POSNOC - A Trial Looking at Axillary Treatment in Early Breast Cancer

Study Overview
=================
Brief Summary
-----------------
POSNOC is a pragmatic, randomised, multicentre, non-inferiority trial. Aim For women with early stage breast cancer and one or two sentinel node macrometastases, to assess whether adjuvant therapy alone is no worse than adjuvant therapy plus axillary treatment, in terms of axillary recurrence within 5 years. Stratification: Institution, Age (<50, ≥50), Breast-conserving surgery (BCS) or mastectomy, Estrogen receptor (ER) status (positive, negative), Number of positive nodes (1, 2), Intra-operative sentinel assessment using OSNA (yes, no). Interventions The study will compare adjuvant therapy alone with adjuvant therapy plus axillary treatment (axillary node clearance (ANC) or axillary radiotherapy (ART)). Sample Size: 1900 participants Follow-up: Participants will be followed up for 5 years. Adjuvant Therapy: All participants will receive adjuvant systemic therapy (chemotherapy and/or endocrine therapy). All participants may receive breast/chest wall radiotherapy. Axillary and supraclavicular fossa radiotherapy is not allowed when randomised to adjuvant therapy alone.

Official Title
-----------------
POSNOC - POsitive Sentinel NOde: Adjuvant Therapy Alone Versus Adjuvant Therapy Plus Clearance or Axillary Radiotherapy. A Randomised Controlled Trial of Axillary Treatment in Women With Early Stage Breast Cancer Who Have Metastases in One or Two Sentinel Nodes

Conditions
-----------------
Breast Cancer

Intervention / Treatment
-----------------
* Other: Adjuvant therapy
* Procedure: Axillary treatment


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Unifocal or multi-focal invasive tumour with lesion ≤5 cm in its largest dimension, measured pathologically or largest invasive tumour diameter on radiology should be used for women who are randomised intra-operatively or undergo sentinel node biopsy before neoadjuvant therapy (tumour size should be based only on the single largest tumour; do not add the sizes together from the multiple foci) At sentinel node biopsy have 1 or 2 nodes with macrometastases (tumour deposit >2.0mm in largest dimension or defined as macrometastasis on molecular assay) Fit for axillary treatment and adjuvant therapy Have given written informed consent Exclusion Criteria: bilateral invasive breast cancer more than 2 nodes with macrometastases neoadjuvant therapy for breast cancer except: if sentinel node biopsy performed prior to neoadjuvant chemotherapy in women with early breast cancer short duration of neoadjuvant endocrine therapy is acceptable (up to 3 months) previous axillary surgery on the same body side as the scheduled sentinel node biopsy not receiving adjuvant systemic therapy previous cancer less than 5 years previously or concomitant malignancy except: basal or squamous cell carcinoma of the skin in situ carcinoma of the cervix in situ melanoma contra- or ipsilateral in situ breast cancer

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adjuvant therapy alone<br>Women in this arm will have adjuvant therapy but no treatment to their armpit after surgery. Axillary and supraclavicular fossa radiotherapy is not allowed when randomised to this arm. | Other: Adjuvant therapy<br>* Adjuvant therapy will include chemotherapy and/or endocrine therapy for all women, and radiotherapy to breast or chest wall if indicated. Human epidermal growth factor receptor 2 (HER2) targeted treatment may also be administered when indicated.<br>|
| Active Comparator: Adjuvant therapy plus axillary treatment<br>Women in this arm will have adjuvant therapy plus treatment to their armpit after surgery. Axillary treatment can be axillary node clearance or axillary radiotherapy as per local guidelines. | Other: Adjuvant therapy<br>* Adjuvant therapy will include chemotherapy and/or endocrine therapy for all women, and radiotherapy to breast or chest wall if indicated. Human epidermal growth factor receptor 2 (HER2) targeted treatment may also be administered when indicated.<br>Procedure: Axillary treatment<br>* Axillary treatment can be axillary node clearance or axillary radiotherapy as per local guidelines.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Axillary recurrence | Axillary recurrence is defined as pathologically (cytology or biopsy) confirmed recurrence in lymph nodes draining the primary tumour site. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Arm morbidity | Arm morbidity will be assessed by the Lymphoedema and Breast Cancer and QuickDASH (disabilities of the arm, shoulder and hand) questionnaires. | 3 years | 
| Quality of life | Quality of life will be assessed using the Functional Assessment of Cancer Therapy-Breast+4 questionnaire. | 3 years | 
| Anxiety (Spielberger State/Trait Anxiety Inventory) | Anxiety will be assessed with the Spielberger State/Trait Anxiety Inventory. | 3 years | 
| Economic evaluation (EQ-5D-5L (EuroQoL) | Health-related quality of life will be evaluated using the EQ-5D-5L (EuroQoL) instrument. | 3 years | 
| Local (breast or chest wall) recurrence | Number of participants with local (breast or chest wall) recurrence. | 5 years | 
| Regional (nodal) recurrence | Number of participants with regional (nodal) recurrence. | 5 years | 
| Distant metastasis | Number of participants with distant metastasis. | 5 years | 
| Time to axillary recurrence |  | 5 years | 
| Axillary recurrence free survival |  | 5 years | 
| Disease free survival |  | 5 years | 
| Overall survival |  | 5 years | 
| Contralateral breast cancer | Number of participants with contralateral breast cancer. | 5 years | 
| Non-breast malignancy | Number of participants with non-breast malignancy. | 5 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
breast cancer, sentinel lymph node biopsy, axillary lymph node clearance, axillary lymph node dissection, macrometastases, axillary radiotherapy, POSNOC