Combination Chemotherapy With or Without Trastuzumab in Treating Women With Breast Cancer
18. juli 2013 oppdatert av: UNICANCER
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
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).
Studieoversikt
Status
Fullført
Forhold
Intervensjon / Behandling
Detaljert beskrivelse
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.
Studietype
Intervensjonell
Registrering (Faktiske)
3010
Fase
- Fase 3
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
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Angers, Frankrike, 49036
- Centre Paul Papin
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Annecy, Frankrike, 74011 Cedex
- Centre hospitalier d'Annecy
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Bordeaux, Frankrike, 33076
- Institut Bergonie
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Bourg En Bresse, Frankrike, 01012
- C.H. Bourg En Bresse
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Caen, Frankrike, 14076
- Centre Regional Francois Baclesse
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Clermont-Ferrand, Frankrike, 63011
- Centre Jean Perrin
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Creteil, Frankrike, 94010
- Hôpital Intercommunal de Créteil
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Dijon, Frankrike, 21079
- Centre de Lutte Contre le Cancer Georges-Francois Leclerc
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Grenoble, Frankrike, 38100
- Institut Prive de Cancerologie
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Harfleur, Frankrike, 76700
- Clinique du Petit Colmouilins
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Lagny Sur Marne, Frankrike, 77405
- Centre Hospitalier de Lagny
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Le Chesnay, Frankrike, 78157
- Hôpital André Mignot
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Le Havre, Frankrike, 76600
- CMC Les Ormeaux
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Marseille, Frankrike, 13273
- Institut J. Paoli and I. Calmettes
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Metz, Frankrike, 57038
- Centre Hospitalier Régional Metz Thionville
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Montbeliard, Frankrike, 25209
- Centre Hospitalier General Andre Boulloche
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Montpellier, Frankrike, 34298
- Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
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Mulhouse, Frankrike, 68051
- Centre Hospitalier de Mulhouse
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Nantes-Saint Herblain, Frankrike, 44805
- Centre Regional Rene Gauducheau
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Paris, Frankrike, 75674
- Hopital Avicenne
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Perpignan, Frankrike
- Clinique Saint - Pierre
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Poitiers, Frankrike, 86021
- CHU Poitiers
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Reims, Frankrike, 51056
- Institut Jean Godinot
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Rennes, Frankrike, 35042
- Centre Eugene Marquis
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Sainte Clotilde, Frankrike, 97492
- Clinique sainte Clotilde
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Strasbourg, Frankrike, 67065
- Centre Paul Strauss
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Strasbourg, Frankrike, 67091
- Hopitaux Universitaire de Strasbourg
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Toulouse, Frankrike, 31052
- Institut Claudius Regaud
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Villejuif, Frankrike, F-94805
- Institut Gustave Roussy
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Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
18 år til 64 år (Voksen)
Tar imot friske frivillige
Nei
Kjønn som er kvalifisert for studier
Hunn
Beskrivelse
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
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Aktiv komparator: 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.
|
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)
Andre navn:
500 mg/m², D1 and every 3 weeks
100 mg/m², D1 and every 3 weeks
Andre navn:
500 mg/m², D1 and every 3 weeks
|
|
Eksperimentell: 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
|
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)
Andre navn:
100 mg/m², D1 and every 3 weeks
Andre navn:
on day D1 of each cycle : dose: 75 mg/m², route: i.v.
injection over 1 hour, every 3 weeks
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tidsramme |
|---|---|
|
Progression Free Survival
Tidsramme: 5 years from randomization
|
5 years from randomization
|
Sekundære resultatmål
Resultatmål |
Tidsramme |
|---|---|
|
Herceptin safety
Tidsramme: 5 years from randomization
|
5 years from randomization
|
|
Overall survival
Tidsramme: 5 years from randomization
|
5 years from randomization
|
Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
Etterforskere
- Studiestol: Marc Spielmann, MD, Gustave Roussy, Cancer Campus, Grand Paris
Publikasjoner og nyttige lenker
Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.
Generelle publikasjoner
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart
1. juni 2001
Primær fullføring (Faktiske)
1. juni 2009
Studiet fullført (Faktiske)
1. desember 2009
Datoer for studieregistrering
Først innsendt
5. februar 2003
Først innsendt som oppfylte QC-kriteriene
5. februar 2003
Først lagt ut (Anslag)
6. februar 2003
Oppdateringer av studieposter
Sist oppdatering lagt ut (Anslag)
19. juli 2013
Siste oppdatering sendt inn som oppfylte QC-kriteriene
18. juli 2013
Sist bekreftet
1. juli 2013
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
- Hudsykdommer
- Neoplasmer
- Neoplasmer etter nettsted
- Bryst sykdommer
- Brystneoplasmer
- Fysiologiske effekter av legemidler
- Molekylære mekanismer for farmakologisk virkning
- Enzymhemmere
- Antirevmatiske midler
- Antimetabolitter, antineoplastisk
- Antimetabolitter
- Antineoplastiske midler
- Immunsuppressive midler
- Immunologiske faktorer
- Tubulin modulatorer
- Antimitotiske midler
- Mitosemodulatorer
- Antineoplastiske midler, Alkylering
- Alkyleringsmidler
- Myeloablative agonister
- Topoisomerase II-hemmere
- Topoisomerasehemmere
- Antineoplastiske midler, immunologiske
- Antibiotika, antineoplastisk
- Docetaxel
- Cyklofosfamid
- Trastuzumab
- Fluorouracil
- Epirubicin
Andre studie-ID-numre
- UC-0140/0005 - PACS 04
- FRE-FNCLCC-PACS-04/0005
- EU-20236
- PACS04 (Annen identifikator: UNICANCER)
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .