Effect of Peri-operative anti-HER2 therapy On early breast cancer Study - Biological phase
| ISRCTN | ISRCTN15004993 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN15004993 |
| EudraCT/CTIS number | 2008-005466-30 |
| IRAS number | 6930 |
| ClinicalTrials.gov number | NCT01104571 |
| Secondary identifying numbers | ICR-CTSU/2008/10017, IRAS 6930 |
- Submission date
- 23/02/2009
- Registration date
- 19/03/2009
- Last edited
- 21/12/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Contact information
Prof Nigel Bundred
Scientific
Scientific
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 |
Ms Jane Banerji
Public
Public
ICR-CTSU
Sir Richard Doll Building
Institue of Cancer Research
Cotswold Road
Sutton
SM2 5NG
United Kingdom
| Phone | +44(0)0208 722 4349 |
|---|---|
| EPHOS-B-icrctsu@icr.ac.uk |
Study information
| Study design | Randomized phase III open-label multicentre clinical trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | Effect of peri-operative anti-HER2 therapy on early breast cancer: a randomised phase III open-label multicentre clinical trial |
| Study acronym | EPHOS-B |
| Study objectives | 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(s) |
Approved 12/01/2010, West Midlands Research Ethics Committee (1st Floor, NHSBT Newcastle Blood Donor Centre, Holland Drive, Newcastle Upon Tyne, NE2 4NQ, United Kingdom; +44 (0)2071048357; edgbaston.rec@hra.nhs.uk), ref: 09/H1208/52 |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | Trastuzumab, lapatinib |
| Primary outcome measure | 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 study start date | 01/04/2010 |
| Completion date | 19/12/2022 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Female |
| Target number of participants | 250 |
| Total final enrolment | 257 |
| Key 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 |
| Key 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. |
| Date of first enrolment | 01/04/2010 |
| Date of final enrolment | 30/09/2015 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
University of Manchester
Manchester
M23 9LT
United Kingdom
M23 9LT
United Kingdom
Sponsor information
University of Manchester (UK)
University/education
University/education
Oxford Road
Manchester
M13 9PL
England
United Kingdom
| Website | http://www.manchester.ac.uk |
|---|---|
"ROR" |
https://ror.org/027m9bs27 |
Funders
Funder type
Charity
Cancer Research UK (CRUK) (UK) (ref: C7525/A8965)
Private sector organisation / Other non-profit organizations
Private sector organisation / Other non-profit organizations
- Alternative name(s)
- CR_UK, Cancer Research UK - London, CRUK
- Location
- United Kingdom
GlaxoSmithKline (UK)
Government organisation / For-profit companies (industry)
Government organisation / For-profit companies (industry)
- Alternative name(s)
- GlaxoSmithKline plc., GSK plc., GSK
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 01/12/2019 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Has been presented at international conferences and published in Clinical Cancer Research April 2022 |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request. EPHOS-B-icrctsu@icr.ac.uk |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Abstract results | 01/03/2016 | 09/03/2023 | No | No | |
| Poster results | version 2 | 07/12/2021 | 09/03/2023 | No | No |
| Results article | 01/04/2022 | 09/03/2023 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No | ||
| Plain English results | 17/07/2023 | No | Yes | ||
| Protocol file | version 8.0 | 04/09/2019 | 21/12/2023 | No | No |
Additional files
Editorial Notes
21/12/2023: The following changes were made:
1. EudraCT/CTIS number added.
2. IRAS number added.
3. The study website was added.
4. Protocol file (not peer reviewed added).
17/07/2023: Results in plain English added to the study outputs table. Total final enrolment added.
09/03/2023: The following changes were made to the trial record:
1. The overall end date was changed from 01/11/2021 to 19/12/2022.
2. The participant level data sharing statement was added.
3. The publication and dissemination plan was added.
4. Publication reference, abstract, and poster added.
23/07/2019: The following changes were made to the trial record:
1. The recruitment end date was changed from 01/11/2021 to 30/09/2015.
2. The intention to publish date was added.
3. Jane Banerji was added as public contact.
