Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Combination Chemotherapy After Surgery in Treating Patients With Stage I, Stage II, or Stage III Breast Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Active	Not specified	Other	IBCSG-22-00 EU-20119, NCT00022516, EUDRACT-2005-005666-36

Objectives

1. Determine the efficacy of adjuvant induction chemotherapy with or without cyclophosphamide and methotrexate as maintenance chemotherapy in patients with stage I, II, or III breast cancer.
2. Compare the disease-free survival, overall survival, and systemic disease-free survival of patients treated with these regimens.
3. Compare the toxic effects of these regimens in these patients.
4. Compare the quality of life of patients treated with these regimens.

Entry Criteria

Disease Characteristics:

• Histologically confirmed stage I, II, or III breast cancer
  • T1-3, N0-2, M0
    • Patients with sentinel node biopsy positive disease must have undergone axillary dissection
    • Tumor must be confined to the breast without detected metastases elsewhere
  • T4 disease with minimal dermal invasion allowed
  • No T4 disease with ulceration of skin, infiltration of skin (except pathologically minimal dermal involvement), peau d'orange, or inflammatory breast cancer
• No bilateral breast cancer (except in situ carcinoma) or suspicious mass in opposite breast that has not been proven benign
• No distant metastases
  • No skeletal pain of unknown cause, elevated alkaline phosphatase, or bone scan showing hot spots that cannot be ruled out as metastases by x-ray, MRI, and/or CT
• Must have undergone prior total mastectomy OR breast-conserving procedure (e.g., lumpectomy, quadrantectomy, or partial mastectomy with negative margins)
  • Patients must begin or have begun induction chemotherapy within 8 weeks after definitive surgery
• Negative surgical margins
• Axillary clearance with at least 6 lymph nodes examined

  OR

• Negative sentinel node biopsy

  OR

• Positive lymph nodes and unsuitable for taxane-based chemotherapy
• Known HER2 status by immunohistochemistry or fluorescence in situ hybridization
• Hormone receptor status:
  • Estrogen and progesterone receptor negative
    • Less than 10% positive tumor cells by immunohistochemistry

Prior/Concurrent Therapy:

Biologic therapy:

• Prior trastuzumab (Herceptin) allowed

Chemotherapy:

• See Disease Characteristics
• No prior adjuvant or neoadjuvant chemotherapy for breast cancer

Endocrine therapy:

• No prior endocrine therapy for breast cancer or prevention
• No prior tamoxifen or raloxifene for breast cancer

Radiotherapy:

• No prior radiotherapy for breast cancer except primary irradiation

Surgery:

• See Disease Characteristics

Other:

• No prior preventative therapy for breast cancer

Patient Characteristics:

Age:

• Not specified

Sex:

• Not specified

Menopausal status:

• Premenopausal, defined as less than 6 months since last menstrual period (LMP) AND no prior bilateral ovariectomy AND not on estrogen replacement (OR under age 50)

  OR

• Postmenopausal, defined as prior bilateral ovariectomy OR more than 12 months since LMP without prior hysterectomy (OR age 50 and over)

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• WBC greater than 3,000/mm3
• Platelet count greater than 100,000/mm3

Hepatic:

• See Disease Characteristics
• Bilirubin less than 2.0 mg/dL
• ALT less than 1.5 times upper limit of normal

  OR

• AST less than 60 IU/L

Renal:

• Creatinine less than 1.2 mg/dL

Other:

• Not pregnant or lactating within the past 6 months
• Fertile patients must use effective barrier contraception
• No other prior or concurrent malignancy except adequately treated basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or contralateral or ipsilateral in situ breast carcinoma
• No psychiatric or addictive disorders that would preclude study
• No non-malignant systemic disease that would preclude study

Expected Enrollment

Approximately 900 patients will be accrued for this study within 5 years.

Outcomes

Disease-free survival
Overall survival and systemic disease-free survival
Toxicity
Quality of life

Outline

This is a randomized, open-label, multicenter study. Patients are stratified according to participating center, menopausal status (pre vs post), and approved induction chemotherapy (doxorubicin and cyclophosphamide vs other agents). Patients are randomized to one of two treatment arms.

• Arm I: Patients receive one of the following approved adjuvant induction chemotherapy regimens:
  • AC comprising doxorubicin and cyclophosphamide IV on day 1 every 21 days for 4 courses followed by paclitaxel IV or docetaxel IV on day 1 every 21 days for 4 courses
  • EC comprising epirubicin and cyclophosphamide IV on day 1 every 21 days for 4 courses followed by paclitaxel IV or docetaxel IV on day 1 every 21 days for 4 courses
  • FAC comprising cyclophosphamide, doxorubicin, and fluorouracil IV on days 1 every 21 days for 4 courses
  • Doxorubicin every 21 days for 4 courses followed by CMF comprising cyclophosphamide IV, methotrexate IV, and fluorouracil IV on days 1 and 8 every 28 days for 4 courses
  • AC OR EC and paclitaxel IV with filgrastim (G-CSF) every 14 days for 4 courses
  • FEC comprising cyclophosphamide IV, epirubicin IV and fluorouracil IV on day 1 every 21 days for 3 courses followed by docetaxel IV on day 1 every 21 days for 3 courses
  • TAC comprising docetaxel, doxorubicin, and cyclophosphamide IV on day 1 every 21 days for 6 courses
  • AT comprising doxorubicin IV and docetaxel IV every 21 days for 3 courses followed by CMF for 3 courses
• Arm II: Patients receive adjuvant induction chemotherapy as in arm I. Beginning within 56 days after the first day of the last course of induction chemotherapy, patients receive CM (maintenance chemotherapy) comprising oral cyclophosphamide once daily and oral methotrexate two times a day twice weekly for 1 year.

Patients with breast-conserving surgery receive radiotherapy following completion of induction chemotherapy.

Patients with HER2-positive primary breast cancer may also receive trastuzumab (Herceptin) during or following induction, and/or during and following CM.

Quality of life is assessed at baseline, at the beginning of each course of induction chemotherapy, and at months 9, 12, 18, and 24.

Patients are followed every 6 months for 5 years and then annually thereafter.

Trial Contact Information

Trial Lead Organizations

International Breast Cancer Study Group

Marco Colleoni, MD, Protocol chair		Ph: 39-2-5748-9502

Australia
	Christchurch
	Christchurch Hospital
		ANZ BCTG Operations Office - Department of Surgical Oncology	Ph:  61-2-4985-0166
New South Wales
	Tweed Heads
	Tweed Heads Hospital
		ANZ BCTG Operations Office - Department of Surgical Oncology	Ph:  61-2-4985-0166
South Australia
	Adelaide
	Queen Elizabeth Hospital
		ANZ BCTG Operations Office - Department of Surgical Oncology	Ph:  61-2-4985-0166
Victoria
	Box Hill
	Box Hill Hospital
		ANZ BCTG Operations Office - Department of Surgical Oncology	Ph:  61-2-4985-0166
	East Ringwood
	Maroondah Hospital
		ANZ BCTG Operations Office - Department of Surgical Oncology	Ph:  61-2-4985-0166
	Wodonga
	Murray Valley Private Hospital and Cancer Treatment Centre
		ANZ BCTG Operations Office - Department of Surgical Oncology	Ph:  61-2-4985-0166
Belgium
	Liege
	CHU Liege - Domaine Universitaire du Sart Tilman
		Guy Jerusalem, MD, PhD	Ph:  32-4-366-7111
			Email: g.jerusalem@chu.ulg.ac.be
Brazil
Rio Grande do Sul
	Porto Alegre
	Hospital de Clinicas de Porto Alegre
		Carlos Menke, MD, PhD	Ph:  55-51-2101-8232
			Email: menke@hcpa.ufrgs.br
Chile
	Santiago
	Centro de Estudios Oncologicos Santiago
		Majlis Alejandro, MD	Ph:  56-2-201-9661
	Fundacion Arturo Lopez Perez
		Alejandro Majlis, MD	Ph:  56-2-421-8596
	Hospital Clinico San Borja Arriaran
		Cesar Del Castillo	Ph:  56-2-544-6628
	Hospital Clinico Universidad de Chile
		Mahave, MD	Ph:  56-2-978-8974
	Valparaiso
	Hospital Carlos Van Buren
		Alejandro Acevedo	Ph:  56-32-204-256
Hungary
	Budapest
	National Institute of Oncology
		Istvan Lang, MD, PhD, DSc	Ph:  36-1-22-48-763
			Email: lang@oncol.hu
Italy
	Bergamo
	Ospedali Riuniti di Bergamo
		Carlo Tondini, MD	Ph:  39-03-526-6424
			Email: carlo.tondoni@ospedaliriuniti.bergamo.it
	Biella
	Ospedale degli Infermi - ASL 12
		Mario Clerico, MD	Ph:  39-15-350-3705
			Email: mario.clerico@asl12.piemonte.it
	Carpi
	Ospedale Civile Ramazzini
		Fabrizio Artioli, MD	Ph:  39-059-659-313
			Email: f.artioli@ausl.mo.it
	Lecco
	Ospedale Alessandro Manzoni
		Giovanni Ucci, MD	Ph:  39-341-489-900
			Email: g.ucci@ospedale.lecco.it
	Milan
	Ospedale San Paolo
		Paolo Foa, MD	Ph:  39-02-5032-3085
	Milano
	European Institute of Oncology
		Marco Colleoni, MD	Ph:  39-2-5748-9502
	Padova
	Azienda Ospedaliera di Padova
		Silvio Monfardini, MD	Ph:  39-49-821-5931
			Email: silvio.monfardini@unipd.it
	Rimini
	Ospedale Civile Rimini
		Alberto Ravaioli, MD	Ph:  39-541-705-409
			Email: aravaiol@auslrn.net
	Rome
	Ospedale Sant' Eugenio
		Mauro Antimi, MD	Ph:  39-06-5100-2569
			Email: mauro.antimi@alsrmc.it
	Udine
	Policlinico Universitario Udine
		Fabio Puglisi	Ph:  39-4-3255-9304
			Email: fabio.puglisi@med.uniud.it
Nigeria
	Ibadan
	University of Ibadan Health Center
		Contact Person	Ph:  234-2-241-0995
Peru
	Lima
	Instituto Nacional de Enfermedades Neoplasicas
		Henry Gomez, MD	Ph:  51-1-271-1143
			Email: gomezhenry@terra.com.pe
Republic of South Africa
	Johannesburg
	Sandton Oncology Centre
		Daniel Vorobiof, MD	Ph:  27-11-883-0900
			Email: voro@global.co.za
Romania
	Cluj-Napoca
	Institutul Oncologic - Universitatea de Medicina
		Contact Person	Ph:  40-64-197-692
Switzerland
	Aarau
	Kantonspital Aarau
		Astrid Schonenberger, MD	Ph:  41-62-838-6053
	Bellinzona
	Oncology Institute of Southern Switzerland
		Olivia Pagani, MD	Ph:  41-91-820-9111
			Email: olivia.pagani@ibcsg.org
	Bern
	Inselspital Bern
		Stefan Aebi, MD	Ph:  41-31-632-4114
			Email: stefan.aebi@insel.ch
	Chur
	Kantonsspital Graubuenden
		Roger von Moos, MD	Ph:  41-81-256-6644
			Email: roger.vonmoos@ksgr.ch
	Rheinfelden
	FMH Onkologie/Haematologie
		Beretta Kurt, MD	Ph:  41-61-836-9393
	St. Gallen
	Kantonsspital - St. Gallen
		Beat Thurlimann, MD	Ph:  41-7-1494-1111
			Email: beat.thuerlimann@kssg.ch
	Thun
	Regionalspital
		Jean Marc Luthi, MD	Ph:  41-3-3226-2645
	Zurich
	UniversitaetsSpital Zuerich
		Bernhard Pestalozzi, MD	Ph:  41-44-255-2214

Registry Information
Official Title		Maintenance Chemotherapy In Hormone Non-Responsive Breast Cancer, Assessment of Vascular Endothelial Growth Factor (VEGF), Soluble Her2 Protein (NRP, HER2-ECD) and Vascular Cellular Adhesion Molecule-1 (VCAM-1) in Serum Samples
Trial Start Date		2000-11-22
Registered in ClinicalTrials.gov		NCT00022516
Date Submitted to PDQ		2001-06-22
Information Last Verified		2008-09-03

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