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

NCT ID: NCT00054587

Last Updated: 2013-07-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 3010 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-06-30
• Study Completion Date: 2009-12-31

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).

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.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Trastuzumab

Intervention Type: BIOLOGICAL

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)

Cyclophosphamide

Intervention Type: DRUG

500 mg/m², D1 and every 3 weeks

Epirubicin

Intervention Type: DRUG

100 mg/m², D1 and every 3 weeks

Fluorouracil

Intervention Type: DRUG

500 mg/m², D1 and every 3 weeks

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

Group Type: EXPERIMENTAL

Trastuzumab

Intervention Type: BIOLOGICAL

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)

docetaxel

Intervention Type: DRUG

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

Epirubicin

Intervention Type: DRUG

100 mg/m², D1 and every 3 weeks

Interventions

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)

Intervention Type: BIOLOGICAL

Cyclophosphamide

500 mg/m², D1 and every 3 weeks

Intervention Type: DRUG

docetaxel

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

Intervention Type: DRUG

Epirubicin

100 mg/m², D1 and every 3 weeks

Intervention Type: DRUG

Fluorouracil

500 mg/m², D1 and every 3 weeks

Intervention Type: DRUG

Other Intervention Names

Herceptin; epirubicin hydrochloride

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

UNICANCER

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marc Spielmann, MD

Role: STUDY_CHAIR

Gustave Roussy, Cancer Campus, Grand Paris

Locations

Centre Paul Papin

Angers, , France

Centre Hospitalier d'Annecy

Annecy, , France

Institut Bergonie

Bordeaux, , France

C.H. Bourg En Bresse

Bourg-en-Bresse, , France

Centre Regional Francois Baclesse

Caen, , France

Centre Jean Perrin

Clermont-Ferrand, , France

Hopital Intercommunal De Creteil

Créteil, , France

Centre de Lutte Contre le Cancer Georges-Francois Leclerc

Dijon, , France

Institut Prive de Cancerologie

Grenoble, , France

Clinique du Petit Colmouilins

Harfleur, , France

Centre Hospitalier de Lagny

Lagny-sur-Marne, , France

Hopital Andre Mignot

Le Chesnay, , France

CMC Les Ormeaux

Le Havre, , France

Institut J. Paoli and I. Calmettes

Marseille, , France

Centre Hospitalier Regional Metz Thionville

Metz, , France

Centre Hospitalier General Andre Boulloche

Montbéliard, , France

Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle

Montpellier, , France

Centre Hospitalier de Mulhouse

Mulhouse, , France

Centre Regional Rene Gauducheau

Nantes-Saint Herblain, , France

Hopital Avicenne

Paris, , France

Clinique Saint - Pierre

Perpignan, , France

CHU Poitiers

Poitiers, , France

Institut Jean Godinot

Reims, , France

Centre Eugene Marquis

Rennes, , France

Clinique Sainte Clotilde

Sainte Clotilde, , France

Centre Paul Strauss

Strasbourg, , France

Hopitaux Universitaire de Strasbourg

Strasbourg, , France

Institut Claudius Regaud

Toulouse, , France

Institut Gustave Roussy

Villejuif, , France

Countries

France

References

Mancini J, Genre D, Dalenc F, Maylevin F, Martin AL, Viens P, Julian-Reynier C. Transparency in the presentation of trial results may not increase patients' trust in medical researchers. Clin Trials. 2012 Feb;9(1):90-3. doi: 10.1177/1740774511427063. Epub 2011 Nov 2.

Reference Type: BACKGROUND

PMID: 22049088 (View on PubMed)

Roché H, Allouache D, Romieu G, et al.: Five-year analysis of the FNCLCC-PACS04 trial: FEC100 vs ED75 for the adjuvant treatment of node positive breast cancer. [Abstract] 32nd Annual San Antonio Breast Cancer Symposium, December 9-13, 2009, San Antonio, Texas. A-602, 2009.

Reference Type: RESULT

Spielmann M, Roche H, Delozier T, Canon JL, Romieu G, Bourgeois H, Extra JM, Serin D, Kerbrat P, Machiels JP, Lortholary A, Orfeuvre H, Campone M, Hardy-Bessard AC, Coudert B, Maerevoet M, Piot G, Kramar A, Martin AL, Penault-Llorca F. Trastuzumab for patients with axillary-node-positive breast cancer: results of the FNCLCC-PACS 04 trial. J Clin Oncol. 2009 Dec 20;27(36):6129-34. doi: 10.1200/JCO.2009.23.0946. Epub 2009 Nov 16.

Reference Type: RESULT

PMID: 19917839 (View on PubMed)

Spielmann M, Roché H, Humblet Y, et al.: 3-year follow-up of trastuzumab following adjuvant chemotherapy in node positive HER2-positive breast cancer patients: results of the PACS-04 trial. [Abstract] Breast Cancer Res Treat 106 (1): A-72, S19, 2007.

Reference Type: RESULT

Spielmann M, Roché H, Delozier T, et al.: Safety analysis from PACS 04--a phase III trial comparing 6 cycles of FEC100 with 6 cycles of ET75 for node-positive early breast cancer patients, followed by sequential trastuzumab in HER2+patients: preliminary results. [Abstract] J Clin Oncol 24 (Suppl 18): A-632, 2006.

Reference Type: RESULT

O'Sullivan CC, Bradbury I, Campbell C, Spielmann M, Perez EA, Joensuu H, Costantino JP, Delaloge S, Rastogi P, Zardavas D, Ballman KV, Holmes E, de Azambuja E, Piccart-Gebhart M, Zujewski JA, Gelber RD. Efficacy of Adjuvant Trastuzumab for Patients With Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer and Tumors </= 2 cm: A Meta-Analysis of the Randomized Trastuzumab Trials. J Clin Oncol. 2015 Aug 20;33(24):2600-8. doi: 10.1200/JCO.2015.60.8620. Epub 2015 Jun 22.

Reference Type: DERIVED

PMID: 26101239 (View on PubMed)

Other Identifiers

FRE-FNCLCC-PACS-04/0005

Identifier Type: -

Identifier Source: secondary_id

EU-20236

Identifier Type: -

Identifier Source: secondary_id

PACS04

Identifier Type: OTHER

Identifier Source: secondary_id

UC-0140/0005 - PACS 04

Identifier Type: -

Identifier Source: org_study_id