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

• ClinicalTrials.gov Identifier: NCT03513614
• Recruitment Status: Recruiting
• First Posted: May 1, 2018
• Last Update Posted: February 15, 2021
• Sponsor: Swiss Group for Clinical Cancer Research
• Collaborators: International Breast Cancer Study Group; Austrian Breast Cancer Study Group
• Information provided by (Responsible Party): Swiss Group for Clinical Cancer Research

Tracking Information

• First Submitted Date: April 19, 2018
• First Posted Date: May 1, 2018
• Last Update Posted Date: February 15, 2021
• Actual Study Start Date: August 7, 2018
• Estimated Primary Completion Date: March 31, 2029 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 30, 2018)

Disease-free survival (DFS) [ Time Frame: 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 30, 2018)

• Overall survival (OS) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Node-positive Breast Cancer

Intervention

• Procedure: Tailored axillary surgery
  Sentinel lymph node procedure combined with the documentation of the successful removal of the clipped node by specimen radiography and the removal of all palpably suspicious nodes.
• Radiation: Radiotherapy - Arm A
  Breast/chest wall and regional nodal irradiation excluding the dissected axilla as a target volume.
• Radiation: Radiotherapy - Arm B
  Breast/chest wall and regional nodal irradiation including the full axilla.

Study Arms

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

  • Procedure: Tailored axillary surgery
  • Radiation: Radiotherapy - Arm A
• Active Comparator: No ALND
  Tailored axillary surgery followed by regional nodal irradiation including the full axilla.
  Interventions:

  • Procedure: Tailored axillary surgery
  • Radiation: Radiotherapy - Arm B

• Publications *: Henke G, Knauer M, Ribi K, Hayoz S, Gérard MA, Ruhstaller T, Zwahlen DR, Muenst S, Ackerknecht M, Hawle H, Fitzal F, Gnant M, Mátrai 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.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 30, 2018): 1500
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2043
• Estimated Primary Completion Date: March 31, 2029 (Final data collection date for primary outcome measure)

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
• 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

• 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Marie-Aline Gerard, PhD; +41 31 389 91 91; trials@sakk.ch

• Listed Location Countries: Austria, Germany, Hungary, Italy, Lithuania, Switzerland

Administrative Information

• NCT Number: NCT03513614
• Other Study ID Numbers: SAKK 23/16 - TAXIS; 2018-000372-14 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Swiss Group for Clinical Cancer Research
• Study Sponsor: Swiss Group for Clinical Cancer Research

Collaborators

• International Breast Cancer Study Group
• Austrian Breast Cancer Study Group

Investigators

• Study Chair: Walter P. Weber, Prof; University Hospital, Basel, Switzerland

• PRS Account: Swiss Group for Clinical Cancer Research
• Verification Date: February 2021