Clinical trial NCT00053911: Combination Chemotherapy Compared With Observation After Surgery in Treating Women With Relapsed Nonmetastatic Breast Cancer
Official title: Randomized And Multicentric Phase III Study Evaluating The Benefit By Using A Chemotherapy With FEC 100 And Docetaxel In Non Metastatic Breast Cancer Which Has Relapsed After A Conservative Surgery
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Breast Cancer
Keywords: recurrent breast cancer
stage I breast cancer
stage II breast cancer
stage IIIA breast cancer
Lead sponsor: UNICANCER
Sponsor class: OTHER
First posted: 2003-02-06
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug, and giving them after surgery, may kill any remaining tumor cells following surgery. It is not yet known whether combination chemotherapy is more effective than observation in treating relapsed nonmetastatic breast cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy with that of observation in treating women who have undergone surgery for relapsed nonmetastatic breast cancer.

Detailed description: OBJECTIVES:

* Compare the efficacy of adjuvant cyclophosphamide, epirubicin, and fluorouracil vs observation, in terms of disease-free 5-year survival, in women who have undergone resection for relapsed nonmetastatic breast cancer after initial conservative surgery.
* Compare the overall survival of women treated with these regimens.
* Determine the tolerance of these women to the chemotherapy regimen.
* Correlate prognostic factors of survival with efficacy of the chemotherapy regimen in these women.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to menopausal status and participating center. Patients are randomized to 1 of 2 treatment arms. Study begins within 42 days after resection of recurrent disease.

* Arm I: Patients receive fluorouracil IV over 1 hour, epirubicin IV over 1 hour, and cyclophosphamide IV over 1 hour on day 1. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive docetaxel IV over 1 hour on day 1. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.
* Arm II: Patients are examined on days 1 and 63.

Patients who are hormone receptor positive also receive one of the following hormonal therapy regimens, depending on menopausal status:

* Oral tamoxifen daily for 5 years
* Oral tamoxifen daily for 5 years and oral luteinizing hormone-releasing hormone (LHRH) agonist therapy (e.g., goserelin) for 3 years
* Oral LHRH agonist therapy (e.g., goserelin) for 3 years
* Oral antiaromatase therapy (e.g., anastrozole) for 5 years Patients also undergo radiotherapy and may also undergo second complete resection.

Patients are followed every 6 months for 5 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 370 patients (185 per treatment arm) will be accrued for this study within 3 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed adenocarcinoma of the breast

  * No contralateral breast cancer
* Local tumor recurrence more than 6 months after conservative surgery
* Complete or conservative resection of the recurrent tumor NOTE: Initial complete surgical resection not allowed
* No local inflammatory disease or disease that is not amenable to complete surgical resection
* No positive axillary lymph nodes
* No distant metastases, including subclavicular lymph nodes
* Hormone receptor status:

  * Hormone receptor status known

PATIENT CHARACTERISTICS:

Age

* 18 to 65

Sex

* Female

Menopausal status

* Menopausal status known

Performance status

* ECOG 0-1

Life expectancy

* Not specified

Hematopoietic

* Neutrophil count at least 2,000/mm\^3
* Platelet count at least 100,000/mm\^3

Hepatic

* Bilirubin no greater than upper limit of normal (ULN)
* Transaminases no greater than 1.5 times ULN
* Alkaline phosphatase no greater than 2.5 times ULN
* No chronic hepatitis B
* No active hepatitis C

Renal

* Not specified

Cardiovascular

* Cardiac function normal by echocardiogram or isotopes

Other

* No contraindications to anthracyclines such as any of the following:

  * Prior doxorubicin over 300 mg/m\^2
  * Prior epirubicin over 600 mg/m\^2
  * Prior mitoxantrone over 90 mg/m\^2
* No other invasive malignancy
* No chronic somatic or psychiatric condition that would preclude study participation
* No familial, social, geographic, or psychological reason that would preclude study participation
* Not pregnant
* Fertile patients must use effective contraception
* HIV negative
* CA 153 no greater than 2 times ULN

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Not specified

Chemotherapy

* See Patient Characteristics-Other
* No prior neoadjuvant chemotherapy

Endocrine therapy

* No prior neoadjuvant hormonal therapy

Radiotherapy

* No prior neoadjuvant radiotherapy

Surgery

* See Disease Characteristics
* At least 41 days since prior surgery

Primary outcomes:
measure: Evaluation of the disease free survival
timeFrame: 5 years
Secondary outcomes:
measure: Evaluation of the overall survival
timeFrame: 5 years
Other outcomes:
Locations:
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: Avignon
country: France
facility: Institut Sainte Catherine
city: Bordeaux
country: France
facility: Institut Bergonie
city: Bourg En Bresse
country: France
facility: C.H. Bourg En Bresse
city: Brest
country: France
facility: CHU Hopital A. Morvan
city: Brive
country: France
facility: Centre Hospitalier General
city: Caen
country: France
facility: Centre Regional Francois Baclesse
city: Clermont-Ferrand
country: France
facility: Centre Jean Perrin
city: Compiegne
country: France
facility: Centre Hospitalier Compiegne
city: Harfleur
country: France
facility: Clinique du Petit Colmouilins
city: Lille
country: France
facility: Centre Oscar Lambret
city: Marseille
country: France
facility: Institut J. Paoli and I. Calmettes
city: Metz
country: France
facility: Hopital Notre-Dame de Bon Secours
city: Montbeliard
country: France
facility: C.H. General Andre Boulloche
city: Montpellier
country: France
facility: Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
city: Mulhouse
country: France
facility: Centre Hospitalier de Mulhouse
city: Nantes-Saint Herblain
country: France
facility: Centre Regional Rene Gauducheau
city: Perpignan
country: France
facility: Clinique Saint - Pierre
city: Rennes
country: France
facility: Centre Eugene Marquis
city: Saint Brieux
country: France
facility: Clinique Armoricaine De Radiologie
city: Tarbes
country: France
facility: Polyclinique de L'Ormeau
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Toulouse
country: France
facility: Hopital J. Ducuing
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: Institut du Cancer de Montpellier - Val d'Aurelle
name: Gilles Romieu, MD
role: STUDY_CHAIR
References: