Combination Chemotherapy With or Without Trastuzumab in Treating Women With Breast Cancer

Sponsor

UNICANCER (Other)

Overall Status

Completed

CT.gov ID

NCT00054587

Collaborator

(none)

3,010

Enrollment

Locations

Arms

102

Duration (Months)

103.8

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known which regimen of chemotherapy plus radiation therapy with or without trastuzumab is more effective in treating breast cancer.

PURPOSE: Randomized phase III trial to compare two different chemotherapy regimens plus radiation therapy with or without trastuzumab in treating women who have breast cancer that has spread to lymph nodes in the axilla (under the arm).

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Biological: Trastuzumab Drug: Cyclophosphamide Drug: docetaxel Drug: Epirubicin Drug: Fluorouracil	Phase 3

Detailed Description

OBJECTIVES:

Compare the efficacy of adjuvant cyclophosphamide, epirubicin, and fluorouracil vs adjuvant docetaxel and epirubicin, in terms of 5-year survival without relapse, in women with nonmetastatic adenocarcinoma of the breast with lymph node invasion.
Determine survival of patients treated with these regimens.
Compare the tolerability of trastuzumab (Herceptin) in patients treated with these regimens.
Determine the efficacy and tolerability of trastuzumab in patients with hormone receptor-positive tumors.
Evaluate the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to participating center. Patients are treated in 2 parts.

Part I: Patients are randomized to 1 of 2 treatment arms.
Arm I: Patients receive fluorouracil IV, or epirubicin IV, and cyclophosphamide IV on day 1. Treatment repeats every 3 weeks for 6 courses. Patients then undergo radiotherapy 5 days a week for 5 weeks.
Arm II: Patients receive epirubicin IV over 10 minutes and docetaxel IV over 1 hour on day 1. Treatment repeats every 3 weeks for 6 courses. Patients then undergo radiotherapy as in arm I.

Patients with HER2/neu-positive tumors then proceed to part II. Patients with HER2/neu-negative tumors receive no further treatment.

Patients with hormone (estrogen or progesterone) receptor-positive tumors also receive oral tamoxifen daily beginning after chemotherapy is completed and continuing for 5 years.

Part II: Patients are randomized to 1 of 2 treatment arms.
Arm I: Patients receive trastuzumab (Herceptin) IV over 30-90 minutes every 3 weeks for 1 year.
Arm II: Patients are followed without treatment. Patients not receiving trastuzumab are followed at 4 months, 6 months, every 4 months for 1 year, and then every 6 months for 3 years. Patients receiving trastuzumab are followed at 4 months and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 2,600 patients will be accrued for this study within 3 years.

Study Design

Study Type:

Interventional

Actual Enrollment :

3010 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Randomized And Multicentric Opened Phase III Study Evaluating The Concomitant Administration Of Docetaxel 75MG/M2 and Epirubicine 75MG/M2 Versus FEC 100 In Non Metastatic With Positive Lymphatic Nodes Breast Cancer Subjects, And The Sequential Addition Of Herceptin In (HER2+++) And (HER2++ And FISH+) Subjects

Study Start Date :

Jun 1, 2001

Actual Primary Completion Date :

Jun 1, 2009

Actual Study Completion Date :

Dec 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 6 FEC Patients receive fluorouracil IV, or epirubicin IV, and cyclophosphamide IV on day 1. Treatment repeats every 3 weeks for 6 courses. Patients then undergo radiotherapy 5 days a week for 5 weeks.	Biological: Trastuzumab 8 mg/kg at month M6, followed by a maintenance dose of 6 mg/kg every 3 weeks for a 1 year (i.e. 18 injections in total) Other Names: Herceptin Drug: Cyclophosphamide 500 mg/m², D1 and every 3 weeks Drug: Epirubicin 100 mg/m², D1 and every 3 weeks Other Names: epirubicin hydrochloride Drug: Fluorouracil 500 mg/m², D1 and every 3 weeks
Experimental: 6 DE Patients receive epirubicin IV over 10 minutes and docetaxel IV over 1 hour on day 1. Treatment repeats every 3 weeks for 6 courses. Patients then undergo radiotherapy as in arm I	Biological: Trastuzumab 8 mg/kg at month M6, followed by a maintenance dose of 6 mg/kg every 3 weeks for a 1 year (i.e. 18 injections in total) Other Names: Herceptin Drug: docetaxel on day D1 of each cycle : dose: 75 mg/m², route: i.v. injection over 1 hour, every 3 weeks Drug: Epirubicin 100 mg/m², D1 and every 3 weeks Other Names: epirubicin hydrochloride

Arm

Intervention/Treatment

Active Comparator: 6 FEC

Patients receive fluorouracil IV, or epirubicin IV, and cyclophosphamide IV on day 1. Treatment repeats every 3 weeks for 6 courses. Patients then undergo radiotherapy 5 days a week for 5 weeks.

Biological: Trastuzumab

8 mg/kg at month M6, followed by a maintenance dose of 6 mg/kg every 3 weeks for a 1 year (i.e. 18 injections in total)

Other Names:

Herceptin

Drug: Cyclophosphamide

500 mg/m², D1 and every 3 weeks

Drug: Epirubicin

100 mg/m², D1 and every 3 weeks

Other Names:

epirubicin hydrochloride

Drug: Fluorouracil

500 mg/m², D1 and every 3 weeks

Experimental: 6 DE

Patients receive epirubicin IV over 10 minutes and docetaxel IV over 1 hour on day 1. Treatment repeats every 3 weeks for 6 courses. Patients then undergo radiotherapy as in arm I

Biological: Trastuzumab

8 mg/kg at month M6, followed by a maintenance dose of 6 mg/kg every 3 weeks for a 1 year (i.e. 18 injections in total)

Other Names:

Herceptin

Drug: docetaxel

on day D1 of each cycle : dose: 75 mg/m², route: i.v. injection over 1 hour, every 3 weeks

Drug: Epirubicin

100 mg/m², D1 and every 3 weeks

Other Names:

epirubicin hydrochloride

Outcome Measures

Primary Outcome Measures

Progression Free Survival [5 years from randomization]

Secondary Outcome Measures

Herceptin safety [5 years from randomization]
Overall survival [5 years from randomization]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 64 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed nonmetastatic, unilateral adenocarcinoma of the breast
Axillary lymph node invasion (N1, N2, or N3)
No cutaneous invasion
No T4a or greater disease
No clinically or radiologically suspected metastases
No clinically or radiologically suspected contralateral lesion
No deeply adherent or inflammatory disease
Complete surgical resection performed, including removal of at least 5 lymph nodes, and with no residual tumor, within the past 42 days
No prior breast cancer
Hormone receptor status:
Not specified

PATIENT CHARACTERISTICS:

Age

18 to 64

Sex

Female

Menopausal status

Not specified

Performance status

WHO 0-1

Life expectancy

Not specified

Hematopoietic

WBC at least 2,000/mm^3
Platelet count at least 100,000/mm^3

Hepatic

ALT and AST no greater than 1.5 times upper limit of normal (ULN)
Alkaline phosphatase no greater than 2.5 times ULN
Bilirubin no greater than ULN
Hepatitis B and hepatitis C negative
No hepatic dysfunction

Renal

Creatinine less than 1.3 mg/dL OR
Creatinine clearance greater than 60 mL/min

Cardiovascular

ECHO normal
LVEF at least 50%

Pulmonary

FEV normal
No dyspnea at rest
No supplemental oxygen dependence

Other

Not pregnant
Fertile patients must use effective contraception
HIV negative
No active infection
No other prior malignancy except basal cell skin cancer or carcinoma in situ of the cervix
No contraindication to anthracycline therapy
No chronic medical or psychological condition
No geographic or social reason that would preclude study therapy

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

At least 4 weeks since prior chemotherapy
No other concurrent chemotherapy
No contraindication to anthracycline therapy

Endocrine therapy

No prior hormonal therapy

Radiotherapy

No prior radiotherapy

Surgery

See Disease Characteristics

Other

At least 4 weeks since prior experimental 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	Institut Bergonie	Bordeaux	France	33076
4	C.H. Bourg En Bresse	Bourg En Bresse	France	01012
5	Centre Regional Francois Baclesse	Caen	France	14076
6	Centre Jean Perrin	Clermont-Ferrand	France	63011
7	Hopital Intercommunal De Creteil	Creteil	France	94010
8	Centre de Lutte Contre le Cancer Georges-Francois Leclerc	Dijon	France	21079
9	Institut Prive de Cancerologie	Grenoble	France	38100
10	Clinique du Petit Colmouilins	Harfleur	France	76700
11	Centre Hospitalier de Lagny	Lagny Sur Marne	France	77405
12	Hopital Andre Mignot	Le Chesnay	France	78157
13	CMC Les Ormeaux	Le Havre	France	76600
14	Institut J. Paoli and I. Calmettes	Marseille	France	13273
15	Centre Hospitalier Regional Metz Thionville	Metz	France	57038
16	Centre Hospitalier General Andre Boulloche	Montbeliard	France	25209
17	Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle	Montpellier	France	34298
18	Centre Hospitalier de Mulhouse	Mulhouse	France	68051
19	Centre Regional Rene Gauducheau	Nantes-Saint Herblain	France	44805
20	Hopital Avicenne	Paris	France	75674
21	Clinique Saint - Pierre	Perpignan	France
22	CHU Poitiers	Poitiers	France	86021
23	Institut Jean Godinot	Reims	France	51056
24	Centre Eugene Marquis	Rennes	France	35042
25	Clinique Sainte Clotilde	Sainte Clotilde	France	97492
26	Centre Paul Strauss	Strasbourg	France	67065
27	Hopitaux Universitaire de Strasbourg	Strasbourg	France	67091
28	Institut Claudius Regaud	Toulouse	France	31052
29	Institut Gustave Roussy	Villejuif	France	F-94805