Clinical trial NCT00301925: Combination Chemotherapy in Treating Patients With Early Stage Breast Cancer That Has Been Removed By Surgery
Official title: Trial of Accelerated Adjuvant Chemotherapy With Capecitabine in Early Breast Cancer (TACT2)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Breast Cancer
Keywords: stage I breast cancer
stage II breast cancer
stage IIIA breast cancer
male breast cancer
Lead sponsor: Institute of Cancer Research, United Kingdom
Sponsor class: OTHER
First posted: 2006-03-13
Enrollment: 4400
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Giving combination chemotherapy after surgery may kill any remaining tumor cells. It is not yet known which combination chemotherapy regimen is more effective in treating early stage breast cancer that has been removed by surgery.

PURPOSE: This randomized phase III trial is studying four different combination chemotherapy regimens to compare how well they work in treating patients with early stage breast cancer that has been removed by surgery.

Detailed description: OBJECTIVES:

Primary

* Compare the disease-free survival (DFS) of patients with completely resected early stage breast cancer receiving 1 of 2 different schedules of adjuvant chemotherapy comprising epirubicin, cyclophosphamide, methotrexate, and fluorouracil versus 1 of 2 different schedules of adjuvant chemotherapy comprising epirubicin and capecitabine.

Secondary

* Compare overall survival (OS) and distant disease-free survival (DFS).
* Compare the tolerability (including serious adverse events \[SAE\], dose-intensity, and toxicity) of these regimens.
* Determine the detailed toxicity of these regimens.
* Determine the quality of life of a subset of these patients.

OUTLINE: This is a multi-center, randomized study. Patients are stratified according to participating center, nodal status (N0 vs N1-3 vs N≥ 4), age (≤ 50 years vs \> 50 years), and estrogen receptor (ER) status (negative vs positive). Patients are randomized to 1 of 4 treatment arms.

* Arm I: Patients receive epirubicin on day 1. Treatment repeats every 3 weeks for 4 courses. Patients then receive cyclophosphamide orally once daily on days 1-14 or IV on days 1 and 8 and methotrexate and fluorouracil on days 1 and 8. Treatment repeats every 28 days for 4 courses.
* Arm II: Patients receive epirubicin on day 1 and pegfilgrastim on day 2. Treatment repeats every 2 weeks for 4 courses. Patients then receive cyclophosphamide, methotrexate and fluorouracil as in arm I.
* Arm III: Patients receive epirubicin as in arm I. Patients then receive oral capecitabine twice daily on days 1-14. Treatment with capecitabine repeats every 3 weeks for 4 courses.
* Arm IV: Patients receive epirubicin and pegfilgrastim as in arm II. Patients then receive capecitabine as in arm III.

In all arms, treatment continues in the absence of unacceptable toxicity.

Beginning 3-6 months later, all patients may undergo radiotherapy at the discretion of the principal investigator. Patients with ER- and/or progesterone receptor-positive disease then receive tamoxifen citrate or an aromatase inhibitor for up to 5 years.

Quality of life is assessed in a cohort of 1,000 patients in week 6, week 8 or 12, and week 20 or 24 during treatment and then at 12 and 24 months after randomization.

After completion of study therapy, patients are followed every 6 months for 2 years and then annually for at least 10 years.

Peer Reviewed and Funded or Endorsed by Cancer Research UK.

PROJECTED ACCRUAL: A total of 4,400 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histological diagnosis of invasive breast carcinoma

  * Cytological proof of malignancy alone is not sufficient
  * Early stage disease (T0-3, N0-2, M0) without clinical suspicion or evidence of distant metastases on routine staging
  * No locally advanced breast cancer (T4 and/or N3 disease)
* Completely resected disease by breast-conserving surgery with axillary node clearance or modified radical mastectomy within the past 4-8 weeks

  * Negative surgical margins required, unless either of the following are true:

    * Deep surgical margins after full thickness resection
    * Noninvasive cancer at surgical margins for which a mastectomy is planned after completion of study chemotherapy
  * No contraindication for or refusal of postoperative radiotherapy in patients who underwent prior breast-conserving surgery
* Definite indication for adjuvant chemotherapy
* No prior or current invasive breast cancer or bilateral breast cancer

  * Prior surgically-treated ductal carcinoma in situ or lobular carcinoma in situ allowed
* Hormone receptor status:

  * Estrogen receptor- and/or progesterone receptor-positive or -negative tumor

PATIENT CHARACTERISTICS:

* Sex: male or female
* Menopausal status: premenopausal or postmenopausal
* No previous malignancy except basal cell carcinoma, carcinoma in situ of the cervix, or any cancer from which the patient has been disease-free for 10 years and for which treatment consisted solely of resection
* ECOG status 0 or 1
* Hemoglobin \> 9 g/dL
* WBC \> 3,000/mm³
* Platelet count \> 10,000/mm³
* Bilirubin normal (unless due to known Gilbert's disease)
* AST and ALT ≤ 1.5 times upper limit of normal (ULN)
* Albumin normal
* Creatinine ≤ 1.5 times ULN
* Creatinine clearance \> 50 mL/min
* No active, uncontrolled infection
* Not pregnant or nursing
* Fertile patients must use effective contraception
* No concurrent medical, psychiatric, or geographic problems that might prevent completion of treatment or follow-up
* Available for a minimum of 5 years' follow-up
* No known serious viral infection such as active hepatitis B, hepatitis C, or HIV
* No significant cardiac disease, such as impaired left ventricular function or active angina requiring regular anti-anginal medication and/or resulting in restricted physical activity
* No history of significant renal impairment or disease

PRIOR CONCURRENT THERAPY:

* No simultaneous participation in the active intervention phase of another treatment trial
* Not being approached or recruited for another trial within 2 months of study entry
* No previous chemotherapy, hormonal therapy or radiotherapy for the treatment of pre-invasive or invasive cancer except for either of the following:

  * Previous radiotherapy for basal cell carcinoma
  * Previous preoperative endocrine therapy, provided there was no evidence of progression during this therapy, it lasted for less than 6 weeks in duration, and it was stopped at least one month prior to trial entry
* Concurrent luteinizing hormone-releasing hormone analog therapy allowed for premenopausal patients
* More than 4 weeks since prior hormone replacement therapy (HRT) or pre-operative endocrine therapy
* No prior breast conserving surgery if there is a contradiction for or refusal of postoperative radiotherapy

Primary outcomes:
measure: Disease-free survival (DFS) at 5 years
Secondary outcomes:
measure: Overall survival at 5 years
measure: Distant DFS at 5 years
measure: Tolerability (including serious adverse events, dose-intensity, and toxicity)
measure: Detailed toxicity
measure: Quality of life
Other outcomes:
Locations:
city: Ashford-Kent
country: United Kingdom
facility: William Harvey Hospital
state: England
city: Ashington
country: United Kingdom
facility: Wansbeck General Hospital
state: England
city: Ashton-Under-Lyne
country: United Kingdom
facility: Tameside General Hospital
state: England
city: Barnstaple
country: United Kingdom
facility: North Devon District Hospital
state: England
city: Barrow in Furness
country: United Kingdom
facility: Furness General Hospital
state: England
city: Basildon
country: United Kingdom
facility: Basildon University Hospital
state: England
city: Basingstoke
country: United Kingdom
facility: Basingstoke and North Hampshire NHS Foundation Trust
state: England
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust
state: England
city: Birmingham
country: United Kingdom
facility: City Hospital - Birmingham
state: England
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
state: England
city: Blackburn
country: United Kingdom
facility: Royal Blackburn Hospital
state: England
city: Blackpool
country: United Kingdom
facility: Blackpool Victoria Hospital
state: England
city: Bolton, Lancashire
country: United Kingdom
facility: Royal Bolton Hospital
state: England
city: Bradford
country: United Kingdom
facility: Bradford Royal Infirmary
state: England
city: Brighton
country: United Kingdom
facility: Sussex Cancer Centre at Royal Sussex County Hospital
state: England
city: Bristol
country: United Kingdom
facility: Bristol Haematology and Oncology Centre
state: England
city: Broomefield
country: United Kingdom
facility: Broomfield Hospital
state: England
city: Burnley
country: United Kingdom
facility: Burnley General Hospital
state: England
city: Burton-upon-Trent
country: United Kingdom
facility: Queen's Hospital
state: England
city: Bury St. Edmunds
country: United Kingdom
facility: West Suffolk Hospital
state: England
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
state: England
city: Canterbury
country: United Kingdom
facility: Kent and Canterbury Hospital
state: England
city: Cheltenham
country: United Kingdom
facility: Cheltenham General Hospital
state: England
city: Cheshire
country: United Kingdom
facility: Halton Hospital
state: England
city: Chesterfield
country: United Kingdom
facility: Chesterfield Royal Hospital
state: England
city: Chichester
country: United Kingdom
facility: Saint Richards 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: Dartford Kent
country: United Kingdom
facility: Darent Valley Hospital
state: England
city: Derby
country: United Kingdom
facility: Derbyshire Royal Infirmary
state: England
city: Dewsbury
country: United Kingdom
facility: Dewsbury and District Hospital
state: England
city: Doncaster
country: United Kingdom
facility: Doncaster Royal Infirmary
state: England
city: Dudley
country: United Kingdom
facility: Russells Hall Hospital
state: England
city: Durham
country: United Kingdom
facility: University Hospital of North Durham
state: England
city: Eastbourne
country: United Kingdom
facility: Eastbourne District General Hospital
state: England
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital
state: England
city: Gateshead
country: United Kingdom
facility: Queen Elizabeth Hospital
state: England
city: Gloucester
country: United Kingdom
facility: Gloucestershire Royal 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: UCL Cancer Institute
state: England
city: Hereford
country: United Kingdom
facility: Hereford Hospitals NHS Trust
state: England
city: High Wycombe
country: United Kingdom
facility: Wycombe General Hospital
state: England
city: Huddersfield, West Yorks
country: United Kingdom
facility: Huddersfield Royal Infirmary
state: England
city: Hull
country: United Kingdom
facility: Princess Royal Hospital at Hull and East Yorkshire NHS Trust
state: England
city: Ilford, Essex
country: United Kingdom
facility: King George Hospital
state: England
city: Ipswich
country: United Kingdom
facility: Ipswich Hospital
state: England
city: Isleworth
country: United Kingdom
facility: West Middlesex University Hospital
state: England
city: Keighley
country: United Kingdom
facility: Airedale General Hospital
state: England
city: Kettering, Northants
country: United Kingdom
facility: Kettering General Hosptial
state: England
city: Kidderminster Worcestershire
country: United Kingdom
facility: Kidderminster Hospital
state: England
city: King's Lynn
country: United Kingdom
facility: Queen Elizabeth Hospital
state: England
city: Lancanshire
country: United Kingdom
facility: Royal Albert Edward Infirmary
state: England
city: Lancaster
country: United Kingdom
facility: Royal Lancaster Infirmary
state: England
city: Leeds
country: United Kingdom
facility: Cookridge Hospital
state: England
city: Leeds
country: United Kingdom
facility: National Cancer Research Network
state: England
city: Leeds
country: United Kingdom
facility: Cancer Research UK Clinical Centre at St. James's University Hospital
state: England
city: Leeds
country: United Kingdom
facility: Leeds Cancer Centre at St. James's University Hospital
state: England
city: Liverpool
country: United Kingdom
facility: Royal Liverpool University Hospital
state: England
city: Liverpool
country: United Kingdom
facility: Aintree University Hospital
state: England
city: London
country: United Kingdom
facility: Barts and the London School of Medicine
state: England
city: London
country: United Kingdom
facility: Whittington Hospital
state: England
city: London
country: United Kingdom
facility: University College Hospital
state: England
city: London
country: United Kingdom
facility: Guy's Hospital
state: England
city: London
country: United Kingdom
facility: King's College Hospital
state: England
city: London
country: United Kingdom
facility: St. George's Hospital
state: England
city: London
country: United Kingdom
facility: St. Mary's Hospital
state: England
city: London
country: United Kingdom
facility: Charing Cross Hospital
state: England
city: Macclesfield
country: United Kingdom
facility: Macclesfield District General Hospital
state: England
city: Maidstone
country: United Kingdom
facility: Maidstone Hospital
state: England
city: Manchester
country: United Kingdom
facility: Christie Hospital
state: England
city: Manchester
country: United Kingdom
facility: Withington Hospital
state: England
city: Manchester
country: United Kingdom
facility: North Manchester General Hospital - Penine Actute Hospitals Trust
state: England
city: Margate
country: United Kingdom
facility: Queen Elizabeth The Queen Mother Hospital
state: England
city: Merseyside
country: United Kingdom
facility: Clatterbridge Centre for Oncology
state: England
city: Middlesbrough
country: United Kingdom
facility: James Cook University Hospital
state: England
city: Newcastle-Upon-Tyne
country: United Kingdom
facility: Northern Centre for Cancer Treatment at Newcastle General Hospital
state: England
city: Newport
country: United Kingdom
facility: St. Mary's Hospital
state: England
city: Norfolk
country: United Kingdom
facility: James Paget Hospital
state: England
city: North Shields
country: United Kingdom
facility: North Tyneside Hospital
state: England
city: North Yorkshire
country: United Kingdom
facility: Friarage Hospital
state: England
city: Northampton
country: United Kingdom
facility: Northampton General Hospital NHS Trust
state: England
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospital
state: England
city: Nottinghamshire
country: United Kingdom
facility: King's Mills Hospital
state: England
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital NHS Trust
state: England
city: Nuneaton
country: United Kingdom
facility: George Eliot Hospital
state: England
city: Oldham
country: United Kingdom
facility: Royal Oldham Hospital
state: England
city: Oxford
country: United Kingdom
facility: Radcliffe Infirmary NHS Trust
state: England
city: Oxford
country: United Kingdom
facility: Churchill Hospital
state: England
city: Peterborough
country: United Kingdom
facility: Peterborough Hospitals Trust
state: England
city: Pontefract West Yorkshire
country: United Kingdom
facility: Pontefract General Infirmary
state: England
city: Prescot Merseyside
country: United Kingdom
facility: Whiston Hospital
state: England
city: Preston
country: United Kingdom
facility: Royal Preston 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: Saint Leonards-on-Sea
country: United Kingdom
facility: Conquest 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: Solihull
country: United Kingdom
facility: Solihull Hospital
state: England
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
state: England
city: Southport
country: United Kingdom
facility: Southport and Formby District General Hospital
state: England
city: Stockport
country: United Kingdom
facility: Stepping Hill Hospital
state: England
city: Stoke-On-Trent
country: United Kingdom
facility: University Hospital of North Staffordshire
state: England
city: Sunderland
country: United Kingdom
facility: Sunderland Royal Hospital
state: England
city: Swindon
country: United Kingdom
facility: Great Western Hospital
state: England
city: Taunton
country: United Kingdom
facility: Taunton and Somerset Hospital
state: England
city: Torquay
country: United Kingdom
facility: Torbay Hospital
state: England
city: Truro, Cornwall
country: United Kingdom
facility: Royal Cornwall Hospital
state: England
city: Walsall
country: United Kingdom
facility: Walsall Manor Hospital
state: England
city: Warrington
country: United Kingdom
facility: Warrington Hospital NHS Trust
state: England
city: Warwick, Warwickshire
country: United Kingdom
facility: South Warwickshire Hospital
state: England
city: West Bromwich
country: United Kingdom
facility: Sandwell General Hospital
state: England
city: Westcliff-On-Sea
country: United Kingdom
facility: Southend University Hospital NHS Foundation Trust
state: England
city: Weston-super-Mare
country: United Kingdom
facility: Weston General Hospital
state: England
city: Winchester
country: United Kingdom
facility: Royal Hampshire County Hospital
state: England
city: Wolverhampton
country: United Kingdom
facility: New Cross Hospital
state: England
city: Worcester
country: United Kingdom
facility: Worcester Royal Hospital
state: England
city: Yeovil - Somerset
country: United Kingdom
facility: Yeovil District Hospital
state: England
city: Belfast
country: United Kingdom
facility: Belfast City Hospital Trust Incorporating Belvoir Park Hospital
state: Northern Ireland
city: Belfast
country: United Kingdom
facility: Centre for Cancer Research and Cell Biology at Queen's University Belfast
state: Northern Ireland
city: Londonderry
country: United Kingdom
facility: Altnagelvin Area Hospital
state: Northern Ireland
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
state: Scotland
city: Ayr
country: United Kingdom
facility: Ayr Hospital
state: Scotland
city: Dumfries
country: United Kingdom
facility: Dumfries & Galloway Royal Infirmary
state: Scotland
city: Dundee
country: United Kingdom
facility: Ninewells Hospital
state: Scotland
city: Dunfermline
country: United Kingdom
facility: Queen Margaret Hospital - Dunfermline
state: Scotland
city: East Kilbride
country: United Kingdom
facility: Hairmyres Hospital
state: Scotland
city: Edinburgh
country: United Kingdom
facility: Edinburgh Cancer Centre at Western General Hospital
state: Scotland
city: Elgin
country: United Kingdom
facility: Dr Gray's Hospital
state: Scotland
city: Falkirk
country: United Kingdom
facility: Falkirk & District Royal Infirmary
state: Scotland
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
state: Scotland
city: Glasgow
country: United Kingdom
facility: Royal Infirmary - Castle
state: Scotland
city: Greenock
country: United Kingdom
facility: Inverclyde Royal Hospital
state: Scotland
city: Inverness
country: United Kingdom
facility: Raigmore Hospital
state: Scotland
city: Kilmarnock
country: United Kingdom
facility: Crosshouse Hospital
state: Scotland
city: Livingston
country: United Kingdom
facility: St. John's Hospital
state: Scotland
city: Scarborough
country: United Kingdom
facility: Scarborough General Hospital
state: Scotland
city: Wakefield
country: United Kingdom
facility: Pinderfields General Hospital
state: Scotland
city: Wishaw
country: United Kingdom
facility: Wishaw General Hospital
state: Scotland
city: Aberystwyth
country: United Kingdom
facility: Bronglais District General Hospital
state: Wales
city: Bangor
country: United Kingdom
facility: Ysbyty Gwynedd
state: Wales
city: Bridgend
country: United Kingdom
facility: Princess of Wales Hospital
state: Wales
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Center at Velindre Hospital
state: Wales
city: Haverfordwest
country: United Kingdom
facility: Withybush General Hospital
state: Wales
city: Lhantrisant
country: United Kingdom
facility: Royal Glamorgan Hospital
state: Wales
city: Mid Glamorgan
country: United Kingdom
facility: Prince Charles Hospital
state: Wales
city: Newport Gwent
country: United Kingdom
facility: Royal Gwent Hospital
state: Wales
city: Rhyl, Denbighshire
country: United Kingdom
facility: Glan Clwyd Hospital
state: Wales
city: Wrexham
country: United Kingdom
facility: Wrexham Maelor Hospital
state: Wales
city: Barnet, Hertfordshire
country: United Kingdom
facility: Barnet General Hospital
Study officials:
affiliation: National Cancer Research Network
name: David Cameron, MD
role: STUDY_CHAIR
References:
citation: Hoon SN, Lau PK, White AM, Bulsara MK, Banks PD, Redfern AD. Capecitabine for hormone receptor-positive versus hormone receptor-negative breast cancer. Cochrane Database Syst Rev. 2021 May 26;5(5):CD011220. doi: 10.1002/14651858.CD011220.pub2.
citation: Cameron D, Morden JP, Canney P, Velikova G, Coleman R, Bartlett J, Agrawal R, Banerji J, Bertelli G, Bloomfield D, Brunt AM, Earl H, Ellis P, Gaunt C, Gillman A, Hearfield N, Laing R, Murray N, Couper N, Stein RC, Verrill M, Wardley A, Barrett-Lee P, Bliss JM; TACT2 Investigators. Accelerated versus standard epirubicin followed by cyclophosphamide, methotrexate, and fluorouracil or capecitabine as adjuvant therapy for breast cancer in the randomised UK TACT2 trial (CRUK/05/19): a multicentre, phase 3, open-label, randomised, controlled trial. Lancet Oncol. 2017 Jul;18(7):929-945. doi: 10.1016/S1470-2045(17)30404-7. Epub 2017 Jun 7.