Clinical trial NCT00033683: Combination Chemotherapy in Treating Women With Resected Breast Cancer
Official title: A Randomised Trial Of Standard Anthracycline-Based Chemotherapy With Fluorouracil, Epirubicin And Cyclophosphamide (FEC) Or Epirubicin And CMF (Epi-CMF) Versus FEC Followed By Sequential Docetaxel As Adjuvant Treatment For Women With Early Breast Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Breast Cancer
Keywords: stage I breast cancer
stage II breast cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Sex: FEMALE
Minimum age (years): 18
Standard ages: 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 and giving them after surgery may kill any tumor cells remaining after surgery. It is not yet known which combination chemotherapy regimen is more effective in treating resected stage I or stage II breast cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of different combination chemotherapy regimens in treating women who have resected stage I or stage II breast cancer.

Detailed description: OBJECTIVES:

* Compare the disease-free and overall survival of women with completely resected stage I or II breast cancer adjuvantly treated with fluorouracil, epirubicin, and cyclophosphamide (FEC) or epirubicin followed by cyclophosphamide, methotrexate, and fluorouracil (EPI-CMF) versus FEC followed by sequential docetaxel.
* Compare the acute toxicity of these regimens in these patients.
* Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, estrogen receptor status (positive vs negative), and nodal status. Within 8 weeks after definitive surgery, patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients are assigned to 1 of 2 standard adjuvant chemotherapy regimens.

  * Regimen A: Patients receive fluorouracil, epirubicin, and cyclophosphamide (FEC) IV on day 1. Treatment repeats every 3 weeks for 8 courses.
  * Regimen B: Patients receive epirubicin IV on day 1. Treatment repeats every 3 weeks for 4 courses. Patients then receive cyclophosphamide orally on days 1-14 or IV on days 1 and 8 and methotrexate IV and fluorouracil IV on days 1 and 8 (CMF). Treatment with CMF repeats every 4 weeks for 4 courses.
* Arm II: Patients receive 4 courses of adjuvant chemotherapy with FEC as in arm I, regimen A. Patients then receive sequential docetaxel IV over 1 hour once every 3 weeks for 4 courses.

Beginning within 4 weeks after completion of adjuvant chemotherapy, patients who are not concurrently enrolled in the Standardization of Breast Radiotherapy (START) trial receive localized radiotherapy once daily, 5 days a week, for 3-5 weeks, according to local practice.

Beginning within 4 weeks after completion of adjuvant chemotherapy, patients who are estrogen receptor and/or progesterone receptor positive receive oral tamoxifen once daily for at least 5 years.

Quality of life is assessed at baseline, before course 5, at 3-4 weeks after course 8, and then at 9, 12, 18, and 24 months after initiation of adjuvant chemotherapy.

Patients are followed every 3 months for 2 years and then every 6 months thereafter.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 3,340 patients (1,670 per treatment arm) will be accrued for this study within 2 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed completely resected, invasive breast cancer for which adjuvant chemotherapy is indicated
* No clinical or radiological evidence of locoregional or metastatic disease
* No locally advanced tumors at diagnosis, indicated by any of the following:

  * Fixed tumors
  * Peau d'orange skin changes
  * Skin ulceration
  * Inflammatory changes (T4 or T3b, N2 disease)
* No male breast cancer
* No prior invasive breast cancer or bilateral breast cancer
* Prior ductal carcinoma in situ or lobular carcinoma in situ is allowed
* Must begin study chemotherapy within 8 weeks after definitive surgery
* Hormone receptor status:

  * Estrogen receptor and progesterone receptor status known

PATIENT CHARACTERISTICS:

Age:

* Over 18

Sex:

* Female

Menopausal status:

* Not specified

Performance status:

* WHO 0-1

Life expectancy:

* At least 2 years

Hematopoietic:

* WBC at least 3,000/mm\^3
* Platelet count at least 100,000/mm\^3
* Hemoglobin at least 9 g/dL

Hepatic:

* Bilirubin normal
* AST no greater than 1.5 times normal
* Alkaline phosphatase no greater than 1.5 times normal

Renal:

* Creatinine no greater than 1.5 times normal

Cardiovascular:

* No myocardial infarction within the past 6 months
* No congestive heart failure

Other:

* Not pregnant or nursing
* Fertile patients must use effective contraception
* No other invasive malignancy within the past 10 years except surgically cured nonmelanoma skin cancer or carcinoma in situ of the cervix
* No other serious medical illness that would limit life expectancy
* No psychiatric condition that would preclude informed consent
* No active uncontrolled bacterial, viral, or fungal infection

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* No prior biologic therapy

Chemotherapy:

* See Disease Characteristics
* No prior cytotoxic chemotherapy

Endocrine therapy:

* No concurrent hormonal therapy (e.g., tamoxifen) during study chemotherapy
* No concurrent hormone replacement therapy

Radiotherapy:

* No prior radiotherapy

Surgery:

* See Disease Characteristics

Other:

* At least 4 weeks since any prior unlicensed drugs
* No other concurrent experimental drugs

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: U.Z. Gasthuisberg
city: Barnstaple
country: United Kingdom
facility: North Devon District Hospital
state: England
city: Bath
country: United Kingdom
facility: Royal United Hospital
state: England
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital at University of Birmingham
state: England
city: Birmingham
country: United Kingdom
facility: City Hospital - Birmingham
state: England
city: Blackpool
country: United Kingdom
facility: Blackpool Victoria Hospital
state: England
city: Boston
country: United Kingdom
facility: Pilgrim Hospital
state: England
city: Bradford
country: United Kingdom
facility: Bradford Hospitals NHS Trust
state: England
city: Brighton
country: United Kingdom
facility: Royal Sussex County Hospital
state: England
city: Bristol
country: United Kingdom
facility: Bristol Haematology and Oncology Centre
state: England
city: Bury St. Edmunds
country: United Kingdom
facility: West Suffolk Hospital
state: England
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital at Cambridge University Hospitals NHS Foundation Trust
state: England
city: Chelmsford, Essex
country: United Kingdom
facility: Broomfield Hospital
state: England
city: Cheltenham
country: United Kingdom
facility: Cheltenham General Hospital
state: England
city: Colchester
country: United Kingdom
facility: Essex County Hospital
state: England
city: Coventry
country: United Kingdom
facility: Walsgrave Hospital
state: England
city: Derby
country: United Kingdom
facility: Derbyshire Royal Infirmary
state: England
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital
state: England
city: Grimsby
country: United Kingdom
facility: Diana Princess of Wales Hospital
state: England
city: Guildford
country: United Kingdom
facility: St. Luke's Cancer Centre at Royal Surrey County Hospital
state: England
city: Hampstead, London
country: United Kingdom
facility: Royal Free and University College Medical School
state: England
city: Huddersfield, West Yorks
country: United Kingdom
facility: Huddersfield Royal Infirmary
state: England
city: Hull
country: United Kingdom
facility: Princess Royal Hospital
state: England
city: Ipswich
country: United Kingdom
facility: Ipswich Hospital NHS Trust
state: England
city: King's Lynn
country: United Kingdom
facility: Queen Elizabeth Hospital
state: England
city: Leeds
country: United Kingdom
facility: Cookridge Hospital at Leeds Teaching Hospital NHS Trust
state: England
city: Leeds
country: United Kingdom
facility: Leeds Cancer Centre at St. James's University Hospital
state: England
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
state: England
city: London
country: United Kingdom
facility: Saint Bartholomew's Hospital
state: England
city: London
country: United Kingdom
facility: Guy's Hospital
state: England
city: London
country: United Kingdom
facility: St. Georges Hospital Medical School
state: England
city: London
country: United Kingdom
facility: Charing Cross Hospital
state: England
city: London
country: United Kingdom
facility: Meyerstein Institute of Oncology at University College of London Hospitals
state: England
city: Maidstone
country: United Kingdom
facility: Maidstone Hospital
state: England
city: Manchester
country: United Kingdom
facility: Christie Hospital N.H.S. Trust
state: England
city: Merseyside
country: United Kingdom
facility: Clatterbridge Centre for Oncology NHS Trust
state: England
city: Newcastle Upon Tyne
country: United Kingdom
facility: Northern Centre for Cancer Treatment at Newcastle General Hospital
state: England
city: Northampton
country: United Kingdom
facility: Northampton General Hospital NHS Trust
state: England
city: Northwood
country: United Kingdom
facility: Mount Vernon Hospital
state: England
city: Oxford
country: United Kingdom
facility: Oxford Radcliffe Hospital
state: England
city: Peterborough
country: United Kingdom
facility: Peterborough Hospitals Trust
state: England
city: Portsmouth Hants
country: United Kingdom
facility: Portsmouth Oncology Centre at Saint Mary's Hospital
state: England
city: Preston
country: United Kingdom
facility: Royal Preston Hospital
state: England
city: Reading
country: United Kingdom
facility: Berkshire Cancer Centre at Royal Berkshire Hospital
state: England
city: Redditch, Worcestershire
country: United Kingdom
facility: Alexandra Healthcare NHS
state: England
city: Romford
country: United Kingdom
facility: Oldchurch Hospital
state: England
city: Salisbury
country: United Kingdom
facility: Salisbury District Hospital
state: England
city: Scunthorpe
country: United Kingdom
facility: Scunthorpe General Hospital
state: England
city: Sheffield
country: United Kingdom
facility: Cancer Research Centre at Weston Park Hospital
state: England
city: Shrewsbury
country: United Kingdom
facility: Royal Shrewsbury Hospital
state: England
city: Southampton
country: United Kingdom
facility: Royal South Hants Hospital
state: England
city: Stoke-On-Trent
country: United Kingdom
facility: North Staffs Royal Infirmary
state: England
city: Sutton
country: United Kingdom
facility: Royal Marsden NHS Foundation Trust - Surrey
state: England
city: Taunton Somerset
country: United Kingdom
facility: Taunton and Somerset Hospital
state: England
city: Torquay Devon
country: United Kingdom
facility: Torbay Hospital
state: England
city: Westcliff-On-Sea
country: United Kingdom
facility: Southend NHS Trust Hospital
state: England
city: Wolverhampton
country: United Kingdom
facility: New Cross Hospital
state: England
city: Belfast
country: United Kingdom
facility: Belfast City Hospital Trust Incorporating Belvoir Park Hospital
state: Northern Ireland
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
state: Scotland
city: Dundee
country: United Kingdom
facility: Ninewells Hospital and Medical School
state: Scotland
city: East Kilbride
country: United Kingdom
facility: Hairmyres Hospital
state: Scotland
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
state: Scotland
city: Glasgow
country: United Kingdom
facility: Beatson Oncology Centre
state: Scotland
city: Glasgow
country: United Kingdom
facility: Royal Infirmary - Castle
state: Scotland
city: Inverness
country: United Kingdom
facility: Raigmore Hospital
state: Scotland
city: Aberystwyth
country: United Kingdom
facility: Bronglais General Hospital - Ceredigion and Mid Wales NHS trust
state: Wales
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Center at Velinde Hospital
state: Wales
city: Rhyl, Denbighshire
country: United Kingdom
facility: Glan Clywd District General Hospital
state: Wales
city: Swansea
country: United Kingdom
facility: Singleton Hospital
state: Wales
Study officials:
affiliation: Institute of Cancer Research, United Kingdom
name: Jane Banerji
role: STUDY_CHAIR
References:
citation: Hopwood P, Ellis P, Barrett-Lee P, et al.: Impact on quality of life (QL) during chemotherapy (CT) of FEC-T compared to FEC or E-CMF: results from the UK NCRI taxotere as adjuvant chemotherapy trial (TACT). [Abstract] J Clin Oncol 23 (Suppl 16): A-661, 43s, 2005.
citation: Kilburn LS, Aresu M, Banerji J, Barrett-Lee P, Ellis P, Bliss JM. Can routine data be used to support cancer clinical trials? A historical baseline on which to build: retrospective linkage of data from the TACT (CRUK 01/001) breast cancer trial and the National Cancer Data Repository. Trials. 2017 Nov 23;18(1):561. doi: 10.1186/s13063-017-2308-6.