High Dose Chemotherapy Plus Peripheral Stem Cell Transplantation Compared With Standard Therapy in Treating Women With Locally Recurrent or Metastatic Breast Cancer

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002870
• Other study ID #: PEGASE03
• Secondary ID: FRE-FNCLCC-PEGAS
• Status: Completed
• Phase: Phase 3
• First received: November 1, 1999
• Last updated: December 14, 2014
• Start date: December 1994
• Est. completion date: January 2002

Study information

• Verified date: December 2014
• Source: UNICANCER
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 180
• Est. completion date: January 2002
• Est. primary completion date: January 2002
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 59 Years

Eligibility

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

Study Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Biological:
• filgrastim

Drug:
• cyclophosphamide

• epirubicin hydrochloride

• fluorouracil

• thiotepa

Procedure:
• peripheral blood stem cell transplantation

Locations

Country	Name	City	State
France	Centre Paul Papin	Angers
France	CHR de Besancon - Hopital Jean Minjoz	Besancon
France	Clinique Saint Vincent	Besancon
France	Institut Bergonie	Bordeaux
France	C.H. Bourg En Bresse	Bourg En Bresse
France	C.H.U. de Brest	Brest
France	Centre Hospitalier General	Brive
France	Centre Regional Francois Baclesse	Caen
France	Centre Jean Perrin	Clermont-Ferrand
France	Hopital Louis Pasteur	Colmar
France	Centre de Lute Contre le Cancer,Georges-Francois Leclerc	Dijon
France	Institut Prive de Cancerologie	Grenoble
France	Centre Oscar Lambret	Lille
France	Centre Leon Berard	Lyon
France	Institut J. Paoli and I. Calmettes	Marseille
France	Hopital Notre-Dame de Bon Secours	Metz
France	Hopital Sainte Blandine	Metz
France	Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle	Montpellier
France	Centre Antoine Lacassagne	Nice
France	Federation Nationale des Centres de Lutte Contre le Cancer	Paris
France	Hopital Saint-Louis	Paris
France	Hopital Tenon	Paris
France	Hopital Haut Leveque	Pessac
France	Hopital Jean Bernard	Poitiers
France	Institut Jean Godinot	Reims
France	Centre Eugene Marquis	Rennes
France	C.H.U. Saint Etienne Hospital Nord	Saint Etienne
France	Hopitaux Universitaire de Strasbourg	Strasbourg
France	Institut Claudius Regaud	Toulouse
France	Centre Hospitalier Universitaire Bretonneau de Tours	Tours
France	Centre Alexis Vautrin	Vandoeuvre-les-Nancy
France	CHRU de Nancy - Hopitaux de Brabois	Vandoeuvre-Les-Nancy

Sponsors (1)

Lead Sponsor	Collaborator
UNICANCER

Country where clinical trial is conducted

France, 

References & Publications (2)

Biron P, Durand M, Roché H, Delozier T, Battista C, Fargeot P, Spaeth D, Bachelot T, Poiget E, Monnot F, Tanguy ML, Curé H. Pegase 03: a prospective randomized phase III trial of FEC with or without high-dose thiotepa, cyclophosphamide and autologous stem — View 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 fo

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease free survival		5 years