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

Alternate Title

Trastuzumab for 6 Months or 1 Year in Treating Women With Nonmetastatic Breast Cancer That Can Be Removed By Surgery

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Active	18 and over	Other	INCA-PHARE PHARE, INCA-RECF0146, EUDRACT-2006-000070-67, NCT00381901

Objectives

Primary

1. Compare the disease-free survival of women with nonmetastatic, resectable breast cancer treated with adjuvant trastuzumab (Herceptin®) for 6 months vs 12 months.

Secondary

1. Compare cardiotoxicity in patients receiving these regimens.
2. Compare the cardiotoxicity and disease-free survival of patients receiving concurrent trastuzumab and chemotherapy vs sequential administration.
3. Correlate HER-2 polymorphism with disease-free survival/cardiotoxicity in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed adenocarcinoma of the breast



• Nonmetastatic disease
  • Positive or negative axillary nodes
  • Tumor size ≥ 10 mm



• Resectable disease



• Must have received ≥ 4 courses of chemotherapy for this disease



• A 12-month adjuvant treatment with trastuzumab (Herceptin®) has been initiated
  • Informed consent form must be signed between the third and sixth months of trastuzumab therapy



• Overexpression of HER-2 in the invasive component of the primary tumor as indicated by 1 of the following:
  • 3+ by immunohistochemistry (IHC)
  • 2+ by IHC and confirmation by fluorescent in situ hybridization (FISH) or chromogenic in situ hybridization (CISH)



• Hormone receptor status not specified

Prior/Concurrent Therapy:

• See Disease Characteristics
• Other prior anti-HER-2 therapy allowed
• No prior trastuzumab other than initiation of trastuzumab adjuvant therapy

Patient Characteristics:

• Female
• Menopausal status not specified
• LVEF considered favorable for continuing trastuzumab treatment as measured by echocardiography or MUGA at 2-4 months after beginning adjuvant trastuzumab
• No serious cardiac illness or medical condition precluding trastuzumab treatment, including any of the following:
  • History of documented congestive heart failure
  • High-risk uncontrolled arrhythmias
  • Angina pectoris requiring antianginal medication
  • Severe dyspnea at rest or oxygen-dependent
• No known hypersensitivity to trastuzumab, murine proteins, or any of the excipients
• Not pregnant or nursing
• No social, geographical, or psychological condition that would preclude study participation

Expected Enrollment

A total of 7,000 patients will be accrued for this study.

Outcomes

Time to recurrence

Cardiotoxicity as measured by LVEF
Distant metastasis-free survival
Overall survival

Outline

This is a randomized, controlled, multicenter study. Patients are stratified according to participating center, modality of adjuvant chemotherapy (concurrent vs sequential), and adjuvant hormonal therapy (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I (control arm, 12-month therapy): Patients continue to receive trastuzumab (Herceptin®) IV until a total of 12 months of therapy is completed in the absence of disease progression or unacceptable toxicity.



• Arm II (experimental arm, 6-month therapy): Patients continue to receive trastuzumab* IV until a total of 6 months of therapy is completed in the absence of disease progression or unacceptable toxicity.

   [Note: *Patients who have already finished 6 months of trastuzumab at randomization do not receive further trastuzumab.]

Some patients undergo blood collection for HER-2 polymorphism analysis.

After completion of study therapy, patients are followed periodically for approximately 5 years.

Trial Contact Information

Trial Lead Organizations

Institut National du Cancer

Xavier Pivot, MD, PhD, Protocol chair		Ph: 33-3-8166-9386 Email: xpivot@chu-besancon.fr

France
	Angers
	Centre Paul Papin
		Sophie Abadie-Lacourtoisie, MD	Ph:  33-24-135-2734
	Annecy
	Centre Hospitalier d'Annecy
		Jocelyne Provencal, MD	Ph:  33-50-88-33-28
			Email: jprovencal@ch-annecy.fr
	Antibes
	Centre Hospitalier La Fontonne
		Jean-Francois Dor, MD	Ph:  33-4-9291-7735
	Argenteuil
	Centre Hospitalier Victor Dupouy
		Marine Gross-Goupil, MD	Ph:  33-1-3423-2425
	Aulnay Sous Bois
	Centre Hospital General Robert Ballanger
		Ghania Sadki-Benaoudia, MD	Ph:  33-1-4936-7141
	Avignon
	Institut Sainte Catherine
		Daniel Serin, MD	Ph:  33-490-276-263
			Email: d.serin@isc84.org
	Beauvais
	C.H.G. Beauvais
		Suzanne Nguyen, MD	Ph:  33-34-411-2309
			Email: s.nguyen@ch-beauvais.fr
	Besancon
	Centre Hospitalier Regional de Besancon - Hopital Jean Minjoz
		Xavier Pivot, MD, PhD	Ph:  33-3-8166-9386
			Email: xpivot@chu-besancon.fr
	Bobigny
	Hopital Avicenne
		Jean-Luc Breau, MD, PhD	Ph:  33-48-955-131
	Bordeaux
	Clinique Tivoli
		Dominique Jaubert, MD	Ph:  33-556-116-087
			Email: dominique.jaubert@wanadoo.fr
	Institut Bergonie
		Louis Mauriac, MD	Ph:  33-56-333-258
			Email: mauriac@bergonie.org
	Polyclinique Bordeaux Nord Aquitaine
		Nadine Dohollou, MD	Ph:  33-5-56-43-73-54
	Boulogne Sur Mer
	Centre Hospitalier Docteur Duchenne
		Zoher Merad-Boudia	Ph:  33-3-2199-3013
	Brest
	C.H.U. de Brest
		Nacr-Eddine Achour, MD	Ph:  33-2-9831-3200
	Brive
	Centre Hospitalier General
		Bernard Leduc, MD	Ph:  33-55-592-6000
			Email: oncologie@ch-brive.fr
	Chalon-sur-Saone
	Centre Hospitalier William Morey
		Bruno Salles, MD	Ph:  33-3-8544-6688
	Chartres
	Clinique Notre Dame du Bon Secours
		Marie Gasowski, MD	Ph:  33-2-3720-1515
	Hopital Louis Pasteur
		Elizabeth Angellier, MD, PhD	Ph:  33-2-3730-3077
	Clamart
	Hopital Antoine Beclere
		Francois Boue, MD, PhD	Ph:  33-1-45370160
			Email: francois.boue@abc.ap-hop-paris.fr
	Clermont-Ferrand
	Centre Jean Perrin
		Philippe Chollet, MD, PhD	Ph:  33-4-7327-8198
			Email: philippe.chollet@cjp.fr
	Colmar
	Hopital Louis Pasteur
		Bruno Audhuy, MD	Ph:  33-3-8912-4102
			Email: bruno.audhuy@ch-colmar.rss.fr
	Dax
	Centre Hospitalier de Dax
		Laure Gautier-Felizot	Ph:  33-6-8591-9735
	Dijon
	Centre de Lutte Contre le Cancer Georges-Francois Leclerc
		Pierre Fumoleau, MD, PhD	Ph:  33-3-8073-7506
	Epinal
	Hopital Jean Monnet
		Stephane Ruck, MD	Ph:  33-3-2968-7020
	Fort de France Cedex
	Hopital Clarac
		Patrick Escarmant, MD	Ph:  33-5-9655-2200
	Grenoble
	Institut Prive de Cancerologie
		David Coeffic, MD	Ph:  33-4-7633-5550
			Email: dcoeffic@club-internet.fr
	Hyeres
	Clinique Sainte-Marguerite
		Jean-Louis Wendling, MD	Ph:  33-4-94-12-55-60
			Email: jlwendling@aol.com
	La Garenne Colombes
	Centre De Radiotherapie Charlebourg
		Gerard Auclerc, MD	Ph:  33-1-4782-4695
	La Roche Sur Yon
	Centre Hospitalier Departemental
		Franck Priou, MD	Ph:  33-2-5144-6161
			Email: frank.priou@chd-vendee.fr
	Lagny Sur Marne
	Centre Hospitalier de Lagny
		Caroline Toussaint-Batbedat, MD	Ph:  33-1-6430-7070
	Le Chesnay
	Hopital Andre Mignot
		Didier Mayeur, MD	Ph:  33-1-3963-8909
			Email: dmayeur@ch-versailles.fr
	Le Mans
	Clinique Victor Hugo
		Gerard Ganem, MD	Ph:  33-2-4339-1300
	Levallois-Perret
	Institut d'Oncologie Hartmann
		Jean Francois Llory, MD	Ph:  33-1-4759-0000
			Email: jfllory@i-o-h.org
	Libourne
	Hopital Robert Boulin
		Nathalie Trufflandier, MD	Ph:  33-5-5755-3434
	Limoges
	Centre Hospital Regional Universitaire de Limoges
		Nicole Tubiana-Mathieu, MD	Ph:  33-5-5505-6123
			Email: oncologie@chu-limoges.fr
	Clinique Chenieux
		Xavier-Francois Zasadny, MD	Ph:  33-5-5545-4040
	Lyon
	Centre Leon Berard
		Jean Paul Guastalla, MD, PhD	Ph:  33-478-782-644
			Email: guastall@lyon.fnclcc.fr
	LYON
	Centre Medical Parot
		Alain Voloch, MD	Ph:  33-4-7894-2474
	Lyon
	Hopital Edouard Herriot - Lyon
		Jean-Yves Blay, MD, PhD	Ph:  33-47-211-7398
			Email: jy.blay@chu-lyon.fr
	Mareuil Les Meaux
	Centre de Radiotherapie et Oncologie Saint-Faron
		Jacques Mandet, MD	Ph:  33-16-43-34-848
			Email: jacques.mandet@wanadoo.fr
	Marseille
	Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes
		Carole Tarpin, MD	Ph:  33-49-122-3333
	Metz
	Hopital Clinique Claude Bernard
		Emmanuel Achille, MD	Ph:  33-3-8739-6735
	Meudon La Foret
	Centre de Radiologie et de Traitement des Tumeurs
		Eric Chirat, MD	Ph:  33-1-4632-0303
	Meulan
	CH Meulan
		Patricia Amsalhem, MD	Ph:  33-1-30-918-500
	Mont-de-Marsan
	Centre Hospitalier General de Mont de Marsan
		Jerome Dauba	Ph:  33-5-5805-1725
	Montelimar
	Centre Hospitalier de Montelimar
		Bertrand Mongodin, MD	Ph:  33-4-7553-4052
	Montlucon
	Centre Hospitalier de Montlucon
		Marie-Agnes Bichoffe, MD	Ph:  33-4-7008-3500
	Montpellier
	Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
		Gilles Romieu, MD	Ph:  33-4-67-613-151
	Clinique Clementville
		Stephane Jacquot, MD	Ph:  33-4-6706-7000
	Mougins
	Centre Azureen de Cancerologie
		Moise Namer, MD, PhD	Ph:  33-4-9292-3737
	Nantes
	Centre Catherine de Sienne
		Alain Lortholary, MD	Ph:  33-40-02-28-272-000
	Nantes-Saint-Herblain
	Centre Regional Rene Gauducheau
		Mario Campone, MD	Ph:  33-02-4067-9977
			Email: m-campone@nantes-fnclcc.fr
	Narbonne
	Clinique Les Genets
		Andre Mathieu, MD	Ph:  33-4-68-65-10-52
	Neuilly sur Seine
	Clinique Hartmann
		Eric-Charles Antoine, MD	Ph:  33-6-2203-1609
	Nice
	Centre Antoine Lacassagne
		Jean Marc Ferrero, MD	Ph:  33-4-9203-1114
			Email: jean-marc.ferrerero@nice.fnclcc.fr
	Clinique Belvedere
		Gerard Lesbats, MD	Ph:  33-4-9207-7575
	Clinique Saint George
		Michel Hoch	Ph:  33-49-362-6700
			Email: michel.hoch@wanadoo.fr
	Nimes
	C.H.U. de Nimes - Groupe Hospitals-Universitaire Caremeau
		Francois Bons, MD	Ph:  33-4-66-68-3163
	Clinique De Valdegour
		Jacques Cretin, MD	Ph:  33-46-662-58-02
	Paris
	CHU Pitie-Salpetriere
		David Khayat, MD, PhD	Ph:  33-1-42-160-476
			Email: david.khayat@psl.aphp.fr
	Hopital Europeen Georges Pompidou
		Eric Levy, MD	Ph:  33-1-5609-3473
	Hopital Saint-Louis
		Marc Espie, MD	Ph:  33-1-4249-9293
	Institut Curie Hopital
		Jean-Yves Pierga, MD, PhD	Ph:  33-1-4432-4672
	Pau
	Centre Hospitalier - Pau
		Nathalie Quenel-Tueux, MD	Ph:  33-5-5992-4848
	Perigueux
	Polyclinique Francheville
		Laurent Cany, MD	Ph:  33-553-064-140
			Email: l.cany@oncoradio24.com
	Perpignan
	Clinique Saint - Pierre
		Stephanie Catala, MD	Ph:  33-4-6855-7496
	Pierre Benite
	Centre Hospitalier Lyon Sud
		Veronique Trillet-Lenoir, MD	Ph:  33-78-863-324
			Email: veronique.trillet-lenoir@chu-lyon.fr
	Poissy
	Centre Hospitalier Intercommunal de Poissy
		Philippe Soyer, MD	Ph:  33-1-3927-4050
	Poitiers
	Hopital Jean Bernard
		Jean-Marc Tourani, MD	Ph:  33-549-444-534
			Email: jm.tourani@chu.poitiers.frs.fr
	Reims
	Institut Jean Godinot
		Christelle Jouannaud, MD	Ph:  33-3-2650-4403
	Rennes
	Centre Eugene Marquis
		Pierre Kerbrat, MD, PhD	Ph:  33-299-253-280
			Email: kerbrat@rennes.fnclcc.fr
	Roanne
	CHG Roanne
		Lionel Vincent, MD	Ph:  33-4-7744-3396
	Rouen
	Centre Henri Becquerel
		Emmanuel Blot, MD, PhD	Ph:  33-2-3208-2434
	Saint Brieuc
	Clinique Armoricaine De Radiologie
		Anne-Claire Hardy-Bessard, MD	Ph:  33-2-9675-2216
			Email: ac.hardy@clin-armoricaine.fr
	Saint Priest en Jarez
	Institut de Cancerologie de la Loire
		Guillaume Clavreul, MD	Ph:  33-47-742-1016
	Sainte Clotilde
	Clinique Sainte Clotilde
		Mickael Begue, MD	Ph:  33-2-6248-2040
	Saint-Nazaire
	Centre Etienne Dolet
		Valarie Delecroix, MD	Ph:  33-2-4053-8844
	Strasbourg
	Centre Paul Strauss
		Thierry Petit, MD, PhD	Ph:  33-3-8825-2424
			Email: tpetit@strasbourg.fnclcc.fr
	Clinique de l'Orangerie
		Francois Schaeffer, MD	Ph:  33-3-8814-1820
	Toulon - Cedex
	Centre Hospitalier Intercommunal Toulon - La Seyne Sur Mer
		Laurent Cals, MD	Ph:  33-4-94-61-60-52
			Email: Laurent.Cals@ch.toulon.fr
	Toulouse
	Institut Claudius Regaud
		Florence Dalenc, MD	Ph:  33-5-6142-4174
	Tours
	Centre Hospitalier Universitaire Bretonneau de Tours
		Philippe Bougnoux, MD, PhD	Ph:  33-2-4747-8261

Registry Information
Official Title		Protocol of Herceptin® Adjuvant with Reduced Exposure, a Randomised Comparison of 6 Months vs 12 months in all Women Receiving Adjuvant Herceptin® [PHARE]
Trial Start Date		2006-05-30
Registered in ClinicalTrials.gov		NCT00381901
Date Submitted to PDQ		2006-09-13
Information Last Verified		2008-12-28