Combination Chemotherapy in Treating Women With Resected Breast Cancer

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

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.

Study Overview

• Status: Unknown
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: cyclophosphamide; Drug: docetaxel; Drug: fluorouracil; Radiation: radiation therapy; Drug: methotrexate; Procedure: adjuvant therapy; Drug: tamoxifen citrate; Drug: epirubicin hydrochloride; Drug: CMF regimen

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.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, B-3000
    • U.Z. Gasthuisberg
• United Kingdom
  • England
    • Barnstaple, England, United Kingdom, EX31 4JB
      • North Devon District Hospital
    • Bath, England, United Kingdom, BA1 3NG
      • Royal United Hospital
    • Birmingham, England, United Kingdom, B15 2TH
      • Queen Elizabeth Hospital at University of Birmingham
    • Birmingham, England, United Kingdom, B18 7QH
      • City Hospital - Birmingham
    • Blackpool, England, United Kingdom, FY3 8NR
      • Blackpool Victoria Hospital
    • Boston, England, United Kingdom, PE21 9QT
      • Pilgrim Hospital
    • Bradford, England, United Kingdom, BD9 6RJ
      • Bradford Hospitals NHS Trust
    • Brighton, England, United Kingdom, BN2 5BF
      • Royal Sussex County Hospital
    • Bristol, England, United Kingdom, BS2 8ED
      • Bristol Haematology and Oncology centre
    • Bury St. Edmunds, England, United Kingdom, IP33 2QZ
      • West Suffolk Hospital
    • Cambridge, England, United Kingdom, CB2 2QQ
      • Addenbrooke's Hospital at Cambridge University Hospitals NHS Foundation Trust
    • Chelmsford, Essex, England, United Kingdom, CM1 5ET
      • Broomfield Hospital
    • Cheltenham, England, United Kingdom, GL53 7AN
      • Cheltenham General Hospital
    • Colchester, England, United Kingdom, C03 3NB
      • Essex County Hospital
    • Coventry, England, United Kingdom, CV2 2DX
      • Walsgrave Hospital
    • Derby, England, United Kingdom, DE1 2QY
      • Derbyshire Royal Infirmary
    • Exeter, England, United Kingdom, EX2 5DW
      • Royal Devon and Exeter Hospital
    • Grimsby, England, United Kingdom, DN33 2BA
      • Diana Princess of Wales Hospital
    • Guildford, England, United Kingdom, GU2 5XX
      • St. Luke's Cancer Centre at Royal Surrey County Hospital
    • Hampstead, London, England, United Kingdom, NW3 2QG
      • Royal Free and University College Medical School
    • Huddersfield, West Yorks, England, United Kingdom, HD3 3EA
      • Huddersfield Royal Infirmary
    • Hull, England, United Kingdom, HU8 9HE
      • Princess Royal Hospital
    • Ipswich, England, United Kingdom, IP4 5PD
      • Ipswich Hospital NHS Trust
    • King's Lynn, England, United Kingdom, PE30 4ET
      • Queen Elizabeth Hospital
    • Leeds, England, United Kingdom, LS9 7TF
      • Leeds Cancer Centre at St. James's University Hospital
    • Leeds, England, United Kingdom, LS16 6QB
      • Cookridge Hospital at Leeds Teaching Hospital NHS Trust
    • Leicester, England, United Kingdom, LE1 5WW
      • Leicester Royal Infirmary
    • London, England, United Kingdom, EC1A 7BE
      • Saint Bartholomew's Hospital
    • London, England, United Kingdom, SW17 ORE
      • St. Georges Hospital Medical School
    • London, England, United Kingdom, W6 8RF
      • Charing Cross Hospital
    • London, England, United Kingdom, SE1 9RT
      • Guy's Hospital
    • London, England, United Kingdom, WIT 3AA
      • Meyerstein Institute of Oncology at University College of London Hospitals
    • Maidstone, England, United Kingdom, ME16 9QQ
      • Maidstone Hospital
    • Manchester, England, United Kingdom, M20 4BX
      • Christie Hospital N.H.S. Trust
    • Merseyside, England, United Kingdom, CH63 4JY
      • Clatterbridge Centre for Oncology NHS Trust
    • Newcastle Upon Tyne, England, United Kingdom, NE4 6BE
      • Northern Centre for Cancer Treatment at Newcastle General Hospital
    • Northampton, England, United Kingdom, NN6 8BJ
      • Northampton General Hospital NHS Trust
    • Northwood, England, United Kingdom, HA6 2RN
      • Mount Vernon Hospital
    • Oxford, England, United Kingdom, 0X3 9DU
      • Oxford Radcliffe Hospital
    • Peterborough, England, United Kingdom, PE3 6DA
      • Peterborough Hospitals Trust
    • Portsmouth Hants, England, United Kingdom, PO3 6AD
      • Portsmouth Oncology Centre at Saint Mary's Hospital
    • Preston, England, United Kingdom, PR2 9HT
      • Royal Preston Hospital
    • Reading, England, United Kingdom, RG1 5AN
      • Berkshire Cancer Centre at Royal Berkshire Hospital
    • Redditch, Worcestershire, England, United Kingdom, B98 7UB
      • Alexandra Healthcare NHS
    • Romford, England, United Kingdom, RM7 OBE
      • Oldchurch Hospital
    • Salisbury, England, United Kingdom, SP2 8BJ
      • Salisbury District Hospital
    • Scunthorpe, England, United Kingdom, DN15 7BH
      • Scunthorpe General Hospital
    • Sheffield, England, United Kingdom, S1O 2SJ
      • Cancer Research Centre at Weston Park Hospital
    • Shrewsbury, England, United Kingdom, SY3 8XQ
      • Royal Shrewsbury Hospital
    • Southampton, England, United Kingdom, SO14 0YG
      • Royal South Hants Hospital
    • Stoke-On-Trent, England, United Kingdom, ST4 7LN
      • North Staffs Royal Infirmary
    • Sutton, England, United Kingdom, SM2 5PT
      • Royal Marsden NHS Foundation Trust - Surrey
    • Taunton Somerset, England, United Kingdom, TA1 5DA
      • Taunton and Somerset Hospital
    • Torquay Devon, England, United Kingdom, TQ2 7AA
      • Torbay Hospital
    • Westcliff-On-Sea, England, United Kingdom, SS0 0RY
      • Southend NHS Trust Hospital
    • Wolverhampton, England, United Kingdom, WV10 0QP
      • New Cross Hospital
  • Northern Ireland
    • Belfast, Northern Ireland, United Kingdom, BT8 8JR
      • Belfast City Hospital Trust Incorporating Belvoir Park Hospital
  • Scotland
    • Aberdeen, Scotland, United Kingdom, AB25 2ZN
      • Aberdeen Royal Infirmary
    • Dundee, Scotland, United Kingdom, DD1 9SY
      • Ninewells Hospital and Medical School
    • East Kilbride, Scotland, United Kingdom, G75 8RG
      • Hairmyres Hospital
    • Edinburgh, Scotland, United Kingdom, EH4 2XU
      • Western General Hospital
    • Glasgow, Scotland, United Kingdom, G4 0SF
      • Royal Infirmary - Castle
    • Glasgow, Scotland, United Kingdom, G11 6NT
      • Beatson Oncology Centre
    • Inverness, Scotland, United Kingdom, 1V2 3UJ
      • Raigmore Hospital
  • Wales
    • Aberystwyth, Wales, United Kingdom, SY23 1ER
      • Bronglais General Hospital - Ceredigion and Mid Wales NHS trust
    • Cardiff, Wales, United Kingdom, CF14 2TL
      • Velindre Cancer Center at Velinde Hospital
    • Rhyl, Denbighshire, Wales, United Kingdom, LL 18 5UJ
      • Glan Clywd District General Hospital
    • Swansea, Wales, United Kingdom, SA 2 8QA
      • Singleton Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized

Collaborators and Investigators

• Sponsor: Institute of Cancer Research, United Kingdom
• Investigators: Study Chair: Jane Banerji, Institute of Cancer Research, United Kingdom

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: February 1, 2001

Study Registration Dates

• First Submitted: April 9, 2002
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): February 9, 2009
• Last Update Submitted That Met QC Criteria: February 6, 2009
• Last Verified: June 1, 2005

More Information

Terms related to this study

• Keywords: stage II breast cancer; stage I breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Dermatologic Agents; Antibiotics, Antineoplastic; Hormone Antagonists; Bone Density Conservation Agents; Estrogen Antagonists; Reproductive Control Agents; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Docetaxel; Cyclophosphamide; Fluorouracil; Epirubicin; Methotrexate; Tamoxifen
• Other Study ID Numbers: CDR0000069311; ICR-TACT; EU-20109