Clinical trial NCT00014612: Comparison of Complete Axillary Lymph Node Dissection With Axillary Radiation Therapy in Treating Women With Invasive Breast Cancer
Official title: After Mapping Of The Axilla: Radiotherapy Or Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Keywords: stage IA breast cancer
stage IB breast cancer
stage II breast cancer
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
Collaborators: name: ALMANAC Trialists Group
name: Borstkanker Onderzoeksgroup Nederland
First posted: 2003-01-27
Enrollment: 4813
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells and may be a less invasive treatment and cause fewer side effects than complete axillary lymph node dissection. It is not yet known which treatment is more effective for invasive breast cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of complete axillary lymph node dissection with that of axillary radiation therapy in treating women who have invasive breast cancer.

Detailed description: OBJECTIVES:

* Compare the regional control of the axilla obtained by complete axillary lymph node dissection vs axillary radiotherapy in sentinel lymph node-positive women with operable invasive breast cancer.
* Determine whether local and regional axillary control can be obtained without axillary lymph node dissection in sentinel lymph node-negative women.
* Compare the axillary 5-year recurrence-free survival of these patients treated with these regimens.
* Compare the morbidity of patients treated with these regimens.
* Compare the quality of life of these patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center and type of breast surgery (conservation vs total mastectomy). Patients are randomized to 1 of 2 treatment arms.

Patients are given an injection of a tracer and undergo lymphoscintigraphy 2-3 hours later to identify the sentinel lymph node. Within 24 hours after lymphoscintigraphy, patients undergo wide local excision of the tumor or mastectomy after the sentinel node is removed. If no sentinel node is found or metastasis is found in a nonsentinel node, patients undergo complete axillary lymph node dissection (ALND) regardless of randomization. Sentinel node-negative patients receive no further treatment. Sentinel node-positive patients continue treatment according to randomization.

* Arm I: Within 8 weeks after surgery, patients undergo complete ALND.
* Arm II: Within 8 weeks after surgery, patients undergo axillary lymph node radiotherapy daily 5 days a week for 5 weeks.

Patients in arm I may receive postoperative axillary irradiation if 4 or more nodes are positive and more than 1 axillary level is involved.

Quality of life is assessed at baseline and then at 1, 2, 3, and 5 years.

Patients are followed annually for 5 years.

PROJECTED ACCRUAL: A total of 3,485 patients (1,394 sentinel node-positive and 2,091 sentinel node-negative) will be accrued for this study within 3 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically or "triple diagnosis" (palpation, mammogram or ultrasound, and cytology) confirmed operable invasive breast cancer

  * T0-2, N0
  * Diagnosis by excisional tumorectomy allowed
  * Clinically occult invasive disease must be histologically confirmed
* Only 1 tumor in 1 breast

  * Tumor between 5 and 50 mm in largest diameter, within 1 quadrant by mammogram, ultrasound or MRI

    * Multifocal (i.e., within one quadrant and sharing the same histological characteristics) is allowed
    * Multicentric (i.e., in different quadrants) breast cancer is not allowed
* Clinically negative axillary lymph nodes
* No metastatic disease
* No previous treatment of the primary breast tumor by neoadjuvant hormonal or systemic treatment
* Hormone receptor status:

  * Not specified

PATIENT CHARACTERISTICS:

Age:

* Any age

Sex:

* Female

Menopausal status:

* Not specified

Performance status:

* Not specified

Life expectancy:

* Not specified

Hematopoietic:

* Not specified

Hepatic:

* Not specified

Renal:

* Not specified

Other:

* Fit to undergo sentinel node biopsy, axillary clearance, breast surgery, and/or axillary radiotherapy
* No psychological, familial, sociological, or geographical condition that would preclude study compliance
* No other prior malignancy except basal cell skin cancer or carcinoma in situ of the cervix
* Not pregnant

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Not specified

Chemotherapy:

* Not specified

Endocrine therapy:

* Not specified

Radiotherapy:

* No prior radiotherapy to axilla

Surgery:

* No prior surgery to axilla

Other:

* See Disease Characteristics

Primary outcomes:
measure: Axillary recurrence rate
timeFrame: from randomization
Secondary outcomes:
measure: Shoulder function as assessed by arm function test questionnaire at baseline, 1, 3, and 5 years after surgery
timeFrame: from randomization
measure: Quality of life as measured by Quality of Life Questionnaire Core 30 Items (QLQ-C30) and QLQ-BR25 at baseline, 1, 2, 3, and 5 years after surgery
timeFrame: from randomization
measure: Axillary recurrence-free survival
timeFrame: from randomization
measure: Disease-free survival
timeFrame: from randomization
measure: Overall survival
timeFrame: from randomization
Other outcomes:
Locations:
city: Grenoble
country: France
facility: CHU de Grenoble - Hopital de la Tronche
city: Lille
country: France
facility: Centre Oscar Lambret
city: Firenze (Florence)
country: Italy
facility: Universita Degli Studi di Florence - Policlinico di Careggi
city: Turin
country: Italy
facility: Azienda Sanitaria Ospedale San Giovanni Battista Molinette di Torino
city: 's-Gravenhage
country: Netherlands
facility: HagaZiekenhuis - Locatie Leyenburg
city: Amstelveen
country: Netherlands
facility: Ziekenhuis Amstelland
city: Amsterdam
country: Netherlands
facility: Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum at University of Amsterdam
city: Apeldoorn
country: Netherlands
facility: Gelre Ziekenhuizen - Lokatie Lukas
city: Arnhem
country: Netherlands
facility: Rijnstate Hospital
city: Delft
country: Netherlands
facility: Reinier de Graaf Group - Delft
city: Den Haag
country: Netherlands
facility: HagaZiekenhuis - Locatie Rode Kruis
city: Den Haag
country: Netherlands
facility: Ziekenhuis Bronovo
city: Drachten
country: Netherlands
facility: NIJ Smellinghe
city: Eindhoven
country: Netherlands
facility: Catharina Ziekenhuis
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Haarlem
country: Netherlands
facility: Kennemer Gasthuis - Locatie EG
city: Hardenberg
country: Netherlands
facility: Ropcke-Zweers Ziekenhuis
city: Harderwijk
country: Netherlands
facility: Ziekenhuis St. Jansdal
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Nijmegen
country: Netherlands
facility: Universitair Medisch Centrum St. Radboud - Nijmegen
city: Roermond
country: Netherlands
facility: Saint Laurentius Ziekenhuis
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
city: Gdansk
country: Poland
facility: Medical University of Gdansk
city: Ljubljana
country: Slovenia
facility: Institute of Oncology - Ljubljana
city: Geneva
country: Switzerland
facility: Hopital Cantonal Universitaire de Geneve
city: Istanbul
country: Turkey
facility: Marmara University Hospital
city: Manchester
country: United Kingdom
facility: Wythenshawe Hospital
state: England
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
state: Wales
Study officials:
affiliation: The Netherlands Cancer Institute
name: Emiel JT Rutgers
role: STUDY_CHAIR
affiliation: Cardiff and Vale University Health Board - University Hospital of Wales, Cardiff
name: Robert Mansel
role: STUDY_CHAIR
affiliation: Leiden University Medical Centre, Leiden
name: Cornelis Van De Velde
role: STUDY_CHAIR
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam, Amsterdam
name: Geertjan Van Tienhoven
role: STUDY_CHAIR
References:
citation: Straver ME, Meijnen P, van Tienhoven G, van de Velde CJ, Mansel RE, Bogaerts J, Demonty G, Duez N, Cataliotti L, Klinkenbijl J, Westenberg HA, van der Mijle H, Hurkmans C, Rutgers EJ. Role of axillary clearance after a tumor-positive sentinel node in the administration of adjuvant therapy in early breast cancer. J Clin Oncol. 2010 Feb 10;28(5):731-7. doi: 10.1200/JCO.2008.21.7554. Epub 2009 Dec 28.
citation: Straver ME, Meijnen P, van Tienhoven G, van de Velde CJ, Mansel RE, Bogaerts J, Duez N, Cataliotti L, Klinkenbijl JH, Westenberg HA, van der Mijle H, Snoj M, Hurkmans C, Rutgers EJ. Sentinel node identification rate and nodal involvement in the EORTC 10981-22023 AMAROS trial. Ann Surg Oncol. 2010 Jul;17(7):1854-61. doi: 10.1245/s10434-010-0945-z. Epub 2010 Mar 19.
citation: Straver ME, Meijnen P, van Tienhoven G, et al.: Technical aspects of the sentinel node biopsy in the EORTC AMAROS sentinel node trial. [Abstract] 31st Annual San Antonio Breast Cancer Symposium, December 10-14, 2008, San Antonio, Texas. A-1006, 2008.
citation: Meijnen P, Rutgers EJT, van de Velde CJH, et al.: EORTC 10981-22023 trial. AMAROS: after mapping of the axilla: radiotherapy or surgery? Trial update. [Abstract] Eur J Cancer 2 (Suppl 3): A-79, 79, 2004.
citation: Hurkmans CW, Borger JH, Rutgers EJ, van Tienhoven G; EORTC Breast Cancer Cooperative Group; Radiotherapy Cooperative Group. Quality assurance of axillary radiotherapy in the EORTC AMAROS trial 10981/22023: the dummy run. Radiother Oncol. 2003 Sep;68(3):233-40. doi: 10.1016/s0167-8140(03)00194-4.
citation: Donker M, Slaets L, van Tienhoven G, Rutgers EJ. [Axillary lymph node dissection versus axillary radiotherapy in patients with a positive sentinel node: the AMAROS trial]. Ned Tijdschr Geneeskd. 2015;159:A9302. Dutch.
citation: Donker M, van Tienhoven G, Straver ME, Meijnen P, van de Velde CJ, Mansel RE, Cataliotti L, Westenberg AH, Klinkenbijl JH, Orzalesi L, Bouma WH, van der Mijle HC, Nieuwenhuijzen GA, Veltkamp SC, Slaets L, Duez NJ, de Graaf PW, van Dalen T, Marinelli A, Rijna H, Snoj M, Bundred NJ, Merkus JW, Belkacemi Y, Petignat P, Schinagl DA, Coens C, Messina CG, Bogaerts J, Rutgers EJ. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS): a randomised, multicentre, open-label, phase 3 non-inferiority trial. Lancet Oncol. 2014 Nov;15(12):1303-10. doi: 10.1016/S1470-2045(14)70460-7. Epub 2014 Oct 15.
citation: Donker M, Straver ME, van Tienhoven G, van de Velde CJ, Mansel RE, Litiere S, Werutsky G, Duez NJ, Orzalesi L, Bouma WH, van der Mijle H, Nieuwenhuijzen GA, Veltkamp SC, Helen Westenberg A, Rutgers EJ. Comparison of the sentinel node procedure between patients with multifocal and unifocal breast cancer in the EORTC 10981-22023 AMAROS Trial: identification rate and nodal outcome. Eur J Cancer. 2013 Jun;49(9):2093-100. doi: 10.1016/j.ejca.2013.02.017. Epub 2013 Mar 19.