Standard Chemotherapy Compared With High-Dose Combination Chemotherapy and Peripheral Stem Cell Transplantation in Treating Women With Breast Cancer

Breast Cancer Clinical Trial

Official title:

PROSPECTIVE RANDOMISED EVALUATION OF HIGH-INTENSITY CHEMOTHERAPY WITH PERIPHERAL BLOOD PROGENITOR SUPPORT IN PATIENTS WITH HIGH RISK BREAST CANCER

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002755
• Other study ID #: CDR0000064692
• Secondary ID: SCTN-BR9405EU-95
• Status: Completed
• Phase: Phase 3
• First received: November 1, 1999
• Last updated: November 5, 2013
• Start date: November 1995
• Est. completion date: June 1999

Study information

• Verified date: May 2007
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• 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. Peripheral stem cell transplantation may allow doctors to give higher doses of chemotherapy drugs and kill more tumor cells. It is not yet known which treatment regimen is more effective for breast cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of standard cyclophosphamide, methotrexate, and fluorouracil with that of high-dose combination chemotherapy plus peripheral stem cell transplantation in treating women who have stage II or stage IIIA breast cancer.

Description:

OBJECTIVES: I. Compare the efficacy of high dose cyclophosphamide and thiotepa with peripheral blood stem cell support vs conventional cyclophosphamide, methotrexate, and fluorouracil (CMF), both following doxorubicin induction, in women with high risk breast cancer.

OUTLINE: This is a randomized, multicenter study. Patients are stratified by the number of positive axillary nodes (4-9 vs at least 10) and by center. Patients are randomized to one of two treatment arms. Arm I: Patients receive induction therapy consisting of doxorubicin IV every 3 weeks for 4 courses followed by consolidation therapy consisting of cyclophosphamide IV, methotrexate IV, and fluorouracil IV every 3 weeks for 8 courses. At week 4 of consolidation therapy, patients receive radiotherapy to the breast, chest wall, and axilla over 3-5 weeks or as appropriate. Following recovery from consolidation therapy, patients receive maintenance therapy consisting of oral tamoxifen daily for 5 years. Arm II: Patients receive induction therapy as in arm I followed by consolidation therapy consisting of stem cell mobilization with high dose cyclophosphamide IV over 2 hours and filgrastim (G-CSF) subcutaneously beginning 24 hours after cyclophosphamide and continuing until blood counts recover. At 13-28 days following peripheral blood stem cell (PBSC) collection and/or autologous bone marrow collection, patients undergo chemoablation consisting of thiotepa IV and cyclophosphamide IV continuously over 4 days followed 72 hours later by PBSC infusion with or without autologous bone marrow. Following hematologic recovery, patients receive radiotherapy and maintenance therapy as in arm I. Patients are followed every 6 months for 2 years, then annually.

PROJECTED ACCRUAL: More than 600 patients will be accrued for this study over 5 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 600
• Est. completion date: June 1999
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS: Histologically confirmed stage II or IIIA breast cancer with at least 4 positive axillary nodes Definitive resection required, preferably within 4 weeks prior to entry No overt residual axillary nodal carcinoma after surgery Hormone receptor status: Not specified

PATIENT CHARACTERISTICS: Age: Over 18 Sex: Female Menopausal status: Not specified Performance status: ECOG 0 or 1 Hematopoietic: Absolute neutrophil count greater than 1,500/mm3 Platelet count greater than 100,000/mm3 Hemoglobin greater than 9 g/dL PT and aPTT normal Hepatic: Bilirubin normal (unless benign congenital hyperbilirubinemia) Normal liver biopsy required in patients with active hepatitis B or C Renal: Creatinine normal Cardiovascular: No active heart disease Normal wall motion on MUGA or echocardiogram Other: Adequate nutritional status (i.e., more than 1,000 calories/day orally) HIV negative No serious medical or psychiatric disease No second malignancy except: Basal cell skin cancer Carinoma in situ of the cervix Not pregnant Negative pregnancy test

PRIOR CONCURRENT THERAPY: At least 2 weeks since major surgery

Study Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Biological:
• filgrastim

Drug:
• CMF regimen

• cyclophosphamide

• doxorubicin hydrochloride

• fluorouracil

• methotrexate

• tamoxifen citrate

• thiotepa

Procedure:
• autologous bone marrow transplantation

• peripheral blood stem cell transplantation

Radiation:
• low-LET cobalt-60 gamma ray therapy

• low-LET electron therapy

• low-LET photon therapy

Locations

Country	Name	City	State
Ireland	St. Vincent's Hospital	Dublin
United Kingdom	Aberdeen Royal Infirmary	Aberdeen	Scotland
United Kingdom	Addenbrooke's NHS Trust	Cambridge	England
United Kingdom	Velindre Hospital	Cardiff	Wales
United Kingdom	Cheltenham General Hospital	Cheltenham	England
United Kingdom	Royal Infirmary	Edinburgh	Scotland
United Kingdom	Western General Hospital	Edinburgh	Scotland
United Kingdom	Royal Devon and Exeter Hospital	Exeter	England
United Kingdom	Beatson Oncology Centre	Glasgow	Scotland
United Kingdom	Royal Infirmary	Glasgow	Scotland
United Kingdom	Royal Free Hospital	Hampstead, London	England
United Kingdom	Northwick Park Hospital	Harrow	England
United Kingdom	Huddersfield Royal Infirmary	Huddersfield, West Yorks	England
United Kingdom	St. James's Hospital	Leeds	England
United Kingdom	Middlesex Hospital- Meyerstein Institute	London	England
United Kingdom	St. George's Hospital	London	England
United Kingdom	Newcastle General Hospital	Newcastle Upon Tyne	England
United Kingdom	Nottingham City Hospital NHS Trust	Nottingham	England
United Kingdom	Derriford Hospital	Plymouth	England
United Kingdom	Weston Park Hospital	Sheffield	England
United Kingdom	Royal South Hants Hospital	Southampton	England

Sponsors (1)

Lead Sponsor	Collaborator
Scottish Cancer Therapy Network

Countries where clinical trial is conducted

Ireland,  United Kingdom,