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

Randomized, Open Label, Multicentric Phase III Evaluating the Benefit of a Sequential Regimen Associating FEC 100 and Ixabepilone in Adjuvant Treatment of Non Metastatic, Poor Prognosis Breast Cancer Defined as Triple-negative Tumor [HER2 Negative - ER Negative - PR Negative] or [HER2 Negative and PR Negative] Tumor; in Node Positive or Node Negative Patients.

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: cyclophosphamide; Drug: Docetaxel; Drug: epirubicin hydrochloride; Drug: fluorouracil; Drug: ixabepilone

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.

• Study Type: Interventional
• Enrollment (Actual): 762
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1000
    • Institut Jules Bordet
  • Chimay, Belgium, B-6460
    • Centre de Sante des Fagnes
  • Huy, Belgium, 4500
    • Centre Hospitalier Hutois
  • Kortrijk, Belgium, B-8500
    • Cazk Groeninghe - Campus Maria's Voorzienigheid
  • Mons, Belgium, B-7000
    • CHR - Clinique Saint Joseph - Hopital de Warqueguies
  • Ottignies, Belgium, B-1340
    • Clinique Saint-Pierre
  • Yvoir, Belgium, 5530
    • Clinique Universitaire De Mont-Godinne
• France
  • Albi, France, 81000
    • Clinique Claude Bernard
  • Angers, France, 49036
    • Centre Paul Papin
  • Annecy, France, 74011 Cedex
    • Centre Hospitalier D'annecy
  • Auxerre, France, 89011
    • Centre Hospitalier d'Auxerre
  • Avignon, France, 84082
    • Institut Sainte Catherine
  • Blois, France, 41000
    • Centre Hospitalier de Blois
  • Bordeaux, France, 33076
    • Institut Bergonie
  • Bordeaux, France, F-33000
    • Clinique Tivoli
  • Boulogne Sur Mer, France, 62200
    • Centre Hospitalier Docteur Duchenne
  • Bourg-En-Bresse, France, 01012
    • Centre Hospitalier de Fleyriat
  • Brest, France, 29609
    • CHU Hopital A. Morvan
  • Caen, France, 14076
    • Centre Regional Francois Baclesse
  • Chambery, France, 73011
    • Centre Hospitalier Regional de Chambery
  • Chateaubriant cedex, France, 44110
    • Centre Hospitalier de Chateaubriant
  • Clermont-Ferrand, France, 63011
    • Centre Jean Perrin
  • Cornebarrieu, France, 31700
    • Clinique des Cèdres
  • Creteil, France, 94010
    • Hopital Intercommunal De Creteil
  • Dax, France, 40107
    • Centre Hospitalier de Dax
  • Dijon, France, 21079
    • Centre de Lutte Contre le Cancer Georges-Francois Leclerc
  • Epinal, France, 88021
    • Hopital Jean Monnet
  • Ermont, France, 95120
    • Clinique Claude Bernard
  • Le Chesnay, France, 78157
    • Hopital Andre Mignot
  • Le Havre, France, 76600
    • CMC Les Ormeaux
  • Lormont, France, 33310
    • Polyclinique des Quatre Pavillons
  • Lyon, France, 69373
    • Centre Leon Berard
  • Mareuil Les Meaux, France, 77100
    • Centre de Radiotherapie et Oncologie Saint-Faron
  • Marseille, France, 13273
    • Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes
  • Metz, France, 57038
    • Hopital Notre-Dame de Bon Secours
  • Metz, France, 57070
    • Hopital Clinique Claude Bernard
  • Mont-de-Marsan, France, 40000
    • Centre Hospitalier General de Mont de Marsan
  • Montauban, France, 82017
    • Clinique du Pont de Chaume
  • Montfermeil, France, 93370
    • Centre Hospitalier Intercommunal Le Raincy - Montfermeil
  • Montlucon, France, 03113
    • Centre Hospitalier de Montlucon
  • Mulhouse, France, 68070
    • Centre Hospitalier
  • Muret, France, 31600
    • Clinique D'Occitanie
  • Neuilly sur Seine, France, 92200
    • Clinique Hartmann
  • Nice, France, 06189
    • Centre Antoine Lacassagne
  • Nimes, France, 30907
    • Clinique De Valdegour
  • Paris, France, 75015
    • Hopital Saint Michel
  • Paris, France, 75248
    • Institut Curie Hopital
  • Pau, France, 64046
    • Centre Hospitalier - Pau
  • Perigueux, France, 24004
    • Polyclinique Francheville
  • Perpignan, France, 66000
    • Centre Hospitalier de Perpignan
  • Reims, France, F-51100
    • Polyclinique de Courlancy
  • Reims, France, 51056
    • Institut Jean Godinot
  • Rennes, France, 35042
    • Centre Eugène Marquis
  • Rodez, France, 12027
    • Centre Hospitalier de Rodez
  • Saint Brieuc, France, F-22015
    • Clinique Armoricaine de Radiologie
  • Saint Cloud, France, 92211
    • Centre René Huguenin
  • Saint Jean, France, 31240
    • Clinique de l'Union
  • Saint Priest en Jarez, France, 42270
    • Institut de Cancérologie de la Loire
  • Saint-Herblain, France, 44805
    • Centre Regional Rene Gauducheau
  • Strasbourg, France, 67065
    • Centre Paul Strauss
  • Strasbourg, France, 67000
    • Clinique de l'Orangerie
  • Tarbes, France, 65000
    • Polyclinique de l'Ormeau
  • Thionville, France, 57312
    • Centre Hospitalier Regional Metz Thionville
  • Toulouse, France, 31052
    • Institut Claudius Regaud
  • Toulouse, France, 31078
    • Clinique du parc
  • Tours, France, 37044
    • Centre Hospitalier Universitaire Bretonneau de Tours
  • Vandoeuvre-les-Nancy, France, 54511
    • Centre Alexis Vautrin
  • Vannes, France, 56001
    • Centre d'Oncologie Saint-Yves
  • Villejuif, France, F-94805
    • Institut Gustave Roussy
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259-5499
      • Mayo Clinic Scottsdale
  • Colorado
    • Denver, Colorado, United States, 80224
      • CCOP - Colorado Cancer Research Program
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic - Jacksonville
  • Indiana
    • South Bend, Indiana, United States, 46601
      • CCOP - Northern Indiana CR Consortium
  • Iowa
    • Cedar Rapids, Iowa, United States, 52403-1206
      • CCOP - Cedar Rapids Oncology Project
    • Sioux City, Iowa, United States, 51101-1733
      • Siouxland Hematology-Oncology Associates, LLP
  • Kansas
    • Wichita, Kansas, United States, 67214-3728
      • Cancer Center of Kansas, PA - Wichita
  • Minnesota
    • Duluth, Minnesota, United States, 55805-1983
      • Duluth Clinic Cancer Center - Duluth
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center
    • Saint Louis Park, Minnesota, United States, 55416
      • CCOP - Metro-Minnesota
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • Southeast Nebraska Hematology Oncology Consultants at Southeast Nebraska Cancer Center
    • Omaha, Nebraska, United States, 68106
      • CCOP - Missouri Valley Cancer Consortium
  • North Dakota
    • Fargo, North Dakota, United States, 58122
      • Roger Maris Cancer Center at MeritCare Hospital
  • Ohio
    • Dayton, Ohio, United States, 45429
      • CCOP - Dayton
  • Pennsylvania
    • Danville, Pennsylvania, United States, 17822-2001
      • CCOP - Geisinger Clinic and Medical Center
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Oncology Associates at Rapid City Regional Hospital
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54303
      • Green Bay Oncology, Limited at St. Mary's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

DISEASE CHARACTERISTICS:

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

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:

Inclusion criteria:

• 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:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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)	Drug: cyclophosphamide; 500 mg/m² every 3 weeks; Drug: Docetaxel; 100 mg/m² every 3 weeks; Drug: epirubicin hydrochloride; 100 mg/m² every 3 weeks; Drug: fluorouracil; 500 mg/m² every 3 weeks
Experimental: 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);	Drug: cyclophosphamide; 500 mg/m² every 3 weeks; Drug: epirubicin hydrochloride; 100 mg/m² every 3 weeks; Drug: fluorouracil; 500 mg/m² every 3 weeks; Drug: ixabepilone; 40 mg/m² every 3 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Disease-free Survival (DFS)	DFS is defined as the interval between the date of randomization and the date of breast cancer relapse (local, regional or distant) or the date of invasive contralateral breast cancer or death from any cause, whichever occurs first	At 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Disease-free Survival Events for Triple-negative Subgroup	DFS is defined as the interval between the date of randomization and the date of breast cancer relapse (local, regional or distant) or the date of invasive contralateral breast cancer or death from any cause, whichever occurs first in participants with triple negative breast cancer only.	At 5 years
Number of Disease-free Survival Events for ER+/PR-/HER2- Subgroup	DFS is defined as the interval between the date of randomization and the date of breast cancer relapse (local, regional or distant) or the date of invasive contralateral breast cancer or death from any cause, whichever occurs first in participants with ER+/PR-/HER2- breast cancer only.	At 5 years
Number of Distant Metastasis-free Survival Events for the Whole Population	The distant metastases-free survival is the length of time during and after the treatment for cancer that a patient is still alive and the cancer has not spread to other parts of the body.	At 5 years
Number of Event-free Survival	The Event-free Survival is defined as the interval between the date of randomization and the date of breast cancer relapse (local, regional or distant) or the date of invasive contralateral breast cancer or the date of second neoplasia, or the date of death from any cause, whichever occurs first.	At 5 years
Overall Survival	The overall survival is the length of time from randomization that patients enrolled in the study are still alive.	At 5 years

Collaborators and Investigators

• Sponsor: UNICANCER
• Investigators: Principal Investigator: Mario Campone, MD, ICO Centre Regional Rene Gauducheau

Publications and helpful links

Helpful Links

• Abstract primary endpoint results

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2007
• Primary Completion (Actual): June 1, 2017
• Study Completion (Actual): September 3, 2020

Study Registration Dates

• First Submitted: March 5, 2008
• First Submitted That Met QC Criteria: March 5, 2008
• First Posted (Estimated): March 6, 2008

Study Record Updates

• Last Update Posted (Estimated): February 21, 2024
• Last Update Submitted That Met QC Criteria: February 20, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: stage IIIA breast cancer; stage IIIB breast cancer; stage II breast cancer; stage IIIC breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Docetaxel; Cyclophosphamide; Fluorouracil; Epirubicin
• Other Study ID Numbers: PACS08 - UC-0140/0610; PACS-08/0610 (Other Identifier: UNICANCER); 2006-006494-24 (EudraCT Number); PACS08-Tavlx (Other Identifier: UNICANCER); BMS-UNICANCER-PACS-08/0610 (Other Identifier: UNICANCER); AMGEN-UNICANCER-PACS-08/0610 (Other Identifier: UNICANCER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Unicancer will share de-identified individual data that underlie the results reported. A decision concerning the sharing of other study documents, including protocol and statistical analysis plan will be examined upon request.
• IPD Sharing Time Frame: Unicancer will consider access to study data upon written detailed request sent to Unicancer, from 6 months until 5 years after publication of summary data.
• IPD Sharing Access Criteria: The data shared will be limit to that required for independent mandated verification of the published results, the applicant will need authorization from Unicancer for personal access, and data will only be transferred after signing of a data access agreement.