Condition category
Cancer
Date applied
23/02/2009
Date assigned
19/03/2009
Last edited
13/12/2011
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Contact information

Type

Scientific

Primary contact

Prof Nigel Bundred

ORCID ID

Contact details

University of Manchester
c/o University of South Manchester NHS Foundation Trust
2nd Floor
Education and Research Centre
Southmoor Road
Manchester
M23 9LT
United Kingdom
bundred@manchester.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

NCT01104571

Protocol/serial number

ICR-CTSU/2008/10017

Study information

Scientific title

Effect of peri-operative anti-HER2 therapy on early breast cancer: a randomised phase III open-label multicentre clinical trial

Acronym

EPHOS-B

Study hypothesis

The EPHOS-B study will test the hypothesis that peri-operative anti-HER2 therapy causes a significant increase in tumour apoptosis and a significant decrease in tumour cell proliferation.

Please note that as of 19/02/10 this record has been updated. All updates can be found in the relevant field with the above update date. Please also note that the start and end dates of this trial have been updated from 01/06/2009 and 01/12/2009 to 01/04/2010 and 01/11/2021 respectively. This includes the follow up period.

Ethics approval

West Midlands Research Ethics Committee on 12/01/2010 (ref: 09/H1208/52)

Study design

Randomised phase III open-label multicentre clinical trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Early breast cancer

Intervention

Current information as of 19/02/10:
Group I: control (i.e. no peri-operative treatment)
Group II: trastuzumab 6 mg/kg intravenous (iv) given on days 1 and 8 pre-surgery, and 2 mg/kg iv on day 15 post-operatively
Group III: Lapatinib 1500mg/day p.o. continuously for 28 days, starting 11 days (± 1 day) pre-surgery.

Initial information at time of registration:
Group I: control (i.e. no peri-operative treatment)
Group II: trastuzumab 6 mg/kg intravenous (iv) given on days 1 and 8 pre-surgery, and 2 mg/kg iv on days 15 and 22 post-operatively
Group III: lapatinib 1500 mg/day orally (p.o.) for approximately 6 weeks, starting 11 days (± 1 day) pre-operatively and continued for 4 weeks post-operatively

Patients should be followed-up 28 days after surgery and then every 6 months until the end of year 2. Patients will then be followed up annually for at least 10 years after completion of recruitment.

Joint sponsors:
University Hospital of South Manchester NHS Foundation Trust (UK)
2nd Floor, Education and Research Centre
Southmoor Road
Manchester M23 9LT
United Kingdom
Email: Bundred@manchester.ac.uk
http://www.uhsm.nhs.uk/Pages/Home.aspx

Institute of Cancer Research (ICR) (UK)
123 Old Brompton Road
London SW7 3PR
Tel: +44 (0)20 8722 4188
Fax: +44 (0)20 8770 7876
Email: Barbara.Pittam@icr.ac.uk
http://www.icr.ac.uk

Intervention type

Drug

Phase

Phase III

Drug names

Trastuzumab, lapatinib

Primary outcome measures

1. Increase in apoptosis: change in the tumour (morphological apoptosis and activated caspase 3) measured at diagnosis and at surgery
2. Fall in proliferation between diagnosis and surgery: change in proliferation measured by Ki67 immunohistochemical assessment (%) at diagnosis and at surgery

Secondary outcome measures

1. Changes in the angiogenic serum markers vascular endothelial growth factor A (VEGF-A), VEGF-R1 and CD105, measured at diagnosis, surgery (plus also tumour CD31) and 28 days post-surgery
2. To establish if the expression of molecular markers (epidermal growth factor receptor [EGFR], Her-3, insulin-like growth factor 1 receptor [IGF1R], c-myc, Akt, p-ERK, pS6 Kinase, activated Src, or truncated p95HER-2 expression) predict increases in apoptosis or decreases in proliferation in response to therapy

Overall trial start date

01/04/2010

Overall trial end date

01/11/2021

Reason abandoned

Eligibility

Participant inclusion criteria

1. Women aged greater than or equal to 18 years old
2. HER2 (3+ on immunohistochemistry [IHC] or amplification proven by fluorescent in-situ hybridisation [FISH]) positive operable invasive breast cancer diagnosed by core biopsy
3. Planned surgery within one month of diagnosis
4. Serum creatinine and bilirubin less than 2 times the upper limits of normal for the institution, or creatinine clearance greater than 30 mg/dL (Marginally
abnormal test results should be repeated)
5. Eastern Cooperative Oncology Group (ECOG) performance status 0,1, or 2 (Karnofsky greater than or equal to 60%)
6. Non-pregnant and non-lactating with no intention of pregnancy during study treatment
7. Written informed consent obtained for trial and to donation of tissue and blood samples

Added 19/02/10:
8. Patients must be candidates for and willing to undergo adjuvant chemotherapy and trastuzumab post surgery

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

250

Participant exclusion criteria

Current information as of 19/02/10:
1. HER2 negative cancers and those with unknown HER2 status
2. Inoperable breast cancer (T4 category) or suspicion of distant metastases
3. Diagnosis of inflammatory breast cancer
4. Clinical evidence of metastatic disease
5. Prior herceptin therapy within the last 3 months or local (radiotherapy) cancer treatments
6. Previous cancer at any other site that has been treated within the last 6 months (except previous basal cell carcinoma and cervical carcinoma in situ)
7. Have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
8. Impaired gastro-intestinal function thought sufficient to reduce lapatinib absorption
9. Contra-indicated to receive adjuvant chemotherapy and/or trastuzumab (ECOG >2)
10. Known immediate or delayed hypersensitivity, reaction to drugs chemically related to trastuzumab or lapatinib
11. Other concomitant investigational agents or concurrent anti-cancer therapy
12. Regular use of systemic steroids or other agents that could influence study endpoints (inhaled steroids are allowed)
13. Any altered mental state that would preclude obtaining written informed consent
14. Patients who have clinically significant cardiac abnormalities or uncontrolled hypertension
15. Previous myocardial infarction, heart failure, or significant angina. Cardiac function should be assessed by physical examination, ECG, and baseline LVEF should be ≥55% as measured by echocardiography or MUGA.

Initial information at time of registration:
1. HER2 negative cancers and those with unknown HER2 status
2. Inoperable breast cancer (T4 category) or suspicion of distant metastases
3. Diagnosis of inflammatory breast cancer
4. Clinical evidence of metastatic disease
5. No prior systemic (i.e. chemotherapy) or local (radiotherapy) cancer treatments
6. Previous cancer at any other site (except previous basal cell carcinoma and cervical carcinoma in situ)
7. Abnormal renal function
8. Abnormal liver function tests
9. Have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
10. Impaired gastro-intestinal function thought sufficient to reduce lapatinib absorption
11. Contra-indication to receive adjuvant chemotherapy and/or trastuzumab (ECOG greater than 2)
12. Known immediate or delayed hypersensitivity, reaction to drugs chemically related to trastuzumab or lapatinib
13. Other concomitant investigational agents or concurrent anti-cancer therapy. In addition all herbal (alternative) therapies are prohibited.
14. Regular use of systemic steroids or other agents that could influence study endpoints
15. Patient must not have clinically significant cardiac abnormalities or uncontrolled hypertension
16. No previous myocardial infarction, heart failure, or significant angina. Cardiac function should be assessed by physical examination, electrocardiogram (ECG), and baseline left ventricular ejection fraction (LVEF) should be greater than or equal to 50% as measured by echocardiography or multiple-gated acquisition (MUGA) scan.

Recruitment start date

01/04/2010

Recruitment end date

01/11/2021

Locations

Countries of recruitment

United Kingdom

Trial participating centre

University of Manchester
Manchester
M23 9LT
United Kingdom

Sponsor information

Organisation

University of Manchester (UK)

Sponsor details

Oxford Road
Manchester
M13 9PL
United Kingdom

Sponsor type

University/education

Website

http://www.manchester.ac.uk

Funders

Funder type

Charity

Funder name

Cancer Research UK (CRUK) (UK) (ref: C7525/A8965)

Alternative name(s)

CRUK

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Funder name

GlaxoSmithKline (UK)

Alternative name(s)

GlaxoSmithKline Plc., GSK

Funding Body Type

private sector organisation

Funding Body Subtype

corporate

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes