RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs to kill more tumor cells. It is not yet known if high dose chemotherapy plus peripheral stem cell transplantation is more effective than standard therapy for breast cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of high dose chemotherapy plus peripheral stem cell transplantation with that of standard therapy in treating women who have locally recurrent or metastatic breast cancer.

Condition	Treatment or Intervention	Phase
stage IV breast cancer recurrent breast cancer Quality of Life	Drug: cyclophosphamide  Drug: epirubicin  Drug: filgrastim  Drug: fluorouracil  Drug: thiotepa	Phase III

Further Study Details: 

OBJECTIVES: I. Evaluate the effect on 3-year survival of intensive chemotherapy with cyclophosphamide/thiotepa with peripheral blood stem cell rescue in patients with locally recurrent or metastatic breast cancer who respond to induction therapy with epirubicin/fluorouracil/cyclophosphamide. II. Evaluate the effects of this intensive treatment on patient quality of life. III. Evaluate tumor response and progression-free survival after intensification.

PROTOCOL OUTLINE: This is a randomized study. Patients are stratified by clinical/therapeutic hormone sensitivity and participating institution. All patients receive induction therapy with epirubicin, fluorouracil, and cyclophosphamide (FEC 100) every 3 weeks for up to 4 courses, with response evaluated after at least 2 courses. Patients with a complete response or at least a 50% partial response are randomized either to no further therapy or to receive intensification chemotherapy. Patients randomized to intensification undergo peripheral blood stem cell (PBSC) harvest with G-CSF mobilization after the third or fourth induction course. Three to 6 weeks after induction, patients receive intensification chemotherapy with cyclophosphamide/thiotepa followed by PBSC. Post-transplant G-CSF is given for hematopoietic support. No concurrent hormonal therapy is permitted during induction; local irradiation of multifocal tumors is allowed provided response is still evaluable. Local therapy (excision of single metastasis, radiotherapy to metastatic site) is permitted after completion of protocol therapy. Treatment of relapsed disease is at the discretion of the investigator. Patients are followed every 3 months for 3 years or until relapse, then every 6 months.

PROJECTED ACCRUAL: A total of 180 patients will be accrued over 3 years in this multicenter study.

Ages Eligible for Study:  up to  59 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically or cytologically proven glandular breast cancer
• Metastatic or locoregionally relapsed disease for which curative surgery and/or radiotherapy is not feasible; Histologic/cytologic confirmation of metastasis as feasible
• Progression required within the month prior to entry, whether or not it occurs on hormonal therapy
• No clinically detectable cerebral or meningeal involvement
• Measurable lesion required, including soft tissue site, lymphadenopathy, or visceral site The following are not considered measurable: Bony sites of involvement; Ascites; Pulmonary lymphangitic carcinomatosis; Skin lesions; Pathologic CEA or CA 15.3 levels; Laboratory changes; Pleural effusion
• Hormone receptor status: Not specified

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: No prior palliative chemotherapy; At least 1 year since adjuvant chemotherapy; Maximum prior cumulative anthracycline doses as follows: Epirubicin no greater than 450 mg per square meter; Doxorubicin no greater than 300 mg per square meter; Pirarubicin no greater than 300 mg per square meter; Mitoxantrone no greater than 60 mg per square meter
• Endocrine therapy: Prior hormonal therapy allowed; See Disease Characteristics
• Radiotherapy: At least 6 weeks since radiotherapy to more than one third of hematopoietic regions
• Surgery: Not specified

--Patient Characteristics--

• Age: Under 60
• Sex: Women only
• Menopausal status: Not specified
• Performance status: WHO 0-2
• Life expectancy: Greater than 3 months
• Hematopoietic: ANC at least 2,000; Platelets at least 100,000
• Hepatic: Bilirubin no greater than 2.0 mg/dL (35 micromoles/L)
• Renal: Creatinine no greater than 1.3 mg/dL (130 micromoles/L)
• Cardiovascular: No congestive heart failure, even if stable; No coronary artery disease No myocardial infarction within 6 months; Ventricular ejection fraction (resting) normal by isotopic scan or echocardiogram; No evidence of cardiac disease on EKG
• Other: No active infection; No second malignancy except: In situ cervical carcinoma; Basal cell skin carcinoma; No pregnant women; No psychological, familial, social, or geographical contraindication to regular follow-up

France
      C.H. Bourg En Bresse, Bourg-en-Bresse,  01012,  France
      C.H.U. de Brest, Brest,  29200,  France
      C.H.U. Saint Etienne Hospital Nord, Saint-Etienne,  42055,  France
      Centre Alexis Vautrin, Vandoeuvre-les-Nancy,  54511,  France
      Centre Antoine Lacassagne, Nice,  06189,  France
      Centre de Lute Contre le Cancer,Georges-Francois Leclerc, Dijon,  21079,  France
      Centre Eugene Marquis, Rennes,  35062,  France
      Centre Hospitalier General, Brive,  France
      Centre Hospitalier Universitaire Bretonneau de Tours, Tours,  37044,  France
      Centre Jean Perrin, Clermont-Ferrand,  63011,  France
      Centre Leon Berard, Lyon,  69373,  France
      Centre Oscar Lambret, Lille,  59020,  France
      Centre Paul Papin, Angers,  49036,  France
      Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle, Montpellier,  34298,  France
      Centre Regional Francois Baclesse, Caen,  14076,  France
      CHR de Besancon - Hopital Jean Minjoz, Besancon,  25030,  France
      CHRU de Nancy - Hopitaux de Brabois, Vandoeuvre-les-Nancy,  54511,  France
      Clinique Saint Vincent, Besancon,  25044,  France
      Federation Nationale des Centres de Lutte Contre le Cancer, Paris,  75654,  France
      Hopital Haut Leveque, Pessac,  33604,  France
      Hopital Jean Bernard, Poitiers,  86021,  France
      Hopital Louis Pasteur, Colmar,  68024,  France
      Hopital Notre-Dame de Bon Secours, Metz,  55038,  France
      Hopital Saint-Louis, Paris,  75475,  France
      Hopital Sainte Blandine, Metz,  57045,  France
      Hopital Tenon, Paris,  75970,  France
      Hopitaux Universitaire de Strasbourg, Strasbourg,  67091,  France
      Institut Bergonie, Bordeaux,  33076,  France
      Institut Claudius Regaud, Toulouse,  31052,  France
      Institut J. Paoli and I. Calmettes, Marseille,  13273,  France
      Institut Jean Godinot, Reims,  51056,  France
      Institut Prive de Cancerologie, Grenoble,  38100,  France

Study chairs or principal investigators

Pierre Biron,  Study Chair,  Federation Nationale des Centres de Lutte Contre le Cancer   

Study ID Numbers:  CDR0000065151; FRE-FNCLCC-PEGASE03; EU-96032
Record last reviewed:  May 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002870
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08