Combination Chemotherapy in Treating Women With Resected Breast Cancer

Sponsor

Institute of Cancer Research, United Kingdom (Other)

Overall Status

Unknown status

CT.gov ID

NCT00033683

Collaborator

(none)

Locations

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: CMF regimen Drug: cyclophosphamide Drug: docetaxel Drug: epirubicin hydrochloride Drug: fluorouracil Drug: methotrexate Drug: tamoxifen citrate Procedure: adjuvant therapy Radiation: radiation therapy	Phase 2

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 Design

Study Type:

Interventional

Allocation:

Randomized

Primary Purpose:

Treatment

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 Start Date :

Feb 1, 2001

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

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