of surgery ]
  False negative rate (FNR) (percentage) for sentinel lymph node (SLN) surgery after chemotherapy when at least 2 SLNs were excised in women initially presenting with biopsy-proven cN2 breast cancer, defined as the number of patients with no positive lymph nodes by SLN and with at least one positive lymph node by axillary lymph node dissection (ALND) divided by the total number of patients initially presenting with biopsy-proven cN1 breast cancer with at least one positive lymph node by SLN or ALND multiplied by 100. An interval estimate of the SLN false negative rate will be constructed using the Duffy-Santner approach.
• False-negative Rate (FNR) Under the Selection Process by Axillary Ultrasound (AUS) Status After Completion of Neoadjuvant Chemotherapy (NAC) [ Time Frame: At the time of surgery ]
  False negative rate (FNR) (percentage) for sentinel lymph node (SLN) surgery after chemotherapy in women with normal AUS and at least 2 SLNs were excised, defined as the number of patients with no positive lymph nodes by SLN and with at least one positive lymph node by axillary lymph node dissection (ALND) divided by the total number of patients with at least one positive lymph node by SLN or ALND multiplied by 100.
• Node Status After Preoperative Chemotherapy, as Measured by the Total Number of Positive Nodes (SLN+ALND) [ Time Frame: At time of surgery ]
  Node status of patients after preoperative chemotherapy, as measured by the total number of positive nodes (SLN+ALND). Patients will be classified as node positive if they were determined to have at least one positive lymph node by SLN or ALND.
• Pathologic Complete Nodal Response (pCR) Rate [ Time Frame: At the time of surgery ]
  Pathologic complete nodal response (pCR) rate (percentage) wherein a nodal pCR is pathologically node-negative (pN0) on the basis of SLN surgery and ALND. A 95% binomial confidence interval was constructed for the pCR rate.
• Residual Cancer Burden Class [ Time Frame: At time of surgery ]
  Residual cancer burden (RCB) is estimated from routine pathologic sections of the primary breast tumor site and the regional lymph nodes after the completion of neoadjuvant therapy. The calculated RCB index value can also be categorized as one of four RCB classes. The number of patients classified in the four RCB classes along with the number of patients missing this data by cohort are reported below. RCB of 0 represents a path complete response while increasing levels (I, then II, then III) indicate an increase in the 'amount' of residual disease remaining.

Original Secondary Outcome Measures (submitted: April 14, 2009)

• Axillary ultrasound status after completion of preoperative chemotherapy (i.e., ultrasound evidence of residual lymphadenopathy versus no evidence of lymphadenopathy)
• Node status after preoperative chemotherapy (positive status defined as ≥ 1 positive lymph node by SLN or ALND)
• Extent of residual cancer burden

• Current Other Pre-specified Outcome Measures (submitted: November 9, 2018): Disease-Free Survival [ Time Frame: Up to 10 years ]
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Surgery to Remove the Sentinel Lymph Node and Axillary Lymph Nodes After Chemotherapy in Treating Women With Stage II, Stage IIIA, or Stage IIIB Breast Cancer
• Official Title: A Phase II Study Evaluating the Role of Sentinel Lymph Node Surgery and Axillary Lymph Node Dissection Following Preoperative Chemotherapy in Women With Node Positive Breast Cancer (T1-4, N1-2, M0) at Initial Diagnosis

Brief Summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This phase II trial is studying surgery to remove the sentinel lymph node and axillary lymph nodes after chemotherapy in treating women with stage II, stage IIIA, or stage IIIB breast cancer.

Detailed Description

This is a multicenter study. Patients who plan to receive or have received neoadjuvant chemotherapy are eligible. Patients undergo examination for breast and axilla lymph adenopathy and then undergo ultrasound of the axillary nodes prior to registration to confirm eligibility and after completion of neoadjuvant chemotherapy. Within 12 weeks of completing neoadjuvant chemotherapy, patients undergo a mastectomy or lumpectomy (per surgeon discretion) including both sentinel lymph node surgery and axillary lymph node dissection. The primary and secondary objectives of the study are described below.

Primary Objective:

1. To determine the false negative rate for sentinel lymph node (SLN) surgery. Among the patients who have at least one sentinel lymph node identified and removed, false negative rate is defined as the number of patients declared to have no evidence of cancer in the SLN and are found to have at least one positive lymph node in the ALND divided by the total number of patients with at least one positive axillary lymph node by ALND.

Secondary Objectives:

1. To determine how the axillary ultrasound status of the patient upon completion of preoperative chemotherapy (evidence of residual lymphadenopathy on the ultrasound examination versus no evidence of lymphadenopathy in the ultrasound examination) affects the false negative rate of SLN and how sonographic findings correlate with residual disease on final pathology.
2. To determine the node status of patients after preoperative chemotherapy. Patients will be classified as node positive if they were determined to have at least one positive lymph node by SLN or ALND. Patients will be classified as node negative if all nodes examined by SLN and ALND were negative.
3. To determine whether the false-negative rate for SLN surgery after preoperative chemotherapy is related to the extent of residual cancer burden (RCB) overall, or separately in the breast or regional nodal basin.
4. To evaluate pathological complete response (pCR) rates (defined as no invasive disease in breast or lymph nodes) and disease-free survival (DFS) rates in node-positive patients receiving preoperative chemotherapy.

After completion of surgery, patients will visit the office for follow-up exams at 1-2 weeks then patients are followed every 6 months for 2 years, yearly for 2 years, then every other year for 6 years. The study closed to accrual and treatment on 5/29/12.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Diagnostic
• Condition: Breast Cancer

Intervention

• Drug: systemic chemotherapy
• Procedure: axillary lymph node dissection
• Procedure: neoadjuvant therapy
• Procedure: sentinel lymph node biopsy
• Procedure: therapeutic conventional surgery
• Procedure: ultrasound imaging

Study Arms

Study cohort

Patients who plan to receive or have received neoadjuvant chemotherapy are eligible. Patients undergo examination for breast and axilla lymph adenopathy and then undergo ultrasound of the axillary nodes at baseline and after completion of neoadjuvant chemotherapy. Within 12 weeks of completing neoadjuvant chemotherapy, patients undergo a mastectomy or lumpectomy (per surgeon discretion) including both sentinel lymph node surgery and axillary lymph node dissection.

Interventions:

• Drug: systemic chemotherapy
• Procedure: axillary lymph node dissection
• Procedure: neoadjuvant therapy
• Procedure: sentinel lymph node biopsy
• Procedure: therapeutic conventional surgery
• Procedure: ultrasound imaging

Publications *

• Le-Petross HT, McCall LM, Hunt K, et al.: Role of axillary ultrasound after neoadjuvant chemotherapy in women with node-positive breast cancer (T1-4, N1-2, M0) at initial diagnosis (ACOSOG Z1071). [Abstract] J Clin Oncol 30 (Suppl 15): A-1107, 2012.
• Boughey JC, Suman VJ, Mittendorf EA, Ahrendt GM, Wilke LG, Taback B, Leitch AM, Kuerer HM, Bowling M, Flippo-Morton TS, Byrd DR, Ollila DW, Julian TB, McLaughlin SA, McCall L, Symmans WF, Le-Petross HT, Haffty BG, Buchholz TA, Nelson H, Hunt KK; Alliance for Clinical Trials in Oncology. Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: the ACOSOG Z1071 (Alliance) clinical trial. JAMA. 2013 Oct 9;310(14):1455-61. doi: 10.1001/jama.2013.278932.
• Boughey JC, Ballman KV, Hunt KK, McCall LM, Mittendorf EA, Ahrendt GM, Wilke LG, Le-Petross HT. Axillary Ultrasound After Neoadjuvant Chemotherapy and Its Impact on Sentinel Lymph Node Surgery: Results From the American College of Surgeons Oncology Group Z1071 Trial (Alliance). J Clin Oncol. 2015 Oct 20;33(30):3386-93. doi: 10.1200/JCO.2014.57.8401. Epub 2015 Feb 2.
• Armer JM, Ballman KV, McCall L, Armer NC, Sun Y, Udmuangpia T, Hunt KK, Mittendorf EA, Byrd DR, Julian TB, Boughey JC. Lymphedema symptoms and limb measurement changes in breast cancer survivors treated with neoadjuvant chemotherapy and axillary dissection: results of American College of Surgeons Oncology Group (ACOSOG) Z1071 (Alliance) substudy. Support Care Cancer. 2019 Feb;27(2):495-503. doi: 10.1007/s00520-018-4334-7. Epub 2018 Jul 6.
• Boughey JC, Ballman KV, McCall LM, Mittendorf EA, Symmans WF, Julian TB, Byrd D, Hunt KK. Tumor Biology and Response to Chemotherapy Impact Breast Cancer-specific Survival in Node-positive Breast Cancer Patients Treated With Neoadjuvant Chemotherapy: Long-term Follow-up From ACOSOG Z1071 (Alliance). Ann Surg. 2017 Oct;266(4):667-676. doi: 10.1097/SLA.0000000000002373.
• Boughey JC, Suman VJ, Mittendorf EA, Ahrendt GM, Wilke LG, Taback B, Leitch AM, Flippo-Morton TS, Kuerer HM, Bowling M, Hunt KK; Alliance for Clinical Trials in Oncology. Factors affecting sentinel lymph node identification rate after neoadjuvant chemotherapy for breast cancer patients enrolled in ACOSOG Z1071 (Alliance). Ann Surg. 2015 Mar;261(3):547-52. doi: 10.1097/SLA.0000000000000551.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: August 3, 2015): 756
• Original Estimated Enrollment (submitted: April 14, 2009): 550
• Study Completion Date: Not Provided
• Actual Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria

Eligibility Criteria:

1. ≥ 18 years old
2. ECOG/Zubrod Performance Status 0-1
3. Female. Note: Men are excluded from this study because the number of men with breast cancer is insufficient to provide a statistical basis for assessment of effects in this subpopulation of people with breast cancer.
4. Histologic diagnosis of invasive breast cancer, clinical stage T0-4 N1-2 M0 (excluding inflammatory breast cancer).
5. FNA biopsy or core needle biopsy of an axillary node documenting nodal disease at time of diagnosis and prior to preoperative chemotherapy.
6. Preoperative chemotherapy must be completed or planned for patient. NOTE: Patients enrolling on studies involving preoperative chemotherapy (through cooperative groups or institutional studies) may be eligible for this study, provided sentinel node surgery prior to preoperative chemotherapy was not required in the other studies.
7. No prior ipsilateral axillary surgery, such as excisional biopsy of lymph node(s) or treatment of hidradenitis.
8. No prior SLN surgery/excisional lymph node biopsy for pathological confirmation of axillary status.

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: United States

Administrative Information

• NCT Number: NCT00881361
• Other Study ID Numbers: ACOSOG-Z1071; ACOSOG-Z1071; CDR0000640100 ( Registry Identifier: NCI Physician Data Query )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Alliance for Clinical Trials in Oncology
• Study Sponsor: Alliance for Clinical Trials in Oncology
• Collaborators: National Cancer Institute (NCI)

Investigators

• Study Chair: Judy Boughey, MD; Mayo Clinic

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