Node-positive Breast Cancer
Conditions
Keywords
Tailored Axillary Surgery, TAXIS, Breast Cancer, node-positive breast cancer, phase III trial, IBCSG 57-18, ABCSG
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.
Interventions
PROCEDURETailored axillary surgery - both Arms
Axillary lymph node dissection - Arm A
RADIATIONRadiotherapy - Arm A
Regional nodal irradiation excluding the dissected axilla - Arm A
RADIATIONRadiotherapy - Arm B
Regional nodal irradiation including the full axilla - Arm B
Sponsors
University Hospital, Basel, Switzerland
ETOP IBCSG Partners Foundation
Austrian Breast Cancer Study Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Argentina, Austria, Canada, Croatia, Germany, Greece, Hungary, Italy, Latvia, Lithuania, South Korea, Switzerland, United States
Contacts
STUDY_CHAIRWalter P. Weber, Prof.
University Hospital, Basel, Switzerland
Outcome results
None listed