Tailored Axillary Surgery With or Without Axillary Lymph Node Dissection Followed by Radiotherapy in Patients With Clinically Node-positive Breast Cancer (TAXIS)

Node-positive Breast Cancer Clinical Trial

— TAXIS  

Official title:

Tailored Axillary Surgery With or Without Axillary Lymph Node Dissection Followed by Radiotherapy in Patients With Clinically Node-positive Breast Cancer (TAXIS). A Multicenter Randomized Phase III Trial (OPBC-03/ SAKK 23/16 /IBCSG 57-18 / ABCSG-53 / GBG-101)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03513614
• Other study ID #: 2018-00838; ch20Weber2
• Secondary ID: 2018-000372-14
• Status: Recruiting
• Phase: N/A
• Start date: August 7, 2018
• Est. completion date: December 2036

Study information

• Verified date: June 2023
• Source: University Hospital, Basel, Switzerland
• Contact: Walter P. Weber, Prof.
• Phone: +41 61 328 61 49
• Email: walter.weber[@]usb.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: The use of tailored axillary dissection as a tailored procedure will avoid surgical overtreatment by selectively removing the lymph nodes that are affected by the cancer, thereby sparing many women the unnecessary complications of a radical surgery, providing a better quality of life while keeping the same efficacy.

PURPOSE: The phase III trial is evaluating the optimal treatment for breast cancer patients in terms of surgery and radiotherapy.

Description:

The removal of all lymph nodes in the armpit through conventional axillary dissection has been standard care for all patients with breast cancer for almost a century. In the nineties, the sentinel lymph node procedure, which involves the selective removal of the first few affected lymph nodes, was introduced in clinical practice. Today, conventional axillary dissection is still performed on many women with breast cancer that has spread to the nodes. It is the cause for relevant morbidity in the form of lymphedema, impairment of shoulder mobility, sensation disorders and chronic pain in as much as one third of all women undergoing the procedure.

The TAXIS trial will evaluate the optimal treatment for breast cancer patients in terms of surgery and radiotherapy. In particular, it will investigate the value of tailored axillary surgery (TAS), a new technique that aims at selectively removing the positive lymph nodes. TAS combines the removal of palpably suspicious nodes with the sentinel procedure. TAS is a promising procedure that may significantly decrease morbidity in breast cancer patients by avoiding surgical overtreatment.

This trial has the potential to establish a new worldwide treatment standard with hopefully less side effects and a better quality of life, while keeping the same efficacy as provided by radical surgery.

The main objective of the trial is to show that TAS and axillary radiotherapy (RT) is non-inferior to ALND in terms of disease-free survival of node positive breast cancer patients at high risk of recurrence in the era of effective systemic therapy and extended regional nodal irradiation.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1500
• Est. completion date: December 2036
• Est. primary completion date: December 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Inclusion criteria at pre-registration:

• Written informed consent according to ICH/GCP regulations prior to any trial specific procedures.

• Breast cancer, node positive detected by palpation or imaging (with or without planned neoadjuvant treatment)

• Female or male aged = 18 years

• Ability to complete the Quality of Life questionnaires

Inclusion criteria at registration:

• Node-positive breast cancer (histologically or cytologically proven both in primary tumor and in lymph node) AJCC/UICC [42] stage II-III (all molecular subtypes allowed):

• Node-positivity detected by imaging (iN+) and confirmed by pathology

• Node-positivity detected by palpation (cN1-3) and confirmed by pathology

• Occult breast cancer is allowed, if biopsy-proven axillary lymphatic metastasis is present

• Eligible for primary ALND or sentinel lymph node (SLN) procedure with frozen section and either:

• Newly diagnosed

• Isolated in-breast recurrence or second ipsilateral breast cancer after previous breast conserving surgery and sentinel procedure and at least 3 years disease free and no prior axillary dissection or axillary RT

• Most suspicious axillary lymph node clipped

• Baseline Quality of Life questionnaire has been completed

• WHO performance status 0-2

• Adequate condition for general anesthesia and breast cancer surgery

• Women with child-bearing potential are using effective contraception, are not pregnant or lactating and agree not to become pregnant during trial treatment and thereafter during the time recommended by the guidelines for adjuvant systemic therapies. A negative pregnancy test before inclusion into the trial is required for all women with child-bearing potential.

• Men agree not to father a child during trial treatment and thereafter during 6 months.

Inclusion criteria at randomization (intraoperatively)

• Node-positive breast cancer (histologically or cytologically proven both in primary tumor and in lymph node) AJCC/UICC stage II-III (all molecular subtypes allowed):

• Node-positivity initially detected by imaging and non-palpable and residual disease confirmed by pathology** (including residual ITCs) in SLN or non SLN in case of prior neoadjuvant treatment

• Node-positivity initially palpable and residual disease confirmed by pathology** (including residual ITCs) in case of prior neoadjuvant treatment

• Note: patients with ypN0(i+) can be included (the AJCC stage II-III refers to the stage before neoadjuvant treatment) **Note: If the fine needle aspiration or core biopsy of the clipped node after neoadjuvant treatment unequivocally shows cancer, repeated confirmation of residual disease by intraoperative frozen section is not mandatory

Exclusion Criteria:

Exclusion criteria at pre-registration:

Any potential patient who meets any of the following criteria has to be excluded from entering the trial.

• Stage IV breast cancer

• Clinical N3c breast cancer (clinical N3a and clinical N3b are allowed)

• Clinical N2b breast cancer (clinical N2a is allowed)

• Contralateral breast cancer within 3 years Note: Contralateral Ductal Carcinoma In Situ (DCIS) is allowed if prior treatment does not interfere with or compromise the trial treatment

• Prior axillary surgery (except prior sentinel node procedure in case of in- breast recurrence)

• Prior regional radiotherapy

• History of hematologic or primary solid tumor malignancy, unless in remission for at least 3 years from pre-registration with the exception of adequately treated cervical carcinoma in situ or localized non-melanoma skin cancer.

• Treatment with any experimental drug within 30 days of pre-registration

• Any other serious underlying medical, psychiatric, psychological, familial or geographical condition, which in the judgment of the investigator may interfere with the planned staging, treatment and follow-up, affect patient compliance or place the patient at high risk from treatment-related complications.

Exclusion criteria at randomization (intraoperatively):

Any potential patient who meets any of the following criteria has to be excluded from the trial.

• Absence of clip in the specimen radiography

• Palpable disease left behind in the axilla after Tailored Axillary Surgery (TAS)

• No SLN identified in the axilla

Related Conditions & MeSH terms

• Breast Neoplasms
• Node-positive Breast Cancer

Intervention

Procedure:
• Tailored axillary surgery - both Arms
Axillary lymph node dissection - Arm A

Radiation:
• Radiotherapy - Arm A
Regional nodal irradiation excluding the dissected axilla - Arm A
• Radiotherapy - Arm B
Regional nodal irradiation including the full axilla - Arm B

Locations

Country	Name	City	State
Argentina	Institute of Oncology "Angel H. Roffo	Buenos Aires
Austria	Krankenhaus Dornbirn	Dornbirn
Austria	Landeskrankenhaus Feldkirch	Feldkirch
Austria	Medical University of Innsbruck, Department of Gynecology	Innsbruck
Austria	Ordens Kinikum Linz, Barmherzige Schwestern	Linz
Austria	Universitätsklinik für Frauenheilkunde und Geburtshilfe; Landeskrankenhaus Salzburg der PMU	Salzburg
Austria	Hanusch Hospital Vienna	Vienna
Austria	Klinikum Wels-Grieskrichen GmbH	Wels
Austria	Medizinische Universität Wien - Klinik für Chirurgie	Wien
Austria	Medizinische Universität Wien - Universitätsklinik für Frauenheilkunde	Wien
Croatia	Breast Centre of Clinical Hospital	Rijeka
Germany	Ev. Waldkrankenhaus Spandau	Berlin
Germany	KEM | Evang. Kliniken Essen-Mitte gGmbH	Essen
Germany	Niels-Stensen-Kliniken Franziskus-Hospital Harderberg	Georgsmarienhütte
Germany	Universitätsklinikum Heidelberg, Sektion Senologie	Heidelberg
Germany	ViDia Christliche Kliniken Karlsruhe, Diakonissenkrankenhaus	Karlsruhe
Germany	Onkologie Rheinsieg	Troisdorf
Germany	Helios University Hospital Wuppertal	Wuppertal
Greece	Alexandra General Hospital	Athens
Greece	Attikon University Hospital	Chaidari	Athens
Greece	University Hospital of Heraklion	Heraklion	Crete
Hungary	National Institute of Oncology	Budapest
Hungary	Bacs-Kiskun Country Hospital	Kecskemet
Hungary	University of Szeged	Szeged
Italy	Ospedale MultiMedica Castellanza	Castellanza
Lithuania	National Cancer Institut	Vilnius
Switzerland	Kantonsspital Aarau	Aarau
Switzerland	Brustzentrum Basel und Netzwerk	Allschwil
Switzerland	Kantonsspital Baden	Baden
Switzerland	Bethesda Spital Basel, Gynäkologie und Geburtshilfe	Basel
Switzerland	St. Claraspital AG	Basel
Switzerland	Universitätsspital Basel	Basel
Switzerland	Brustzentrum Bern, Lindenhofgruppe Centerclinic	Bern
Switzerland	Clinique de Grangettes	Chêne-Bougeries
Switzerland	Kantonsspital Graubünden	Chur
Switzerland	Brustzentrum Thurgau	Frauenfeld
Switzerland	Breast center Fribourg	Fribourg
Switzerland	HUG - Hôpitaux Universitaires de Genève	Genève
Switzerland	Clinique de Genolier	Genolier
Switzerland	Hôpital Neuchâtelois	La Chaux-de-Fonds
Switzerland	Centre Hospitalier Universitaire Vaudois CHUV	Lausanne
Switzerland	Hirslanden Klinik St. Anna	Lucerne
Switzerland	Luzerner Kantonsspital - Brustzentrum	Luzern
Switzerland	Spital Limmattal	Schlieren
Switzerland	Hôpital du Valais / Hôpital de Sion	Sion
Switzerland	Kantonsspital St. Gallen	St. Gallen
Switzerland	Tumor-and Breast centre Ostschweiz	St. Gallen
Switzerland	Kantonsspital Winterthur, Brustzentrum	Winterthur
Switzerland	Spital Zollikerberg	Zollikerberg
Switzerland	Brust-Zentrum Zürich (Seefeld)	Zürich
Switzerland	Stadtspital Triemli	Zürich
Switzerland	Universitäts Spital Zürich	Zürich

Sponsors (3)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland	Austrian Breast Cancer Study Group, ETOP IBCSG Partners Foundation

Countries where clinical trial is conducted

Argentina,  Austria,  Croatia,  Germany,  Greece,  Hungary,  Italy,  Lithuania,  Switzerland, 

References & Publications (1)

Weber WP, Matrai Z, Hayoz S, Tausch C, Henke G, Zwahlen DR, Gruber G, Zimmermann F, Seiler S, Maddox C, Ruhstaller T, Muenst S, Ackerknecht M, Kuemmel S, Bjelic-Radisic V, Kurzeder C, Ujhelyi M, Vrieling C, Satler R, Meyer I, Becciolini C, Bucher S, Simon — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-free survival (DFS)	The primary endpoint of this trial is DFS, defined as time from randomization until one of the following events, whichever comes first: Local recurrence, regional recurrence, distant recurrence; Second breast cancer; Death from any cause Patients not experiencing an event will be censored at the date of the last available assessment.	at the occurrence of the event or latest 20 years after randomization of the last patient
Secondary	Overall survival (OS)	OS will be calculated from randomization until death from any cause. Patients not experiencing an event will be censored at the last date they were known to be alive.	at the occurrence of the event or latest 20 years after randomization of the last patient
Secondary	Breast cancer-specific survival (BCSS)	BCSS will be calculated from randomization until death from breast cancer. Patients not experiencing an event will be censored at the last date they were known to be alive.	at the occurrence of the event or latest 20 years after randomization of the last patient
Secondary	Time to local recurrence (TTLR)	TTLR will be calculated from randomization until local recurrence or death from breast cancer. Patients not experiencing an event or patients who died due to other reasons before experiencing an event will be censored at the date of the last available assessment.	at the occurrence of the event or latest 20 years after randomization of the last patient
Secondary	Time to distant recurrence (TTDR)	TTDR will be calculated from randomization until distant recurrence or death from breast cancer. Patients not experiencing an event or patients who died due to other reasons before experiencing an event will be censored at the date of the last available assessment.	at the occurrence of the event or latest 20 years after randomization of the last patient
Secondary	Physician reported morbidity outcomes (Lymphedema)		at baseline, at week 1 and 4 after surgery, before the beginning of radiotherapy. During follow-up: 9 and 12 months after randomization then every 6 months up to 3 years, then every year up to 20 years after randomization of the last patient.
Secondary	Physician reported morbidity outcomes (Decreased range of shoulder motion)		at baseline, at week 1 and 4 after surgery. During follow-up: 9 and 12 months after randomization then every 6 months up to 3 years, then every year up to 10 years after randomization of the last patient.
Secondary	Adverse events according to NCI CTCAE v4.03	Clipping-related AEs and specific AEs related to the surgical procedure and radiotherapy will be assessed according to NCI CTCAE v4.03.	from date of patient consent and up to 20 years after randomization of the last patient
Secondary	Late radiotherapy-related adverse events	Late adverse events related to the radiotherapy will be assessed according to the Late Effects in Normal Tissues-Subjective, Objective, Management and Analytic (LENT-SOMA) scale	from date of patient consent and up to 20 years after randomization of the last patient
Secondary	Surgical site infections (SSI)	SSIs will be assessed according to the Centers for Disease Control and Prevention Surgical Site Infection Classification System.	from date of patient consent and up to 20 years after randomization of the last patient