Clinical trial NCT00002870: High Dose Chemotherapy Plus Peripheral Stem Cell Transplantation Compared With Standard Therapy in Treating Women With Locally Recurrent or Metastatic Breast Cancer
Official title: A RANDOMIZED, MULTI-CENTRE PHASE III TRIAL TO EVALUATE THE ROLE OF INTENSIFIED THERAPY WITH AUTOLOGOUS TRANSPLANTATION OF HEMATOPOIETIC STEM CELLS IN ADVANCED OR METASTATIC BREAST CANCER RESPONDING TO INDUCTION CHEMOTHERAPY
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Keywords: stage IV breast cancer
recurrent breast cancer
Lead sponsor: UNICANCER
Sponsor class: OTHER
First posted: 2004-05-12
Enrollment: 180
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 59
Standard ages: 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 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.

Detailed description: OBJECTIVES: I. Evaluate the effect on 3-year survival of intensive chemotherapy with cyclophosphamide/thiotepa with peripheral blood stem cell rescue in women 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.

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.

Eligibility 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

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

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

Primary outcomes:
measure: Disease free survival
timeFrame: 5 years
Secondary outcomes:
Other outcomes:
Locations:
city: Angers
country: France
facility: Centre Paul Papin
city: Besancon
country: France
facility: CHR de Besancon - Hopital Jean Minjoz
city: Besancon
country: France
facility: Clinique Saint Vincent
city: Bordeaux
country: France
facility: Institut Bergonie
city: Bourg En Bresse
country: France
facility: C.H. Bourg En Bresse
city: Brest
country: France
facility: C.H.U. de Brest
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: Colmar
country: France
facility: Hopital Louis Pasteur
city: Dijon
country: France
facility: Centre de Lute Contre le Cancer,Georges-Francois Leclerc
city: Grenoble
country: France
facility: Institut Prive de Cancerologie
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lyon
country: France
facility: Centre Leon Berard
city: Marseille
country: France
facility: Institut J. Paoli and I. Calmettes
city: Metz
country: France
facility: Hopital Notre-Dame de Bon Secours
city: Metz
country: France
facility: Hopital Sainte Blandine
city: Montpellier
country: France
facility: Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Paris
country: France
facility: Hopital Saint-Louis
city: Paris
country: France
facility: Federation Nationale des Centres de Lutte Contre le Cancer
city: Paris
country: France
facility: Hopital Tenon
city: Pessac
country: France
facility: Hopital Haut Leveque
city: Poitiers
country: France
facility: Hopital Jean Bernard
city: Reims
country: France
facility: Institut Jean Godinot
city: Rennes
country: France
facility: Centre Eugene Marquis
city: Saint Etienne
country: France
facility: C.H.U. Saint Etienne Hospital Nord
city: Strasbourg
country: France
facility: Hopitaux Universitaire de Strasbourg
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Tours
country: France
facility: Centre Hospitalier Universitaire Bretonneau de Tours
city: Vandoeuvre-les-Nancy
country: France
facility: Centre Alexis Vautrin
city: Vandoeuvre-Les-Nancy
country: France
facility: CHRU de Nancy - Hopitaux de Brabois
Study officials:
affiliation: Centre Leon Berard
name: Pierre Biron, MD
role: STUDY_CHAIR
References:
citation: Biron P, Durand M, Roche H, Delozier T, Battista C, Fargeot P, Spaeth D, Bachelot T, Poiget E, Monnot F, Tanguy ML, Cure H. Pegase 03: a prospective randomized phase III trial of FEC with or without high-dose thiotepa, cyclophosphamide and autologous stem cell transplantation in first-line treatment of metastatic breast cancer. Bone Marrow Transplant. 2008 Mar;41(6):555-62. doi: 10.1038/sj.bmt.1705935. Epub 2007 Nov 26.
citation: Biron P, Durand M, Roche H, et al.: High dose thiotepa (TTP), cyclophosphamide (CPM) and stem cell transplantation after 4 FEC 100 compared with 4 FEC alone allowed a better disease free survival but the same overall survival in first line chemotherapy for metastatic breast cancer: results of the PEGASE 03 French protocole. [Abstract] Proceedings of the American Society of Clinical Oncology A-167, 2002.