Clinical trial NCT00630032: Safety and Efficacy Comparison of Docetaxel and Ixabepilone in Non Metastatic Poor Prognosis Breast Cancer
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Keywords: stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
Lead sponsor: UNICANCER
Sponsor class: OTHER
First posted: 2008-03-06
Enrollment: 762
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants With Disease-free Survival (DFS)
timeFrame: At 5 years
Secondary outcomes:
measure: Number of Disease-free Survival Events for Triple-negative Subgroup
timeFrame: At 5 years
measure: Number of Disease-free Survival Events for ER+/PR-/HER2- Subgroup
timeFrame: At 5 years
measure: Number of Distant Metastasis-free Survival Events for the Whole Population
timeFrame: At 5 years
measure: Number of Event-free Survival
timeFrame: At 5 years
measure: Overall Survival
timeFrame: At 5 years
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic Scottsdale
state: Arizona
city: Denver
country: United States
facility: CCOP - Colorado Cancer Research Program
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic - Jacksonville
state: Florida
city: South Bend
country: United States
facility: CCOP - Northern Indiana CR Consortium
state: Indiana
city: Cedar Rapids
country: United States
facility: CCOP - Cedar Rapids Oncology Project
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Hematology-Oncology Associates, LLP
state: Iowa
city: Wichita
country: United States
facility: Cancer Center of Kansas, PA - Wichita
state: Kansas
city: Duluth
country: United States
facility: Duluth Clinic Cancer Center - Duluth
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Saint Louis Park
country: United States
facility: CCOP - Metro-Minnesota
state: Minnesota
city: Lincoln
country: United States
facility: Southeast Nebraska Hematology Oncology Consultants at Southeast Nebraska Cancer Center
state: Nebraska
city: Omaha
country: United States
facility: CCOP - Missouri Valley Cancer Consortium
state: Nebraska
city: Fargo
country: United States
facility: Roger Maris Cancer Center at MeritCare Hospital
state: North Dakota
city: Dayton
country: United States
facility: CCOP - Dayton
state: Ohio
city: Danville
country: United States
facility: CCOP - Geisinger Clinic and Medical Center
state: Pennsylvania
city: Rapid City
country: United States
facility: Oncology Associates at Rapid City Regional Hospital
state: South Dakota
city: Green Bay
country: United States
facility: Green Bay Oncology, Limited at St. Mary's Hospital
state: Wisconsin
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Chimay
country: Belgium
facility: Centre de Sante des Fagnes
city: Huy
country: Belgium
facility: Centre Hospitalier Hutois
city: Kortrijk
country: Belgium
facility: Cazk Groeninghe - Campus Maria's Voorzienigheid
city: Mons
country: Belgium
facility: CHR - Clinique Saint Joseph - Hopital de Warqueguies
city: Ottignies
country: Belgium
facility: Clinique Saint-Pierre
city: Yvoir
country: Belgium
facility: Clinique Universitaire De Mont-Godinne
city: Albi
country: France
facility: Clinique Claude Bernard
city: Angers
country: France
facility: Centre Paul Papin
city: Annecy
country: France
facility: Centre Hospitalier d'Annecy
city: Auxerre
country: France
facility: Centre Hospitalier d'Auxerre
city: Avignon
country: France
facility: Institut Sainte Catherine
city: Blois
country: France
facility: Centre Hospitalier de Blois
city: Bordeaux
country: France
facility: Institut Bergonie
city: Bordeaux
country: France
facility: Clinique Tivoli
city: Boulogne Sur Mer
country: France
facility: Centre Hospitalier Docteur Duchenne
city: Bourg-En-Bresse
country: France
facility: Centre Hospitalier de Fleyriat
city: Brest
country: France
facility: CHU Hopital A. Morvan
city: Caen
country: France
facility: Centre Regional Francois Baclesse
city: Chambery
country: France
facility: Centre Hospitalier Regional de Chambery
city: Chateaubriant cedex
country: France
facility: Centre Hospitalier de Chateaubriant
city: Clermont-Ferrand
country: France
facility: Centre Jean Perrin
city: Cornebarrieu
country: France
facility: Clinique des Cedres
city: Creteil
country: France
facility: Hopital Intercommunal De Creteil
city: Dax
country: France
facility: Centre Hospitalier de Dax
city: Dijon
country: France
facility: Centre de Lutte Contre le Cancer Georges-Francois Leclerc
city: Epinal
country: France
facility: Hopital Jean Monnet
city: Ermont
country: France
facility: Clinique Claude Bernard
city: Le Chesnay
country: France
facility: Hopital Andre Mignot
city: Le Havre
country: France
facility: CMC Les Ormeaux
city: Lormont
country: France
facility: Polyclinique des Quatre Pavillons
city: Lyon
country: France
facility: Centre Leon Berard
city: Mareuil Les Meaux
country: France
facility: Centre de Radiotherapie et Oncologie Saint-Faron
city: Marseille
country: France
facility: Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes
city: Metz
country: France
facility: Hopital Notre-Dame de Bon Secours
city: Metz
country: France
facility: Hopital Clinique Claude Bernard
city: Mont-de-Marsan
country: France
facility: Centre Hospitalier General de Mont de Marsan
city: Montauban
country: France
facility: Clinique du Pont de Chaume
city: Montfermeil
country: France
facility: Centre Hospitalier Intercommunal Le Raincy - Montfermeil
city: Montlucon
country: France
facility: Centre Hospitalier de Montlucon
city: Mulhouse
country: France
facility: Centre Hospitalier
city: Muret
country: France
facility: Clinique D'Occitanie
city: Neuilly sur Seine
country: France
facility: Clinique Hartmann
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Nimes
country: France
facility: Clinique De Valdegour
city: Paris
country: France
facility: Hopital Saint Michel
city: Paris
country: France
facility: Institut Curie Hopital
city: Pau
country: France
facility: Centre Hospitalier - Pau
city: Perigueux
country: France
facility: Polyclinique Francheville
city: Perpignan
country: France
facility: Centre Hospitalier de Perpignan
city: Reims
country: France
facility: Institut Jean Godinot
city: Reims
country: France
facility: Polyclinique De Courlancy
city: Rennes
country: France
facility: Centre Eugene Marquis
city: Rodez
country: France
facility: Centre Hospitalier de Rodez
city: Saint Brieuc
country: France
facility: Clinique Armoricaine De Radiologie
city: Saint Cloud
country: France
facility: Centre Rene Huguenin
city: Saint Jean
country: France
facility: Clinique de l'Union
city: Saint Priest en Jarez
country: France
facility: Institut de Cancerologie de la Loire
city: Saint-Herblain
country: France
facility: Centre Regional Rene Gauducheau
city: Strasbourg
country: France
facility: Clinique de l'Orangerie
city: Strasbourg
country: France
facility: Centre Paul Strauss
city: Tarbes
country: France
facility: Polyclinique de L'Ormeau
city: Thionville
country: France
facility: Centre Hospitalier Regional Metz Thionville
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Toulouse
country: France
facility: Clinique Du Parc
city: Tours
country: France
facility: Centre Hospitalier Universitaire Bretonneau de Tours
city: Vandoeuvre-les-Nancy
country: France
facility: Centre Alexis Vautrin
city: Vannes
country: France
facility: Centre d'Oncologie Saint-Yves
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: ICO Centre Regional Rene Gauducheau
name: Mario Campone, MD
role: PRINCIPAL_INVESTIGATOR
References: