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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00054587
• Other study ID #: UC-0140/0005 - PACS 04
• Secondary ID: FRE-FNCLCC-PACS-
• Status: Completed
• Phase: Phase 3
• First received: February 5, 2003
• Last updated: July 18, 2013
• Start date: June 2001
• Est. completion date: December 2009

Study information

• Verified date: July 2013
• Source: UNICANCER
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentFrance: Agence Nationale de Sécurité du Médicament et des produits de santé
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3010
• Est. completion date: December 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 64 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

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)

Drug:
• Cyclophosphamide
500 mg/m², D1 and every 3 weeks
• docetaxel
on day D1 of each cycle : dose: 75 mg/m², route: i.v. injection over 1 hour, every 3 weeks
• Epirubicin
100 mg/m², D1 and every 3 weeks
• Fluorouracil
500 mg/m², D1 and every 3 weeks

Locations

Country	Name	City	State
France	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	Creteil
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	Montbeliard
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

Sponsors (1)

Lead Sponsor	Collaborator
UNICANCER

Country where clinical trial is conducted

France, 

References & Publications (5)

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. — View Citation

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,

Spielmann M, Roché 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 pat — View Citation

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 r

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.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival		5 years from randomization	No
Secondary	Herceptin safety		5 years from randomization	Yes
Secondary	Overall survival		5 years from randomization	No