Clinical trial NCT00002851: Lymph Node Radiation Therapy in Patients With Stage I, Stage II, or Stage III Breast Cancer That Has Been Surgically Removed
Official title: PHASE III RANDOMISED TRIAL INVESTIGATING THE ROLE OF INTERNAL MAMMARY AND MEDIAL SUPRACLAVICULAR (IM-MS) LYMPH NODE CHAIN IRRADIATION IN STAGE I-III BREAST CANCER
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Breast Cancer
Keywords: stage I breast cancer
stage II breast cancer
stage IIIA breast cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Enrollment: 4000
Sex: FEMALE
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Radiation therapy may kill any tumor cells remaining after surgery.

PURPOSE: This randomized phase III trial is studying radiation therapy to see how well it works compared to no further therapy in treating women with stage I, stage II, or stage III breast cancer that has been surgically removed.

Detailed description: OBJECTIVES:

* Compare the effect of irradiation of the homolateral internal mammary and medial supraclavicular lymph node chains vs no further therapy on survival, disease-free survival, metastasis-free survival, and cause of death in women with resected stage I/II/III breast cancer.

OUTLINE: This is a randomized, multicenter study. Patients are stratified by participating institution, tumor location, type of prior breast surgery, pathologic T and N stage, menopausal status, and time sequence of radiotherapy and adjuvant chemotherapy. Patients are randomized to 1 of 2 arms.

* Arm I: Patients receive no nodal irradiation.
* Arm II: Patients receive irradiation of the internal mammary and medial supraclavicular lymph node chains delivered at 1 fraction per day, 5 sessions per week, for a total of 25 fractions over 5 weeks. Radiotherapy must begin no later than 8 weeks after surgery. If adjuvant chemotherapy is given, radiotherapy begins within 6 weeks after the last course of chemotherapy and within 8 months after surgery.

Patients are followed at least yearly after randomization for up to 20 years.

PROJECTED ACCRUAL: A total of 4,000 patients will be accrued for this study within 4 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed unilateral adenocarcinoma of the breast
* Stage I/II/III (Tx, T0-3, N0-2) disease in one of the following categories or multifocal tumors if one of the foci is in agreement with the following:

  * Centrally or medially located with any lymph node status

    * Central location defined as underlying the areola
    * Medial location defined as at least partial involvement of upper or lower medial quadrant of breast
  * Externally located with axillary node involvement
* Prior mastectomy or breast-conserving surgery and axillary dissection required

  * Sentinel node procedure as axillary intervention without further axillary surgery is allowed
  * No prior internal mammary chain dissection
  * No upper inner lesion treated with breast-conserving surgery that precludes sparing of internal mammary lymph node chain from radiotherapy volume

    * Decision at radiation oncologist's discretion
* Hormone receptor status:

  * Not specified

PATIENT CHARACTERISTICS:

Age:

* 75 and under

Sex:

* Female

Menopausal status:

* Not specified

Performance status:

* Not specified

Hematopoietic:

* Not specified

Hepatic:

* Not specified

Renal:

* Not specified

Cardiovascular:

* No prior cardiac disease

Other:

* No prior malignancy except adequately treated nonmelanomatous skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Not specified

Chemotherapy:

* Not specified

Endocrine therapy:

* Not specified

Radiotherapy:

* Not specified

Surgery:

* See Disease Characteristics

Other:

* Concurrent enrollment in other randomized trials allowed

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Antwerp
country: Belgium
facility: Ziekenhuis Network Antwerpen Middelheim
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Haine Saint Paul
country: Belgium
facility: Hopital de Jolimont
city: Kortrijk
country: Belgium
facility: Cazk Groeninghe - Campus Maria's Voorzienigheid
city: Leuven
country: Belgium
facility: U.Z. Gasthuisberg
city: Wilrijk
country: Belgium
facility: Algemeen Ziekenhuis Sint-Augustinus
city: Sarajevo
country: Bosnia and Herzegovina
facility: Institute of Oncology - Clinical Center University of Sarajevo
city: Santiago
country: Chile
facility: Instituto de Radiomedicina
city: Santiago
country: Chile
facility: Clinica Alemana
city: Besancon
country: France
facility: CHR de Besancon - Hopital Jean Minjoz
city: Bordeaux
country: France
facility: Institut Bergonie
city: Dijon
country: France
facility: Centre de Lutte Contre le Cancer Georges-Francois Leclerc
city: Grenoble
country: France
facility: CHU de Grenoble - Hopital de la Tronche
city: Marseille
country: France
facility: Service Cancerologie Polyclinique Clairval
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Rennes
country: France
facility: Centre Eugene Marquis
city: Strasbourg
country: France
facility: Centre Hospitalier Universitaire Henri Mondor
city: Strasbourg
country: France
facility: Centre Leon Berard
city: Strasbourg
country: France
facility: Centre Paul Strauss
city: Strasbourg
country: France
facility: Institut Gustave Roussy
city: Berlin
country: Germany
facility: Charite - Campus Charite Mitte
city: Berlin
country: Germany
facility: Robert Roessle Comprehensive Cancer Center at University of Berlin - Charite Campus Buch
city: Cologne
country: Germany
facility: Klinik I fuer Innere Medizin
city: Erlangen
country: Germany
facility: University of Erlangen-Nuremberg
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
city: Goettingen
country: Germany
facility: Universitaetsklinikum Goettingen
city: Tuebingen
country: Germany
facility: Universitaetsklinikum Tuebingen
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Ramat-Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Como
country: Italy
facility: Ospedale Sant Anna
city: Genoa (Genova)
country: Italy
facility: Istituto Nazionale per la Ricerca sul Cancro
city: 's-Gravenhage (Den Haag, the Hague)
country: Netherlands
facility: Medisch Centrum Haaglanden
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum
city: Blaricum
country: Netherlands
facility: Streekziekenhuis Gooi-Noord
city: Deventer
country: Netherlands
facility: Radiotherapeutisch Instituut-(Riso)
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente
city: Groningen
country: Netherlands
facility: Academisch Ziekenhuis Groningen
city: Maastricht
country: Netherlands
facility: Radiotherapeutisch Instituut Limburg-Maastricht
city: Tilburg
country: Netherlands
facility: Dr. Bernard Verbeeten Instituut
city: Utrecht
country: Netherlands
facility: Academisch Ziekenhuis Utrecht
city: Gdansk
country: Poland
facility: Medical University of Gdansk
city: Porto
country: Portugal
facility: Instituto Portugues de Oncologia Centro do Porto, SA
city: Barcelona
country: Spain
facility: Institut Catala D'Oncologia
city: Geneva
country: Switzerland
facility: Hopital Cantonal Universitaire de Geneve
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: Zurich
country: Switzerland
facility: UniversitaetsSpital
city: Istanbul
country: Turkey
facility: Istanbul University-Institute of Oncology
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital NHS Trust
state: England
Study officials:
affiliation: University Hospital, Gasthuisberg
name: Walter F. Van den Bogaert, MD, PhD
affiliation: Medisch Centrum Haaglanden Westeinde
name: H. Struikmans, MD, PhD
affiliation: Institut Curie
name: Alain Fourquet, MD
affiliation: The Netherlands Cancer Institute
name: Harry Bartelink, MD, PhD
References:
citation: Matzinger O, Heimsoth I, Poortmans P, Collette L, Struikmans H, Van Den Bogaert W, Fourquet A, Bartelink H, Ataman F, Gulyban A, Pierart M, Van Tienhoven G; EORTC Radiation Oncology & Breast Cancer Groups. Toxicity at three years with and without irradiation of the internal mammary and medial supraclavicular lymph node chain in stage I to III breast cancer (EORTC trial 22922/10925). Acta Oncol. 2010;49(1):24-34. doi: 10.3109/02841860903352959.
citation: Musat E, Poortmans P, Van den Bogaert W, Struikmans H, Fourquet A, Bartelink H, Kirkove C, Budach V, Pierart M, Collette L. Quality assurance in breast cancer: EORTC experiences in the phase III trial on irradiation of the internal mammary nodes. Eur J Cancer. 2007 Mar;43(4):718-24. doi: 10.1016/j.ejca.2006.11.015. Epub 2007 Jan 19.
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citation: Poortmans PM, Venselaar JL, Struikmans H, Hurkmans CW, Davis JB, Huyskens D, van Tienhoven G, Vlaun V, Lagendijk JJ, Mijnheer BJ, De Winter KA, Van der Hulst MH, Van den Bogaert WF. The potential impact of treatment variations on the results of radiotherapy of the internal mammary lymph node chain: a quality-assurance report on the dummy run of EORTC Phase III randomized trial 22922/10925 in Stage I--III breast cancer(1). Int J Radiat Oncol Biol Phys. 2001 Apr 1;49(5):1399-408. doi: 10.1016/s0360-3016(00)01549-2.
citation: Poortmans P, Van Den Bogaert W, Venselaar J, et al.: Quality assurance in EORTC trial 22922/10925 concerning internal mammary chain (IMC) irradiation: the dummy run. Radiother Oncol 48(suppl 1): A735, s186, 1998.
citation: Poortmans P, Van Den Bogaert W, Venselaar J, et al.: EORTC randomized phase III trials 22922/10925 investigating the role of internal mammary chain (IMC) irradiation in stage I-II breast cancer: a quality assurance report on the dummy run. Eur J Cancer 34(suppl 5): A257, s58, 1998.
citation: Kaidar-Person O, Fortpied C, Hol S, Weltens C, Kirkove C, Budach V, Peignaux-Casasnovas K, van der Leij F, Vonk E, Valli M, Weidner N, Guckenberger M, Koiter E, Fourquet A, Bartelink H, Struikmans H, Poortmans P; EORTC Radiation Oncology and Breast Cancer Groups. The association of internal mammary and medial supraclavicular lymph node radiation technique with clinical outcomes: Results from the EORTC 22922/10925 randomised trial. Radiother Oncol. 2022 Jul;172:99-110. doi: 10.1016/j.radonc.2022.05.006. Epub 2022 May 12.
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