Clinical trial NCT03513614: Tailored Axillary Surgery With or Without Axillary Lymph Node Dissection Followed by Radiotherapy in Patients With Clinically Node-positive Breast Cancer (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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Node-positive Breast Cancer
Keywords: Tailored Axillary Surgery
TAXIS
Breast Cancer
node-positive breast cancer
phase III trial
IBCSG 57-18
ABCSG
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
Collaborators: name: ETOP IBCSG Partners Foundation
name: Austrian Breast Cancer Study Group
First posted: 2018-05-01
Enrollment: 1500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Disease-free survival (DFS)
timeFrame: at the occurrence of the event or latest 20 years after randomization of the last patient
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: at the occurrence of the event or latest 20 years after randomization of the last patient
measure: Breast cancer-specific survival (BCSS)
timeFrame: at the occurrence of the event or latest 20 years after randomization of the last patient
measure: Time to local recurrence (TTLR)
timeFrame: at the occurrence of the event or latest 20 years after randomization of the last patient
measure: Time to distant recurrence (TTDR)
timeFrame: at the occurrence of the event or latest 20 years after randomization of the last patient
measure: Physician reported morbidity outcomes (Lymphedema)
timeFrame: 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.
measure: Physician reported morbidity outcomes (Decreased range of shoulder motion)
timeFrame: 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.
measure: Adverse events according to NCI CTCAE v4.03
timeFrame: from date of patient consent and up to 20 years after randomization of the last patient
measure: Late radiotherapy-related adverse events
timeFrame: from date of patient consent and up to 20 years after randomization of the last patient
measure: Surgical site infections (SSI)
timeFrame: from date of patient consent and up to 20 years after randomization of the last patient
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: Walter Reed National Military Medical Center
state: Maryland
city: Durham
country: United States
facility: Duke University/Duke Cancer Center
state: North Carolina
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Rosario
country: Argentina
facility: Sanatorio Parque Breast Cancer Center
state: Santa Fe
city: Buenos Aires
country: Argentina
facility: Institute of Oncology "Angel H. Roffo
city: Dornbirn
country: Austria
facility: Krankenhaus Dornbirn
city: Feldkirch
country: Austria
facility: Landeskrankenhaus Feldkirch
city: Innsbruck
country: Austria
facility: Medical University of Innsbruck, Department of Gynecology
city: Linz
country: Austria
facility: Ordens Kinikum Linz, Barmherzige Schwestern
city: Salzburg
country: Austria
facility: Universitätsklinik für Frauenheilkunde und Geburtshilfe; Landeskrankenhaus Salzburg der PMU
city: Vienna
country: Austria
facility: Hanusch Hospital Vienna
city: Wels
country: Austria
facility: Klinikum Wels-Grieskrichen GmbH
city: Wien
country: Austria
facility: Medizinische Universität Wien - Klinik für Chirurgie
city: Wien
country: Austria
facility: Medizinische Universität Wien - Universitätsklinik für Frauenheilkunde
city: Montréal
country: Canada
facility: CIUSSS du Centre Ouest-de-l'Île-de-Montréal, Jewish General Hospital
city: Rijeka
country: Croatia
facility: Breast Centre of Clinical Hospital
city: Zagreb
country: Croatia
facility: HRUHC Sestre milosdrnice
city: Berlin
country: Germany
facility: Ev. Waldkrankenhaus Spandau
city: Essen
country: Germany
facility: KEM | Evang. Kliniken Essen-Mitte gGmbH
city: Georgsmarienhütte
country: Germany
facility: Niels-Stensen-Kliniken Franziskus-Hospital Harderberg
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg, Sektion Senologie
city: Karlsruhe
country: Germany
facility: ViDia Christliche Kliniken Karlsruhe, Diakonissenkrankenhaus
city: Troisdorf
country: Germany
facility: Onkologie Rheinsieg
city: Wuppertal
country: Germany
facility: Helios University Hospital Wuppertal
city: Chaidari
country: Greece
facility: Attikon University Hospital
state: Athens
city: Heraklion
country: Greece
facility: University Hospital of Heraklion
state: Crete
city: Athens
country: Greece
facility: Alexandra General Hospital
city: Larisa
country: Greece
facility: Larissa General University Hospital
city: Marousi
country: Greece
facility: Iaso Maternity Hospital
city: Maroúsi
country: Greece
facility: Athens Medical Center Iatriko
city: Patras
country: Greece
facility: University Hospital of Patras
city: Budapest
country: Hungary
facility: National Institute of Oncology
city: Kecskemet
country: Hungary
facility: Bacs-Kiskun Country Hospital
city: Szeged
country: Hungary
facility: University of Szeged
city: Castellanza
country: Italy
facility: Ospedale MultiMedica Castellanza
city: Rome
country: Italy
facility: Fondazione Policlinico Universitario "Agostino Gemelli" di Roma
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Rīga
country: Latvia
facility: Pauls Stradinš Clinical University Hospital
city: Vilnius
country: Lithuania
facility: National Cancer Institut
city: Aarau
country: Switzerland
facility: Kantonsspital Aarau
city: Allschwil
country: Switzerland
facility: Brustzentrum Basel und Netzwerk
city: Baden
country: Switzerland
facility: Kantonsspital Baden
city: Basel
country: Switzerland
facility: Universitätsspital Basel
city: Basel
country: Switzerland
facility: Bethesda Spital Basel, Gynäkologie und Geburtshilfe
city: Basel
country: Switzerland
facility: St. Claraspital AG
city: Bern
country: Switzerland
facility: Brustzentrum Bern, Lindenhofgruppe Centerclinic
city: Chur
country: Switzerland
facility: Kantonsspital Graubünden
city: Chêne-Bougeries
country: Switzerland
facility: Clinique de Grangettes
city: Frauenfeld
country: Switzerland
facility: Brustzentrum Thurgau
city: Fribourg
country: Switzerland
facility: Breast center Fribourg
city: Genolier
country: Switzerland
facility: Clinique de Genolier
city: Genève
country: Switzerland
facility: HUG - Hôpitaux Universitaires de Genève
city: La Chaux-de-Fonds
country: Switzerland
facility: Hôpital Neuchâtelois
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois CHUV
city: Lucerne
country: Switzerland
facility: Hirslanden Klinik St. Anna
city: Lugano
country: Switzerland
facility: Centro di Senologia della Svizzera Italiana CSSI
city: Luzern
country: Switzerland
facility: Luzerner Kantonsspital - Brustzentrum
city: Schlieren
country: Switzerland
facility: Spital Limmattal
city: Sion
country: Switzerland
facility: Hôpital du Valais / Hôpital de Sion
city: St. Gallen
country: Switzerland
facility: Kantonsspital St. Gallen
city: St. Gallen
country: Switzerland
facility: Tumor-and Breast centre Ostschweiz
city: Winterthur
country: Switzerland
facility: Kantonsspital Winterthur, Brustzentrum
city: Zollikerberg
country: Switzerland
facility: Spital Zollikerberg
city: Zürich
country: Switzerland
facility: Brust-Zentrum Zürich (Seefeld)
city: Zürich
country: Switzerland
facility: Stadtspital Triemli
city: Zürich
country: Switzerland
facility: Universitäts Spital Zürich
Study officials:
affiliation: University Hospital, Basel, Switzerland
name: Walter P. Weber, Prof.
role: STUDY_CHAIR
References:
citation: 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, Simonson C, Fehr PM, Gabriel N, Maraz R, Sarlos D, Dedes KJ, Leo C, Berclaz G, Dubsky P, Exner R, Fansa H, Hager C, Reisenberger K, Singer CF, Reitsamer R, Reinisch M, Winkler J, Lam GT, Fehr MK, Naydina T, Kohlik M, Clerc K, Ostapenko V, Fitzal F, Nussbaumer R, Maggi N, Schulz A, Markellou P, Lelievre L, Egle D, Heil J, Knauer M. Tailored axillary surgery in patients with clinically node-positive breast cancer: Pre-planned feasibility substudy of TAXIS (OPBC-03, SAKK 23/16, IBCSG 57-18, ABCSG-53, GBG 101). Breast. 2021 Dec;60:98-110. doi: 10.1016/j.breast.2021.09.004. Epub 2021 Sep 8.
citation: Henke G, Knauer M, Ribi K, Hayoz S, Gerard MA, Ruhstaller T, Zwahlen DR, Muenst S, Ackerknecht M, Hawle H, Fitzal F, Gnant M, Matrai Z, Ballardini B, Gyr A, Kurzeder C, Weber WP. Tailored axillary surgery with or without axillary lymph node dissection followed by radiotherapy in patients with clinically node-positive breast cancer (TAXIS): study protocol for a multicenter, randomized phase-III trial. Trials. 2018 Dec 4;19(1):667. doi: 10.1186/s13063-018-3021-9.