Clinical trial NCT00003730: Vinorelbine Plus Fluorouracil in Treating Women With Metastatic Breast Cancer
Official title: A Multicenter Randomized Trial, With Direct Individual Benefit, to Determine the Optimal Circadian Time of Vinorelbine Administration Combined With Chronomodulated Infusion of 5-Fluorouracil in Previously Treated Patients With Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Breast Cancer
Keywords: stage IV breast cancer
recurrent breast cancer
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
First posted: 2003-01-27
Enrollment: 80
Sex: FEMALE
Standard ages: CHILD
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 may kill more tumor cells.

PURPOSE: Randomized clinical trial to study the effectiveness of vinorelbine plus fluorouracil in treating women who have metastatic breast cancer that has been previously treated with at least one regimen of chemotherapy.

Detailed description: OBJECTIVES:

* Determine the least toxic time of vinorelbine administration when combined with chronomodulated fluorouracil in women with previously treated metastatic breast cancer.
* Determine the toxic effects and dose intensities of each drug in these women.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to prior chemotherapy (second line vs third line) and participating center. Patients are randomized to 1 of 8 vinorelbine dosing times (0000, 0300, 0600, 0900, 1200, 1500, 1800, or 2100).

Patients receive vinorelbine IV over 20 minutes on days 1 and 6 and fluorouracil IV over 12 hours according to a chronomodulated delivery rate (2200 to 1000 with a maximum dose at 0400) on days 1-4. Treatment repeats every 3 weeks for at least 3 courses in the absence of unacceptable toxicity.

Patients are followed for 30 days.

PROJECTED ACCRUAL: A minimum of 80 patients (10 per dosing time) will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed metastatic breast cancer
* At least 1 line of prior chemotherapy for metastatic disease (adjuvant or neoadjuvant chemotherapy is considered first line if completed less than one year prior to palliative chemotherapy)
* No cerebral metastases
* Hormonal receptor status:

  * Not specified

PATIENT CHARACTERISTICS:

Age:

* Not specified

Sex:

* Female

Menopausal status:

* Not specified

Performance status:

* WHO 0-2

Life expectancy:

* Not specified

Hematopoietic:

* Absolute neutrophil count at least 1,500/mm\^3
* Platelet count at least 100,000/mm \^3

Hepatic:

* Bilirubin no greater than 2.5 times upper limit of normal (ULN)
* AST/ALT no greater than 2.5 times ULN

Renal:

* Creatinine no greater than 1.58 mg/dL

Cardiovascular:

* No clinically significant cardiac insufficiency or ischemic disease

Pulmonary:

* No bronchoconstriction other than pulmonary lymphangitis

Other:

* No serious chronic disease
* No bowel obstruction
* Not pregnant or nursing

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* No concurrent immunotherapy
* No concurrent prophylactic growth factor

Chemotherapy:

* See Disease Characteristics
* At least 4 weeks since prior chemotherapy
* No prior high-dose chemotherapy
* No other concurrent chemotherapy

Endocrine therapy:

* No concurrent hormonal therapy
* No concurrent steroid therapy except in an emergency

Radiotherapy:

* At least 4 weeks since prior radiotherapy (for primary tumor or axillary or mammary chain treatment only)
* No concurrent radiotherapy

Surgery:

* Not specified

Other:

* No other concurrent antitumor therapy

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Antwerpen
country: Belgium
facility: VZW Monica Campus Eeuwfeestkliniek
city: Liege
country: Belgium
facility: C.H.C - Asbl
city: Liege
country: Belgium
facility: CHU Liege - Domaine Universitaire du Sart Tilman
city: Clermont-Ferrand
country: France
facility: Centre Jean Perrin
city: Dijon
country: France
facility: Centre de Lutte Contre le Cancer Georges-Francois Leclerc
city: Levallois-Perret
country: France
facility: Hopital Perpetuel Secours
city: Limoges
country: France
facility: Centre Hospital Regional Universitaire de Limoges
city: Paris
country: France
facility: Hopital Saint-Louis
city: Saint Cloud
country: France
facility: Centre Rene Huguenin
city: Saint Etienne
country: France
facility: Hopital Bellevue
city: Villejuif
country: France
facility: Hopital Paul Brousse
city: Iraklion (Heraklion)
country: Greece
facility: University Hospital of Heraklion
state: Crete
city: Candiolo (Turin)
country: Italy
facility: Istituto per la Ricerca e Cura del Cancro
city: Milano (Milan)
country: Italy
facility: Ospedale San Carlo Borromeo
city: Orbassano, (Torino)
country: Italy
facility: Azienda Ospedale S. Luigi - Universita Di Turin
city: Pavia
country: Italy
facility: Fondazione Salvatore Maugeri
city: Rome
country: Italy
facility: Istituti Fisioterapici Ospitalieri - Roma
Study officials:
affiliation: Centre Georges Francois Leclerc
name: Bruno Coudert, MD
role: STUDY_CHAIR
References:
citation: Coudert B, Focan C, Genet D, Giacchetti S, Cvickovic F, Zambelli A, Fillet G, Chollet P, Amoroso D, Van Der Auwera J, Lentz MA, Marreaud S, Baron B, Gorlia T, Biville F, Levi F. A randomized multicenter study of optimal circadian time of vinorelbine combined with chronomodulated 5-fluorouracil in pretreated metastatic breast cancer patients: EORTC trial 05971. Chronobiol Int. 2008 Sep;25(5):680-96. doi: 10.1080/07420520802384036.