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

Sponsor

National Cancer Institute, France (Other)

Overall Status

Completed

CT.gov ID

NCT00381901

Collaborator

(none)

3,400

Enrollment

Locations

41.5

Patients Per Site

Study Details

Study Description

Brief Summary

RATIONALE: Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether giving trastuzumab for 6 months is as effective as giving trastuzumab for 1 year in treating patients with breast cancer.

PURPOSE: This randomized phase III trial is studying trastuzumab to see how well it works when given for 6 months compared to 12 months in treating women with nonmetastatic breast cancer that can be removed by surgery.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Biological: trastuzumab Genetic: polymorphism analysis Procedure: adjuvant therapy	Phase 3

Detailed Description

OBJECTIVES:

Primary

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

Secondary

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

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.

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

3400 participants

Allocation:

Randomized

Primary Purpose:

Treatment

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]

Study Start Date :

May 1, 2006

Actual Primary Completion Date :

May 1, 2011

Outcome Measures

Primary Outcome Measures

Time to recurrence []

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

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

PRIOR CONCURRENT THERAPY:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Centre Paul Papin	Angers	France	49036
2	Centre Hospitalier d'Annecy	Annecy	France	74011 Cedex
3	Centre Hospitalier La Fontonne	Antibes	France	06600
4	Centre Hospitalier Victor Dupouy	Argenteuil	France	95107
5	Centre Hospital General Robert Ballanger	Aulnay Sous Bois	France	93602
6	Institut Sainte Catherine	Avignon	France	84082
7	C.H.G. Beauvais	Beauvais	France	60021
8	Centre Hospitalier Regional de Besancon - Hopital Jean Minjoz	Besancon	France	25030
9	Hopital Avicenne	Bobigny	France	93009
10	Institut Bergonie	Bordeaux	France	33076
11	Polyclinique Bordeaux Nord Aquitaine	Bordeaux	France	33300
12	Clinique Tivoli	Bordeaux	France	F-33000
13	Centre Hospitalier Docteur Duchenne	Boulogne Sur Mer	France	62200
14	C.H.U. de Brest	Brest	France	29200
15	Centre Hospitalier General	Brive	France	19101
16	Centre Hospitalier William Morey	Chalon-sur-Saone	France	71100
17	Clinique Notre Dame du Bon Secours	Chartres	France	28000
18	Hopital Louis Pasteur	Chartres	France	28018
19	Hopital Antoine Beclere	Clamart	France	92141
20	Centre Jean Perrin	Clermont-Ferrand	France	63011
21	Hopital Louis Pasteur	Colmar	France	68024
22	Centre Hospitalier de Dax	Dax	France	40100
23	Centre de Lutte Contre le Cancer Georges-Francois Leclerc	Dijon	France	21079
24	Hopital Jean Monnet	Epinal	France	88021
25	Hopital Clarac	Fort de France Cedex	France	97261
26	Institut Prive de Cancerologie	Grenoble	France	38100
27	Clinique Sainte-Marguerite	Hyeres	France	83400
28	Centre De Radiotherapie Charlebourg	La Garenne Colombes	France	92250
29	Centre Hospitalier Departemental	La Roche Sur Yon	France	85025
30	Centre Hospitalier de Lagny	Lagny Sur Marne	France	77405
31	Hopital Andre Mignot	Le Chesnay	France	78157
32	Clinique Victor Hugo	Le Mans	France	F-72000
33	Institut d'Oncologie Hartmann	Levallois-Perret	France	92300
34	Hopital Robert Boulin	Libourne	France	33500
35	Clinique Chenieux	Limoges	France	87000
36	Centre Hospital Regional Universitaire de Limoges	Limoges	France	87042
37	Centre Medical Parot	Lyon	France	69006
38	Centre Leon Berard	Lyon	France	69373
39	Hopital Edouard Herriot - Lyon	Lyon	France	69437
40	Centre de Radiotherapie et Oncologie Saint-Faron	Mareuil Les Meaux	France	77100
41	Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes	Marseille	France	13273
42	Hopital Clinique Claude Bernard	Metz	France	57072
43	Centre de Radiologie et de Traitement des Tumeurs	Meudon La Foret	France	92360
44	CH Meulan	Meulan	France	78250
45	Centre Hospitalier General de Mont de Marsan	Mont-de-Marsan	France	40000
46	Centre Hospitalier de Montelimar	Montelimar	France	26200
47	Centre Hospitalier de Montlucon	Montlucon	France	03109
48	Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle	Montpellier	France	34298
49	Clinique Clementville	Montpellier	France
50	Centre Azureen de Cancerologie	Mougins	France	06250
51	Centre Regional Rene Gauducheau	Nantes-Saint-Herblain	France	44805
52	Centre Catherine de Sienne	Nantes	France	02
53	Clinique Les Genets	Narbonne	France	11100
54	Clinique Hartmann	Neuilly sur Seine	France	92200
55	Clinique Belvedere	Nice	France	06000
56	Clinique Saint George	Nice	France	06100
57	Centre Antoine Lacassagne	Nice	France	06189
58	C.H.U. de Nimes - Groupe Hospitals-Universitaire Caremeau	Nimes	France	30029
59	Clinique De Valdegour	Nimes	France	30900
60	Hopital Europeen Georges Pompidou	Paris	France	75015
61	Institut Curie Hopital	Paris	France	75248
62	Hopital Saint-Louis	Paris	France	75475
63	CHU Pitie-Salpetriere	Paris	France	75651
64	Centre Hospitalier - Pau	Pau	France	64046
65	Polyclinique Francheville	Perigueux	France	24004
66	Clinique Saint - Pierre	Perpignan	France
67	Centre Hospitalier Lyon Sud	Pierre Benite	France	69495
68	Centre Hospitalier Intercommunal de Poissy	Poissy	France	78300
69	Hopital Jean Bernard	Poitiers	France	86021
70	Institut Jean Godinot	Reims	France	51056
71	Centre Eugene Marquis	Rennes	France	35042
72	CHG Roanne	Roanne	France	F-42300
73	Centre Henri Becquerel	Rouen	France	76038
74	Clinique Armoricaine De Radiologie	Saint Brieuc	France	F-22015
75	Institut de Cancerologie de la Loire	Saint Priest en Jarez	France	42270
76	Centre Etienne Dolet	Saint-Nazaire	France	44600
77	Clinique Sainte Clotilde	Sainte Clotilde	France	97192
78	Clinique de l'Orangerie	Strasbourg	France	67010
79	Centre Paul Strauss	Strasbourg	France	67065
80	Centre Hospitalier Intercommunal Toulon - La Seyne Sur Mer	Toulon - Cedex	France	83056
81	Institut Claudius Regaud	Toulouse	France	31052
82	Centre Hospitalier Universitaire Bretonneau de Tours	Tours	France	37044