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

Breast Cancer Clinical Trial

— TavIx  

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00630032
• Other study ID #: PACS08 - UC-0140/0610
• Secondary ID: PACS-08/06102006
• Status: Completed
• Phase: Phase 3
• Start date: September 2007
• Est. completion date: September 3, 2020

Study information

• Verified date: February 2024
• Source: UNICANCER
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 762
• Est. completion date: September 3, 2020
• Est. primary completion date: June 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• cyclophosphamide
500 mg/m² every 3 weeks
• Docetaxel
100 mg/m² every 3 weeks
• epirubicin hydrochloride
100 mg/m² every 3 weeks
• fluorouracil
500 mg/m² every 3 weeks
• ixabepilone
40 mg/m² every 3 weeks

Locations

Country	Name	City	State
Belgium	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
France	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	Clinique Tivoli	Bordeaux
France	Institut Bergonie	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	Chambery
France	Centre Hospitalier de Chateaubriant	Chateaubriant cedex
France	Centre Jean Perrin	Clermont-Ferrand
France	Clinique des Cedres	Cornebarrieu
France	Hopital Intercommunal De Creteil	Creteil
France	Centre Hospitalier de Dax	Dax
France	Centre de Lutte Contre le Cancer Georges-Francois Leclerc	Dijon
France	Hopital Jean Monnet	Epinal
France	Clinique Claude Bernard	Ermont
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 Les Meaux
France	Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes	Marseille
France	Hopital Clinique Claude Bernard	Metz
France	Hopital Notre-Dame de Bon Secours	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	Montlucon
France	Centre Hospitalier	Mulhouse
France	Clinique D'Occitanie	Muret
France	Clinique Hartmann	Neuilly sur Seine
France	Centre Antoine Lacassagne	Nice
France	Clinique De Valdegour	Nimes
France	Hopital Saint Michel	Paris
France	Institut Curie Hopital	Paris
France	Centre Hospitalier - Pau	Pau
France	Polyclinique Francheville	Perigueux
France	Centre Hospitalier de Perpignan	Perpignan
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	Clinique de l'Union	Saint Jean
France	Institut de Cancerologie de la Loire	Saint Priest en Jarez
France	Centre Regional Rene Gauducheau	Saint-Herblain
France	Centre Paul Strauss	Strasbourg
France	Clinique de l'Orangerie	Strasbourg
France	Polyclinique de L'Ormeau	Tarbes
France	Centre Hospitalier Regional Metz Thionville	Thionville
France	Clinique Du Parc	Toulouse
France	Institut Claudius Regaud	Toulouse
France	Centre Hospitalier Universitaire Bretonneau de Tours	Tours
France	Centre Alexis Vautrin	Vandoeuvre-les-Nancy
France	Centre d'Oncologie Saint-Yves	Vannes
France	Institut Gustave Roussy	Villejuif
United States	CCOP - Cedar Rapids Oncology Project	Cedar Rapids	Iowa
United States	CCOP - Geisinger Clinic and Medical Center	Danville	Pennsylvania
United States	CCOP - Dayton	Dayton	Ohio
United States	CCOP - Colorado Cancer Research Program	Denver	Colorado
United States	Duluth Clinic Cancer Center - Duluth	Duluth	Minnesota
United States	Roger Maris Cancer Center at MeritCare Hospital	Fargo	North Dakota
United States	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin
United States	Mayo Clinic - Jacksonville	Jacksonville	Florida
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	Oncology Associates at Rapid City Regional Hospital	Rapid City	South Dakota
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	Mayo Clinic Scottsdale	Scottsdale	Arizona
United States	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa
United States	CCOP - Northern Indiana CR Consortium	South Bend	Indiana
United States	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
UNICANCER

Countries where clinical trial is conducted

United States,  Belgium,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Overall Survival	The overall survival is the length of time from randomization that patients enrolled in the study are still alive.	At 5 years

External Links

•   Abstract primary endpoint results