Combination Chemotherapy in Treating Patients With Early Stage Breast Cancer That Has Been Removed By Surgery

Breast Cancer Clinical Trial

— TACT2  

Official title:

Trial of Accelerated Adjuvant Chemotherapy With Capecitabine in Early Breast Cancer (TACT2)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00301925
• Other study ID #: CDR0000463447
• Secondary ID: ICR-TACT2EU-2051
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 16, 2005
• Est. completion date: September 2024

Study information

• Verified date: August 2018
• Source: Institute of Cancer Research, United Kingdom
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 4400
• Est. completion date: September 2024
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Biological:
• pegfilgrastim

Drug:
• capecitabine

• cyclophosphamide

• epirubicin hydrochloride

• fluorouracil

• methotrexate

Procedure:
• adjuvant therapy

Locations

Country	Name	City	State
United Kingdom	Aberdeen Royal Infirmary	Aberdeen	Scotland
United Kingdom	Bronglais District General Hospital	Aberystwyth	Wales
United Kingdom	William Harvey Hospital	Ashford-Kent	England
United Kingdom	Wansbeck General Hospital	Ashington	England
United Kingdom	Tameside General Hospital	Ashton-Under-Lyne	England
United Kingdom	Ayr Hospital	Ayr	Scotland
United Kingdom	Ysbyty Gwynedd	Bangor	Wales
United Kingdom	Barnet General Hospital	Barnet, Hertfordshire
United Kingdom	North Devon District Hospital	Barnstaple	England
United Kingdom	Furness General Hospital	Barrow in Furness	England
United Kingdom	Basildon University Hospital	Basildon	England
United Kingdom	Basingstoke and North Hampshire NHS Foundation Trust	Basingstoke	England
United Kingdom	Belfast City Hospital Trust Incorporating Belvoir Park Hospital	Belfast	Northern Ireland
United Kingdom	Centre for Cancer Research and Cell Biology at Queen's University Belfast	Belfast	Northern Ireland
United Kingdom	Birmingham Heartlands Hospital	Birmingham	England
United Kingdom	City Hospital - Birmingham	Birmingham	England
United Kingdom	Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust	Birmingham	England
United Kingdom	Royal Blackburn Hospital	Blackburn	England
United Kingdom	Blackpool Victoria Hospital	Blackpool	England
United Kingdom	Royal Bolton Hospital	Bolton, Lancashire	England
United Kingdom	Bradford Royal Infirmary	Bradford	England
United Kingdom	Princess of Wales Hospital	Bridgend	Wales
United Kingdom	Sussex Cancer Centre at Royal Sussex County Hospital	Brighton	England
United Kingdom	Bristol Haematology and Oncology Centre	Bristol	England
United Kingdom	Broomfield Hospital	Broomefield	England
United Kingdom	Burnley General Hospital	Burnley	England
United Kingdom	Queen's Hospital	Burton-upon-Trent	England
United Kingdom	West Suffolk Hospital	Bury St. Edmunds	England
United Kingdom	Addenbrooke's Hospital	Cambridge	England
United Kingdom	Kent and Canterbury Hospital	Canterbury	England
United Kingdom	Velindre Cancer Center at Velindre Hospital	Cardiff	Wales
United Kingdom	Cheltenham General Hospital	Cheltenham	England
United Kingdom	Halton Hospital	Cheshire	England
United Kingdom	Chesterfield Royal Hospital	Chesterfield	England
United Kingdom	Saint Richards Hospital	Chichester	England
United Kingdom	Essex County Hospital	Colchester	England
United Kingdom	Walsgrave Hospital	Coventry	England
United Kingdom	Darent Valley Hospital	Dartford Kent	England
United Kingdom	Derbyshire Royal Infirmary	Derby	England
United Kingdom	Dewsbury and District Hospital	Dewsbury	England
United Kingdom	Doncaster Royal Infirmary	Doncaster	England
United Kingdom	Russells Hall Hospital	Dudley	England
United Kingdom	Dumfries & Galloway Royal Infirmary	Dumfries	Scotland
United Kingdom	Ninewells Hospital	Dundee	Scotland
United Kingdom	Queen Margaret Hospital - Dunfermline	Dunfermline	Scotland
United Kingdom	University Hospital of North Durham	Durham	England
United Kingdom	Hairmyres Hospital	East Kilbride	Scotland
United Kingdom	Eastbourne District General Hospital	Eastbourne	England
United Kingdom	Edinburgh Cancer Centre at Western General Hospital	Edinburgh	Scotland
United Kingdom	Dr Gray's Hospital	Elgin	Scotland
United Kingdom	Royal Devon and Exeter Hospital	Exeter	England
United Kingdom	Falkirk & District Royal Infirmary	Falkirk	Scotland
United Kingdom	Queen Elizabeth Hospital	Gateshead	England
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow	Scotland
United Kingdom	Royal Infirmary - Castle	Glasgow	Scotland
United Kingdom	Gloucestershire Royal Hospital	Gloucester	England
United Kingdom	Inverclyde Royal Hospital	Greenock	Scotland
United Kingdom	Diana Princess of Wales Hospital	Grimsby	England
United Kingdom	St. Luke's Cancer Centre at Royal Surrey County Hospital	Guildford	England
United Kingdom	UCL Cancer Institute	Hampstead, London	England
United Kingdom	Withybush General Hospital	Haverfordwest	Wales
United Kingdom	Hereford Hospitals NHS Trust	Hereford	England
United Kingdom	Wycombe General Hospital	High Wycombe	England
United Kingdom	Huddersfield Royal Infirmary	Huddersfield, West Yorks	England
United Kingdom	Princess Royal Hospital at Hull and East Yorkshire NHS Trust	Hull	England
United Kingdom	King George Hospital	Ilford, Essex	England
United Kingdom	Raigmore Hospital	Inverness	Scotland
United Kingdom	Ipswich Hospital	Ipswich	England
United Kingdom	West Middlesex University Hospital	Isleworth	England
United Kingdom	Airedale General Hospital	Keighley	England
United Kingdom	Kettering General Hosptial	Kettering, Northants	England
United Kingdom	Kidderminster Hospital	Kidderminster Worcestershire	England
United Kingdom	Crosshouse Hospital	Kilmarnock	Scotland
United Kingdom	Queen Elizabeth Hospital	King's Lynn	England
United Kingdom	Royal Albert Edward Infirmary	Lancanshire	England
United Kingdom	Royal Lancaster Infirmary	Lancaster	England
United Kingdom	Cancer Research UK Clinical Centre at St. James's University Hospital	Leeds	England
United Kingdom	Cookridge Hospital	Leeds	England
United Kingdom	Leeds Cancer Centre at St. James's University Hospital	Leeds	England
United Kingdom	National Cancer Research Network	Leeds	England
United Kingdom	Royal Glamorgan Hospital	Lhantrisant	Wales
United Kingdom	Aintree University Hospital	Liverpool	England
United Kingdom	Royal Liverpool University Hospital	Liverpool	England
United Kingdom	St. John's Hospital	Livingston	Scotland
United Kingdom	Barts and the London School of Medicine	London	England
United Kingdom	Charing Cross Hospital	London	England
United Kingdom	Guy's Hospital	London	England
United Kingdom	King's College Hospital	London	England
United Kingdom	St. George's Hospital	London	England
United Kingdom	St. Mary's Hospital	London	England
United Kingdom	University College Hospital	London	England
United Kingdom	Whittington Hospital	London	England
United Kingdom	Altnagelvin Area Hospital	Londonderry	Northern Ireland
United Kingdom	Macclesfield District General Hospital	Macclesfield	England
United Kingdom	Maidstone Hospital	Maidstone	England
United Kingdom	Christie Hospital	Manchester	England
United Kingdom	North Manchester General Hospital - Penine Actute Hospitals Trust	Manchester	England
United Kingdom	Withington Hospital	Manchester	England
United Kingdom	Queen Elizabeth The Queen Mother Hospital	Margate	England
United Kingdom	Clatterbridge Centre for Oncology	Merseyside	England
United Kingdom	Prince Charles Hospital	Mid Glamorgan	Wales
United Kingdom	James Cook University Hospital	Middlesbrough	England
United Kingdom	Northern Centre for Cancer Treatment at Newcastle General Hospital	Newcastle-Upon-Tyne	England
United Kingdom	St. Mary's Hospital	Newport	England
United Kingdom	Royal Gwent Hospital	Newport Gwent	Wales
United Kingdom	James Paget Hospital	Norfolk	England
United Kingdom	North Tyneside Hospital	North Shields	England
United Kingdom	Friarage Hospital	North Yorkshire	England
United Kingdom	Northampton General Hospital NHS Trust	Northampton	England
United Kingdom	Norfolk and Norwich University Hospital	Norwich	England
United Kingdom	Nottingham City Hospital NHS Trust	Nottingham	England
United Kingdom	King's Mills Hospital	Nottinghamshire	England
United Kingdom	George Eliot Hospital	Nuneaton	England
United Kingdom	Royal Oldham Hospital	Oldham	England
United Kingdom	Churchill Hospital	Oxford	England
United Kingdom	Radcliffe Infirmary NHS Trust	Oxford	England
United Kingdom	Peterborough Hospitals Trust	Peterborough	England
United Kingdom	Pontefract General Infirmary	Pontefract West Yorkshire	England
United Kingdom	Whiston Hospital	Prescot Merseyside	England
United Kingdom	Royal Preston Hospital	Preston	England
United Kingdom	Alexandra Healthcare NHS	Redditch, Worcestershire	England
United Kingdom	Glan Clwyd Hospital	Rhyl, Denbighshire	Wales
United Kingdom	Oldchurch Hospital	Romford	England
United Kingdom	Conquest Hospital	Saint Leonards-on-Sea	England
United Kingdom	Salisbury District Hospital	Salisbury	England
United Kingdom	Scarborough General Hospital	Scarborough	Scotland
United Kingdom	Scunthorpe General Hospital	Scunthorpe	England
United Kingdom	Cancer Research Centre at Weston Park Hospital	Sheffield	England
United Kingdom	Royal Shrewsbury Hospital	Shrewsbury	England
United Kingdom	Solihull Hospital	Solihull	England
United Kingdom	Southampton General Hospital	Southampton	England
United Kingdom	Southport and Formby District General Hospital	Southport	England
United Kingdom	Stepping Hill Hospital	Stockport	England
United Kingdom	University Hospital of North Staffordshire	Stoke-On-Trent	England
United Kingdom	Sunderland Royal Hospital	Sunderland	England
United Kingdom	Great Western Hospital	Swindon	England
United Kingdom	Taunton and Somerset Hospital	Taunton	England
United Kingdom	Torbay Hospital	Torquay	England
United Kingdom	Royal Cornwall Hospital	Truro, Cornwall	England
United Kingdom	Pinderfields General Hospital	Wakefield	Scotland
United Kingdom	Walsall Manor Hospital	Walsall	England
United Kingdom	Warrington Hospital NHS Trust	Warrington	England
United Kingdom	South Warwickshire Hospital	Warwick, Warwickshire	England
United Kingdom	Sandwell General Hospital	West Bromwich	England
United Kingdom	Southend University Hospital NHS Foundation Trust	Westcliff-On-Sea	England
United Kingdom	Weston General Hospital	Weston-super-Mare	England
United Kingdom	Royal Hampshire County Hospital	Winchester	England
United Kingdom	Wishaw General Hospital	Wishaw	Scotland
United Kingdom	New Cross Hospital	Wolverhampton	England
United Kingdom	Worcester Royal Hospital	Worcester	England
United Kingdom	Wrexham Maelor Hospital	Wrexham	Wales
United Kingdom	Yeovil District Hospital	Yeovil - Somerset	England

Sponsors (1)

Lead Sponsor	Collaborator
Institute of Cancer Research, United Kingdom

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-free survival (DFS) at 5 years
Secondary	Overall survival at 5 years
Secondary	Distant DFS at 5 years
Secondary	Tolerability (including serious adverse events, dose-intensity, and toxicity)
Secondary	Detailed toxicity
Secondary	Quality of life