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

Sponsor

University Hospital, Basel, Switzerland (Other)

Overall Status

Recruiting

CT.gov ID

NCT03513614

Collaborator

ETOP IBCSG Partners Foundation (Other), Austrian Breast Cancer Study Group (Other)

1,500

Enrollment

Locations

Arms

195.8

Anticipated Duration (Months)

33.3

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Node-positive Breast Cancer	Procedure: Tailored axillary surgery - both Arms Radiation: Radiotherapy - Arm A Radiation: Radiotherapy - Arm B	N/A

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

1500 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Aug 7, 2018

Anticipated Primary Completion Date :

Dec 1, 2029

Anticipated Study Completion Date :

Dec 1, 2034

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: ALND Tailored axillary surgery followed by axillary lymph node dissection (ALND) and regional nodal irradiation excluding the dissected axilla.	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
Active Comparator: No ALND Tailored axillary surgery followed by regional nodal irradiation including the full axilla.	Procedure: Tailored axillary surgery - both Arms Axillary lymph node dissection - Arm A Radiation: Radiotherapy - Arm B Regional nodal irradiation including the full axilla - Arm B

Arm

Intervention/Treatment

Active Comparator: ALND

Tailored axillary surgery followed by axillary lymph node dissection (ALND) and regional nodal irradiation excluding the dissected axilla.

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

Active Comparator: No ALND

Tailored axillary surgery followed by regional nodal irradiation including the full axilla.

Procedure: Tailored axillary surgery - both Arms

Axillary lymph node dissection - Arm A

Radiation: Radiotherapy - Arm B

Regional nodal irradiation including the full axilla - Arm B

Outcome Measures

Primary Outcome Measures

Disease-free survival (DFS) [at the occurrence of the event or latest 20 years after randomization of the last patient]
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.

Secondary Outcome Measures

Overall survival (OS) [at the occurrence of the event or latest 20 years after randomization of the last patient]
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.
Breast cancer-specific survival (BCSS) [at the occurrence of the event or latest 20 years after randomization of the last patient]
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.
Time to local recurrence (TTLR) [at the occurrence of the event or latest 20 years after randomization of the last patient]
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.
Time to distant recurrence (TTDR) [at the occurrence of the event or latest 20 years after randomization of the last patient]
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.
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.]
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.]
Adverse events according to NCI CTCAE v4.03 [from date of patient consent and up to 20 years after randomization of the last patient]
Clipping-related AEs and specific AEs related to the surgical procedure and radiotherapy will be assessed according to NCI CTCAE v4.03.
Late radiotherapy-related adverse events [from date of patient consent and up to 20 years after randomization of the last patient]
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
Surgical site infections (SSI) [from date of patient consent and up to 20 years after randomization of the last patient]
SSIs will be assessed according to the Centers for Disease Control and Prevention Surgical Site Infection Classification System.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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
Planned neoadjuvant treatment (e.g. chemotherapy or endocrine therapy) allowed
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 without neoadjuvant treatment
Node-positivity detected by palpation (cN1-2) and confirmed by pathology without neoadjuvant treatment. Note: occult breast cancer is allowed, if biopsy-proven axillary lymphatic metastasis is present
Eligible for primary ALND or sentinel lymph node procedure with frozen section and either:
Newly diagnosed
Isolated in-breast recurrence or second ipsilateral breast cancer (at least 5 years disease free and no prior axillary surgery or loco regional RT)
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 [42] stage II-III (all molecular subtypes allowed):
Node-positivity initially detected by imaging (negative on palpation) and reconfirmed by pathology (residual disease) (in SLN or non SLN during surgery) after neoadjuvant treatment
Node-positivity initially detected by palpation and reconfirmed by pathology (residual disease) after neoadjuvant treatment

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.

Clinical N3 breast cancer
Clinical N2 breast cancer, if limited to the internal mammary nodes only
Contralateral breast cancer
Prior axillary surgery (except prior sentinel node procedure in breast recurrence)
Prior regional radiotherapy
History of hematologic or primary solid tumor malignancy, unless in remission for at least 5 years from pre-registration with the exception of adequately treated cervical carcinoma in situ or localized non-melanoma skin cancer.
Concurrent treatment with any other experimental drug within 30 days of pre-registration
Concomitant use of other anti-cancer drugs or radiotherapy
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
No palpable disease left behind in the axilla during Tailored Axillary Surgery
Sentinel lymph node outside the axilla

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Krankenhaus Dornbirn	Dornbirn	Austria	6850
2	Landeskrankenhaus Feldkirch	Feldkirch	Austria	6800
3	Tirol Kliniken - Landeskrankenhaus Innsbruck	Innsbruck	Austria	6020
4	Ordens Kinikum Linz, Barmherzige Schwestern	Linz	Austria	4010
5	Klinikum Wels-Grieskrichen GmbH	Wels	Austria	4600
6	Medizinische Universität Wien - Klinik für Chirurgie	Wien	Austria	1090
7	Medizinische Universität Wien - Universitätsklinik für Frauenheilkunde	Wien	Austria	1090
8	Ev. Waldkrankenhaus Spandau	Berlin	Germany	13589
9	KEM \| Evang. Kliniken Essen-Mitte gGmbH	Essen	Germany	45136
10	Niels-Stensen-Kliniken Franziskus-Hospital Harderberg	Georgsmarienhütte	Germany	49124
11	Universitätsklinikum Heidelberg	Heidelberg	Germany	69120
12	ViDia Christliche Kliniken Karlsruhe, Diakonissenkrankenhaus	Karlsruhe	Germany	76199
13	Onkologie Rheinsieg	Troisdorf	Germany	53840
14	Helios University Hospital Wuppertal	Wuppertal	Germany	42283
15	National Institute of Oncology	Budapest	Hungary	1122
16	Bacs-Kiskun Country Hospital	Kecskemet	Hungary	6000
17	University of Szeged	Szeged	Hungary	6720
18	Ospedale MultiMedica Castellanza	Castellanza	Italy	21053
19	National Cancer Institut	Vilnius	Lithuania	08660
20	Kantonsspital Aarau	Aarau	Switzerland	5001
21	Brustzentrum Basel und Netzwerk	Allschwil	Switzerland	4123
22	Kantonsspital Baden	Baden	Switzerland	5404
23	Universitätsspital Basel	Basel	Switzerland	4051
24	St. Claraspital AG	Basel	Switzerland	CH-4016
25	Brustzentrum, Klinik Engeried	Bern	Switzerland	3012
26	Kantonsspital Graubünden	Chur	Switzerland	7000
27	Clinique de Grangettes	Chêne-Bougeries	Switzerland	1224
28	Brustzentrum Thurgau	Frauenfeld	Switzerland	8501
29	Hôpital Cantonal Fribourgeois	Fribourg	Switzerland	1708
30	Clinique de Genolier	Genolier	Switzerland	1272
31	HUG - Hôpitaux Universitaires de Genève	Genève	Switzerland	1205
32	Hôpital neuchâtelois	La Chaux-de-Fonds	Switzerland	2300
33	Centre Hospitalier Universitaire Vaudois CHUV	Lausanne	Switzerland	1011
34	Hirslanden Klinik St. Anna	Lucerne	Switzerland	6006
35	Luzerner Kantonsspital - Brustzentrum	Luzern	Switzerland	6000
36	Bethesda Spital Basel, Gynäkologie und Geburtshilfe	Pratteln	Switzerland	4133
37	Spital Limmattal	Schlieren	Switzerland	8952
38	Hôpital du Valais / Hôpital de Sion	Sion	Switzerland	1951
39	Kantonsspital St. Gallen	St. Gallen	Switzerland	9007
40	Brustzentrum Ostschweiz	St. Gallen	Switzerland	9016
41	Kantonsspital Winterthur, Brustzentrum	Winterthur	Switzerland	8401
42	Spital Zollikerberg	Zollikerberg	Switzerland	8125
43	Brust-Zentrum Seefeld	Zürich	Switzerland	8008
44	Stadtspital Triemli	Zürich	Switzerland	8063
45	Universitäts Spital Zürich	Zürich	Switzerland	8091