Sentinel Lymph Node After Neoadjuvant Chemotherapy in Breast Carcinoma (GANEA3)

Sentinel lymph node dissection (SLND) after NAC, aimed to reduce the rate of unnecessary axillary lymphadenectomy, is not a standard of care in case of patient with previously involved node before NAC because of a too high false negative rate (FNR).

Clinical consequences of FNR of SLND after NAC are currently unknown. Consequently, contrary to adjuvant setting, a risk of SLND false negative case after NAC is not acceptable.

GANEA3 aims to evaluate the results of an innovative multiparametric strategy combining (1) an identification before chemotherapy of a lymph node involvement using a metal clip and then its analysis after treatment, (2) the analysis of sentinel lymph node (SLN) after NAC, and (3) analysis of biological parameters of breast tumor before and after NAC, to predict axillary status after NAC. This will identify patients with initial lymph node involvement who could benefit from SLN after NAC without additional axillary dissection with a very low FNR (≤1%).

The most "pathological" metastatic lymph node will be identified with a metal clip under ultrasound. They will then receive a NAC before breast and axillary surgery. An assessment of the NAC response at the breast and axillary will be performed by imagery. Then, all patients undergo the resection of the tagged axillary node with the metal clip, SLN detection and biopsy and a complementary axillary lymphadenectomy.

Study Overview

• Status: Recruiting
• Conditions: Invasive Breast Cancer; Axillary Metastases
• Intervention / Treatment: Procedure: Tagged axillary metastatic node

Detailed Description

GANEA3 is a prospective multicenter diagnostic study assessing the benefit of targeting initial involved node in complement to SLND and breast tumor characteristics to predict axillary status after NAC.

The diagnostic performances of this strategy will be primarily assessed by the decrease of the FNR with the combined strategy compared to SLND alone.

The primary objective is to evaluate the interest of identifying, before NAC, the initial involved lymph node to improve the prediction of axillary status after NAC.

The main secondary objectives are :

• To assess the feasibility, at the time of the surgery, of the identification and resection of the initially involved lymph node, tagged with the metal clip before NAC ;
• To evaluate the complications related to the setting up of the metal clip for the identification of a lymph node metastatic ;
• To evaluate the interest and impact of immunohistochemical analysis of tagged lymph node and SLN ;

Patients treated for a large early breast cancer (BC) needing NAC undergo axillary sonography assessment routinely performed to seek suspicious nodes. When several suspicious nodes are found only the worst is chosen. A fine needle aspiration is performed to allow cytological examination (biopsy is optional) of the suspicious node. In case of proven axillary involvement, the patient is informed about GANEA 3 study in order to be included.

At this step the patient must accept the study and sign the consent form. The involved node is then tagged (with a metal clip) under sonography. In case of multiple suspicious nodes, the radiologist must choose the worst node in order to tag only one involved node.

Then, then patients will perform their chemotherapy. The choice of NAC regimen is let at the discretion of each participating team.

After NAC, breast tumor size and axillary assessment are performed.

Breast and axillary surgery are performed during the same procedure, 4 to 6 weeks after completion of NAC. Breast surgery can be conservative or radical.

All patients undergo the resection of the tagged axillary node, SLN biopsy and a complementary axillary lymphadenectomy.

• Study Type: Interventional
• Enrollment (Anticipated): 385
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: JEAN-MARC CLASSE, MD; Phone Number: +33240679910; Email: Jean-Marc.Classe@ico.unicancer.fr

Study Locations

• France
  • Angers, France, 49055
    • Suspended
    • ICO - Site ANGERS
  • Bordeaux, France, 33076
    • Suspended
    • Institut Bergonie
  • Brest, France, 29609
    • Suspended
    • CHU Brest
  • Clermont-Ferrand, France, 63011
    • Recruiting
    • Centre Jean Perrin
    • Contact: Pierre GUIMBERGUES, MD; Email: pierre.gimbergues@cjp.fr
    • Principal Investigator: Pierre GIMBERGUES, MD
  • Dijon, France, 21079
    • Recruiting
    • Centre Georges Francoise Leclerc
    • Principal Investigator: Clémentine JANKOWSKI, MD
    • Contact: Clémentine JANKOWSKI, MD; Email: cjankowski@cgfl.fr
  • Lille, France
    • Suspended
    • Oscar Lambret
  • Lyon, France, 69373
    • Recruiting
    • Centre Leon Berard
    • Principal Investigator: Christelle FAURE, MD
    • Contact: Centre L Bérard, MD; Email: christelle.faure@lyon.unicancer.fr
  • Marseille, France, 13009
    • Recruiting
    • Institut Paoli Calmettes
    • Contact: Monique COHEN, MD; Email: cohenm@ipc.unicancer.fr
    • Principal Investigator: Monique COHEN, MD
  • Montpellier, France, 34298
    • Recruiting
    • Institut de Cancérologie de Montpellier
    • Contact: GUTOWSKI Marian, MD; Email: marian.gutowski@icm.unicancer.fr
    • Principal Investigator: Marian GUTOWSKI, MD
  • Paris, France, 75013
    • Suspended
    • Aphp - Pitie Salpetriere
  • Paris, France, 75014
    • Suspended
    • Hôpital St Joseph
  • Paris, France, 75908
    • Suspended
    • Anne-Sophie Georges BATS
  • Reims, France, 51726
    • Suspended
    • Centre Jean Godinot
  • Saint Herblain, France, 44805
    • Recruiting
    • Céline RENAUDEAU
    • Contact: Céline RENAUDEAU, MD; Phone Number: +33240679900; Email: celine.renaudeau@ico.unicancer.fr
    • Principal Investigator: Céline RENAUDEAU, MD
  • Saint-Cloud, France, 92210
    • Recruiting
    • CURIE
    • Contact: Eugénie GUILLOT; Email: eugenie.guillot@curie.fr
    • Principal Investigator: Eugénie GUILLOT, MD
  • Saint-Grégoire, France, 35760
    • Suspended
    • CHP St Grégoire
  • Toulouse, France, 31059
    • Suspended
    • IUCT-O
  • Vandœuvre-lès-Nancy, France, 54511
    • Recruiting
    • Institut de Cancérlogie de Lorraine
    • Contact: Philippe RAUCH, MD; Email: p.rauch@nancy.unicancer.fr
    • Principal Investigator: Philippe RAUCH, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Patients ≥ 18 years old
2. Initial diagnosis of operable invasive breast carcinoma
3. Histologically proven axillary metastasis (cytology or biopsy) before NAC
4. Patient included in a therapeutic approach of neoadjuvant chemotherapy
5. Procedure for the detection of sentinel lymph node by isotopic method +/- colorimetric
6. Information of the patient and obtaining written consent, signed by the patient and the investigator
7. Affiliated patient or beneficiary of the social security

Exclusion Criteria:

1. pT4d (inflammatory breast cancer)
2. Metastatic breast cancer
3. Any prior chemotherapy for contralateral breast cancer
4. Local relapse of breast cancer
5. Axillary metastasis not histologically proven before NAC
6. Allergy known to the 2 detection products (Blue and radioactive tracer)
7. Pregnant or lactating woman
8. Neo Adjuvant chemotherapy contraindicated
9. Patient protected or under guardianship or unable to give consent
10. Impossibility of submitting to the medical examination for geographical, social or psychological

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Tagged axillary metastatic node; Patients undergo axillary sonography assessment routinely performed to seek suspicious nodes. A cytological examination (biopsy is optional) of the suspicious node is performed. The involved node is then tagged with a metal clip under sonography. Then, patients receive NAC before surgery. Breast surgery (conservative or radical) and axillary surgery are performed during the same procedure, 4 to 6 weeks after completion of NAC.

Procedure: Tagged axillary metastatic node; First, initially metastatic lymph node is tagged with a metal clip under sonography. Then, patients receive NAC before surgery. Breast surgery (conservative or radical) and axillary surgery are performed during the same procedure, 4 to 6 weeks after completion of NAC. SLN isotope detection is performed with or without blue dye. All patients undergo the resection of the tagged axillary node, SLN biopsy and a complementary axillary lymphadenectomy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
False negative rate	number of cases of false prediction of absence of lymph node involvement to the total number of cases with metastatic lymph node. The rate of FN will be calculated for the involved lymph node tagged with the metal clip, the sentinel node, and the both	30 days after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification rate of involved lymph node tagged	number of cases where the tagged lymph node with a metal clip node is identified during axillary surgery and analyzed in pathology on the total number of procedures	30 days after surgery
Resection rate of involved lymph node tagged	number of cases where the tagged lymph node is resected during axillary surgery and analyzed in pathology on the total number of procedures	30 days after surgery
Complication rate	number of complications related to the axillary lymph node tagging procedure on the total number of procedures	30 days after surgery

Collaborators and Investigators

• Sponsor: Institut Cancerologie de l'Ouest
• Collaborators: Direction Générale de l'Offre de Soins
• Investigators: Study Director: JEAN-MARC CLASSE, MD, ICO Nantes

Publications and helpful links

General Publications

• Ditsch N, Rubio IT, Gasparri ML, de Boniface J, Kuehn T. Breast and axillary surgery in malignant breast disease: a review focused on literature of 2018 and 2019. Curr Opin Obstet Gynecol. 2020 Feb;32(1):91-99. doi: 10.1097/GCO.0000000000000593.

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2019
• Primary Completion (Anticipated): October 1, 2023
• Study Completion (Anticipated): October 1, 2023

Study Registration Dates

• First Submitted: August 10, 2018
• First Submitted That Met QC Criteria: August 10, 2018
• First Posted (Actual): August 15, 2018

Study Record Updates

• Last Update Posted (Actual): April 22, 2022
• Last Update Submitted That Met QC Criteria: April 21, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Neoadjuvant chemotherapy; Sentinel lymph node; Axillary lymphadenectomy; Tagged axillary metastatic node
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: ICO-N-2018-03

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No