Safety and Efficacy Comparison of Docetaxel and Ixabepilone in Non Metastatic Poor Prognosis Breast Cancer

NCT ID: NCT00630032

Last Updated: 2024-02-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 762 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-09-30
• Study Completion Date: 2020-09-03

Brief Summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) and giving them after surgery may kill any tumor cells remaining after surgery. It is not yet known whether docetaxel is more effective than ixabepilone when given after surgery and combination chemotherapy in treating breast cancer.

PURPOSE: This randomized phase III trial is studying giving combination chemotherapy followed by docetaxel or ixabepilone to compare how well they work in treating patients who have undergone surgery for nonmetastatic breast cancer.

Detailed Description

OBJECTIVES:

Primary

• To evaluate the benefit from sequential administration of 3 courses of combination chemotherapy (FEC100) followed by 3 courses of ixabepilone versus docetaxel on the 5-year disease-free survival of women with nonmetastatic, poor-prognosis breast cancer.

Secondary

• To compare the 5-year distant metastasis-free survival.
• To compare the 5-year event-free survival.
• To compare the 5-year overall survival.
• To compare the safety profiles for the two chemotherapy regimens.
• To identify and/or validate predictive-gene expression profiles of clinical response/resistance to the two treatment regimens.
• To bank frozen and fixed tumor and frozen serum prospectively for future translational studies in both genomics and proteomics (transcriptome and proteome analyses, tissue array analyses).
• To compare the cost-effectiveness of these 2 regimens.
• To compare the quality-of-life of patients treated with these 2 regimens.

OUTLINE: This is a multicenter study. Patients are stratified according to participating center, menopausal status (pre- vs post-menopausal), and tumor hormone-receptor status (triple-negative vs progesterone-receptor negative, HER negative, and estrogen-receptor [ER] positive). Patients are randomized to 1 of 2 treatment arms.

• Docetaxel Arm: Patients receive epirubicin hydrochloride IV, fluorouracil IV, and cyclophosphamide IV every 3 weeks in courses 1-3 and docetaxel IV alone every 3 weeks in courses 4-6.
• Ixabepilone Arm: Patients receive treatment in courses 1-3 as in arm I and ixabepilone IV alone every 3 weeks in courses 4-6.

In both arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients also complete a quality of life questionnaire periodically.

After completion of study treatment, patients are followed periodically for up to 10 years.

Conditions

Breast Cancer

Study Design

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

Study Groups

Docetaxel

3 cycles of FEC100 (F and C, each at 500 mg/m², E 100 mg/m², every 3 weeks) followed by 3 cycles of D (100 mg/m² every 3 weeks)

Group Type: ACTIVE_COMPARATOR

cyclophosphamide

Intervention Type: DRUG

500 mg/m² every 3 weeks

Docetaxel

Intervention Type: DRUG

100 mg/m² every 3 weeks

epirubicin hydrochloride

Intervention Type: DRUG

100 mg/m² every 3 weeks

fluorouracil

Intervention Type: DRUG

500 mg/m² every 3 weeks

Ixabepilone

3 cycles of FEC100 (F and C, each at 500 mg/m², E 100 mg/m², every 3 weeks) followed by 3 cycles of Ixabepilone (40 mg/m² every 3 weeks);

Group Type: EXPERIMENTAL

cyclophosphamide

Intervention Type: DRUG

500 mg/m² every 3 weeks

epirubicin hydrochloride

Intervention Type: DRUG

100 mg/m² every 3 weeks

fluorouracil

Intervention Type: DRUG

500 mg/m² every 3 weeks

ixabepilone

Intervention Type: DRUG

40 mg/m² every 3 weeks

Interventions

cyclophosphamide

500 mg/m² every 3 weeks

Intervention Type: DRUG

Docetaxel

100 mg/m² every 3 weeks

Intervention Type: DRUG

epirubicin hydrochloride

100 mg/m² every 3 weeks

Intervention Type: DRUG

fluorouracil

500 mg/m² every 3 weeks

Intervention Type: DRUG

ixabepilone

40 mg/m² every 3 weeks

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Histologically proven invasive unilateral breast cancer (regardless of the type)

• Initial clinical condition compatible with complete initial resection
• No residual macro or microscopic tumor after surgical excision
• Node-positive disease (i.e., positive sentinel node or positive axillary clearance) (N+) or node-negative disease (-) meeting the following criteria :

• Stage II or III disease
• pT >20 mm (T1-4)
• Patients must meet 1 of the following hormone-receptor criteria:

• Node-positive patients: triple-negative* tumor (HER2 negative, estrogen-receptor [ER] negative, and progesterone receptor [PR] negative) OR double-negative (HER2 negative, PR negative, and ER+)
• Node-negative patients: triple-negative* tumor only
• NOTE: *Hormone-receptor negativity is defined as ER <10% and PR <10% by IHC and HER2 negativity is defined as IHC 0-1+ OR IHC 2+ and FISH or CISH negative
• Must be able to begin chemotherapy no later than day 49 after the initial surgery

• Female
• Pre- or postmenopausal
• ECOG performance status 0-1
• Peripheral neuropathy ≤grade 1
• Neutrophil count ≥2,000/mm³
• Platelet count ≥100,000/mm³
• Hemoglobin >9 g/dL
• AST and ALT ≤1.5 times upper limit of normal (ULN)
• Alkaline phosphatase ≤2.5 times ULN
• Total bilirubin ≤1.0 times ULN
• Serum creatinine ≤1.5 times ULN
• LVEF ≥50% by MUGA scan or echocardiography
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for up to 8 weeks after completion of study treatment

Exclusion Criteria

• Clinically or radiologically detectable metastases (M0)
• Bilateral breast cancer or contralateral ductal carcinoma in situ
• Any metastatic impairment, including homolateral subclavicular node involvement, regardless of its type
• Any tumor ≥T4a (cutaneous invasion, deep adherence, inflammatory breast cancer)
• HER 2 overexpression defined as IHC 3+ OR IHC 2+ and FISH or CISH positive
• Any clinically or radiologically suspect and non-explored damage to the contralateral breast

PATIENT CHARACTERISTICS:

• Previous cancer (except cutaneous baso-cellular epithelioma or uterine peripheral epithelioma) in the preceding 5 years, including invasive contralateral breast cancer
• Patients with any other concurrent severe and/or uncontrolled medical disease or infection that could compromise participation in the study
• Clinically significant cardiovascular disease within the past 6 months including any of the following:

• Unstable angina
• Congestive heart failure
• Uncontrolled hypertension (i.e., blood pressure >150/90 mm Hg)
• Myocardial infarction
• Cerebral vascular accidents
• Known prior severe hypersensitivity reactions to agents containing Cremophor EL
• Patients with any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
• Patients deprived of liberty or placed under the authority of a tutor

PRIOR CONCURRENT THERAPY:

• At least 2 weeks since prior minor surgery (excluding breast biopsy) and adequately recovered
• At least 3 weeks since prior major surgery and adequately recovered
• No prior chemotherapy, hormonal therapy, or radiotherapy
• More than 72 hours since prior and no concurrent treatment with any of the following strong inhibitors of CYP3A4:

• Amiodarone
• Clarithromycin
• Amprenavir
• Delavirdine
• Voriconazole
• Erythromycin
• Fluconazole
• Itraconazole
• Ketoconazole
• Indinavir
• Nelfinavir
• Ritonavir
• Saquinavir
• No concurrent participation in another therapeutic trial involving an experimental drug

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

Sponsors

UNICANCER

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mario Campone, MD

Role: PRINCIPAL_INVESTIGATOR

ICO Centre Regional Rene Gauducheau

Locations

Mayo Clinic Scottsdale

Scottsdale, Arizona, United States

CCOP - Colorado Cancer Research Program

Denver, Colorado, United States

Mayo Clinic - Jacksonville

Jacksonville, Florida, United States

CCOP - Northern Indiana CR Consortium

South Bend, Indiana, United States

CCOP - Cedar Rapids Oncology Project

Cedar Rapids, Iowa, United States

Siouxland Hematology-Oncology Associates, LLP

Sioux City, Iowa, United States

Cancer Center of Kansas, PA - Wichita

Wichita, Kansas, United States

Duluth Clinic Cancer Center - Duluth

Duluth, Minnesota, United States

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

CCOP - Metro-Minnesota

Saint Louis Park, Minnesota, United States

Southeast Nebraska Hematology Oncology Consultants at Southeast Nebraska Cancer Center

Lincoln, Nebraska, United States

CCOP - Missouri Valley Cancer Consortium

Omaha, Nebraska, United States

Roger Maris Cancer Center at MeritCare Hospital

Fargo, North Dakota, United States

CCOP - Dayton

Dayton, Ohio, United States

CCOP - Geisinger Clinic and Medical Center

Danville, Pennsylvania, United States

Oncology Associates at Rapid City Regional Hospital

Rapid City, South Dakota, United States

Green Bay Oncology, Limited at St. Mary's Hospital

Green Bay, Wisconsin, United States

Institut Jules Bordet

Brussels, , Belgium

Centre de Sante des Fagnes

Chimay, , Belgium

Centre Hospitalier Hutois

Huy, , Belgium

Cazk Groeninghe - Campus Maria's Voorzienigheid

Kortrijk, , Belgium

CHR - Clinique Saint Joseph - Hopital de Warqueguies

Mons, , Belgium

Clinique Saint-Pierre

Ottignies, , Belgium

Clinique Universitaire De Mont-Godinne

Yvoir, , Belgium

Clinique Claude Bernard

Albi, , France

Centre Paul Papin

Angers, , France

Centre Hospitalier d'Annecy

Annecy, , France

Centre Hospitalier d'Auxerre

Auxerre, , France

Institut Sainte Catherine

Avignon, , France

Centre Hospitalier de Blois

Blois, , France

Institut Bergonie

Bordeaux, , France

Clinique Tivoli

Bordeaux, , France

Centre Hospitalier Docteur Duchenne

Boulogne-sur-Mer, , France

Centre Hospitalier de Fleyriat

Bourg-en-Bresse, , France

CHU Hopital A. Morvan

Brest, , France

Centre Regional Francois Baclesse

Caen, , France

Centre Hospitalier Regional de Chambery

Chambéry, , France

Centre Hospitalier de Chateaubriant

Châteaubriant, , France

Centre Jean Perrin

Clermont-Ferrand, , France

Clinique des Cedres

Cornebarrieu, , France

Hopital Intercommunal De Creteil

Créteil, , France

Centre Hospitalier de Dax

Dax, , France

Centre de Lutte Contre le Cancer Georges-Francois Leclerc

Dijon, , France

Clinique Claude Bernard

Ermont, , France

Hopital Jean Monnet

Épinal, , France

Hopital Andre Mignot

Le Chesnay, , France

CMC Les Ormeaux

Le Havre, , France

Polyclinique des Quatre Pavillons

Lormont, , France

Centre Leon Berard

Lyon, , France

Centre de Radiotherapie et Oncologie Saint-Faron

Mareuil-lès-Meaux, , France

Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes

Marseille, , France

Hopital Notre-Dame de Bon Secours

Metz, , France

Hopital Clinique Claude Bernard

Metz, , France

Centre Hospitalier General de Mont de Marsan

Mont-de-Marsan, , France

Clinique du Pont de Chaume

Montauban, , France

Centre Hospitalier Intercommunal Le Raincy - Montfermeil

Montfermeil, , France

Centre Hospitalier de Montlucon

Montluçon, , France

Centre Hospitalier

Mulhouse, , France

Clinique D'Occitanie

Muret, , France

Clinique Hartmann

Neuilly-sur-Seine, , France

Centre Antoine Lacassagne

Nice, , France

Clinique De Valdegour

Nîmes, , France

Hopital Saint Michel

Paris, , France

Institut Curie Hopital

Paris, , France

Centre Hospitalier - Pau

Pau, , France

Centre Hospitalier de Perpignan

Perpignan, , France

Polyclinique Francheville

Périgueux, , France

Institut Jean Godinot

Reims, , France

Polyclinique De Courlancy

Reims, , France

Centre Eugene Marquis

Rennes, , France

Centre Hospitalier de Rodez

Rodez, , France

Clinique Armoricaine De Radiologie

Saint-Brieuc, , France

Centre Rene Huguenin

Saint-Cloud, , France

Centre Regional Rene Gauducheau

Saint-Herblain, , France

Clinique de l'Union

Saint-Jean, , France

Institut de Cancerologie de la Loire

Saint-Priest-en-Jarez, , France

Clinique de l'Orangerie

Strasbourg, , France

Centre Paul Strauss

Strasbourg, , France

Polyclinique de L'Ormeau

Tarbes, , France

Centre Hospitalier Regional Metz Thionville

Thionville, , France

Institut Claudius Regaud

Toulouse, , France

Clinique Du Parc

Toulouse, , France

Centre Hospitalier Universitaire Bretonneau de Tours

Tours, , France

Centre Alexis Vautrin

Vandœuvre-lès-Nancy, , France

Centre d'Oncologie Saint-Yves

Vannes, , France

Institut Gustave Roussy

Villejuif, , France

Countries

United States; Belgium; France

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://www.ncbi.nlm.nih.gov/pubmed/30267987

Abstract primary endpoint results

Other Identifiers

PACS-08/0610

Identifier Type: OTHER

Identifier Source: secondary_id

2006-006494-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

PACS08-Tavlx

Identifier Type: OTHER

Identifier Source: secondary_id

BMS-UNICANCER-PACS-08/0610

Identifier Type: OTHER

Identifier Source: secondary_id

AMGEN-UNICANCER-PACS-08/0610

Identifier Type: OTHER

Identifier Source: secondary_id

PACS08 - UC-0140/0610

Identifier Type: -

Identifier Source: org_study_id