Neoadjuvant study of sequential epirubicin/cyclophosphamide and paclitaxel ± gemcitabine in the treatment of high risk early breast cancer with molecular profiling, proteomics and candidate gene analysis
| ISRCTN | ISRCTN78234870 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN78234870 |
| EudraCT/CTIS number | 2004-002356-34 |
| ClinicalTrials.gov number | NCT00070278 |
| Secondary identifying numbers | N0544160589 |
- Submission date
- 25/11/2004
- Registration date
- 20/12/2004
- Last edited
- 19/10/2018
- 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
Dr Helena Earl
Scientific
Scientific
Department of Oncology
Box 193
Addenbrooke's Hospital
Hills Road
Cambridge
CB2 2TT
United Kingdom
Study information
| Study design | Multicentre randomised controlled 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 | Neoadjuvant study of sequential epirubicin/cyclophosphamide and paclitaxel ± gemcitabine in the treatment of high risk early breast cancer with molecular profiling, proteomics and candidate gene analysis |
| Study acronym | Neo-tAnGo |
| Study objectives | Added 12/08/09: Some women diagnosed with early breast cancer are advised to have chemotherapy before surgery (neoadjuvant chemotherapy). The aim of this neoadjuvant breast cancer study is to determine the benefit of adding gemcitabine (a newer anticancer chemotherapy drug) to epirubicin, cyclophosphamide and paclitaxel (standard chemotherapy treatment) in the neoadjuvant setting. As of 12/08/09 this record has been extensively updated. All updates can be found in the relevant field with the above update date. |
| Ethics approval(s) | Not provided at time of registration |
| Health condition(s) or problem(s) studied | Early breast cancer |
| Intervention | Current information as of 12/08/09: This is a randomised, multicenter study. Patients are stratified according to estrogen-receptor status (negative vs greater than 10% positive cells), HER-2 status (positive vs negative), tumor size (30-50 mm vs greater than 50 mm), and clinical involvement of axillary nodes (yes vs no). Patients are randomized to 1 of 4 treatment arms. 1. Neoadjuvant sequential chemotherapy: 1.1. Arm 1: Patients receive epirubicin IV and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Patients then receive paclitaxel IV over 3 hours on day one. Treatment repeats every 21 days for 4 courses. 1.2. Arm 2: Patients receive paclitaxel as in arm I followed by epirubicin and cyclophosphamide as in arm I. 1.3. Arm 3: Patients receive epirubicin and cyclophosphamide as in arm I followed by paclitaxel as in arm I and gemcitabine IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for 4 courses. 1.4 Arm 4: Patients receive paclitaxel as in arm I and gemcitabine as in arm III followed by epirubicin and cyclophosphamide as in arm I. 2. Surgery: After completion of neoadjuvant chemotherapy, patients in all arms undergo definitive surgery. 3. Radiotherapy: Radiotherapy will be given as appropriate 4. Tumor tissue is removed from a subset of patients during serial biopsies. Molecular and genetic profiling, mutation analysis, and comparative genomic analysis is performed on the tissue samples. 5. Quality of life is assessed at baseline, after 4 courses of chemotherapy, after the completion of chemotherapy, after surgery, and then every 6 months for 2 years. 6. Patients are followed every 2 months for 2 years and then every 3 months for 3 years. Initial information at time of registration: Phase III, multi-centre, prospective, randomised trial of neoadjuvant chemotherapy involving recruitment of 800 patient volunteers. All patients will receive four cycles of Epirubicin (E) (90 mg/m^2, every three weeks) and Cyclophosphamide (C) (600 mg/m^2, every three weeks) and either four cycles of paclitaxel (T) (175 mg/m^2, every two weeks) alone, or four cycles paclitaxel in combination with Gemcitabine (G) (2000 mg/m^2, day one and then every two weeks), according to randomisation. A further sub-randomisation will be conducted to assess the effect of treatment sequence (i.e. EC followed by T ± G versus T ± G followed by EC). |
| Intervention type | Other |
| Primary outcome measure | Added 12/08/09: Complete pathological response after 4 courses |
| Secondary outcome measures | Added 12/08/09: 1. Overall survival 2. Disease-free survival 3. Effect of prognostic factors |
| Overall study start date | 01/04/2000 |
| Completion date | 31/05/2005 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Female |
| Target number of participants | 800 |
| Key inclusion criteria | 1. Women with histological diagnosis of invasive breast cancer 2. T2 tumour or above (ultrasound size mroe than 20 mm) 3. Any hormone receptor status 4. Patient fit to receive any of the trial chemotherapy regimens 5. Patient must have adequate bone marrow, hepatic, renal, and cardiac function 6. Eastern Cooperative Oncology Group (ECOG) performance status of zero, one, or two 7. No previous chemotherapy or radiotherapy 8. No previous malignancy except basal cell carcinoma or cervical carcinoma in situ, unless disease-free for ten years, after surgical treatment only 9. Chemotherapy should start as soon as possible but must commence within four weeks of biopsy 10. Randomisation needs to take place within three weeks of biopsy 11. Non-pregnant and non-lactating 12. No concomitant medical or psychiatric problems that might prevent completion of treatment or follow-up 13. 18 years or older 14. Written informed consent for the study |
| Key exclusion criteria | 1. Previous treatment with irinotecan 2. Any condition requiring ongoing ciclosporin treatment 3. Ongoing treatment with cetuximab (NB previous cetuximab is not an exclusion criterion, provided it has stopped more than three weeks before randomisation) 4. If a female of child-bearing age, a positive pregnancy test, or not using adequate contraception 5. Concurrent or previous other cancer (excluding non-melanomatous skin cancer) 6. Known Central Nervous System (CNS) metastases, carcinomatous meningitis or recent history of seizures 7. Major thoracic or abdominal surgery within preceding four weeks 8. Chronic enteropathy (e.g. Crohn's disease, ulcerative colitis) 9. Chronic diarrhoea of any cause, whether or not related to the colorectal cancer or surgery 10. Unresolved bowel obstruction 11. Uncontrolled infection 12. Incapable of reliable oral self-medication 13. Any other condition, which, in the investigator's opinion would make the patient unsuitable for participation in the trial |
| Date of first enrolment | 01/04/2000 |
| Date of final enrolment | 31/05/2005 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Department of Oncology
Cambridge
CB2 2TT
United Kingdom
CB2 2TT
United Kingdom
Sponsor information
Cambridge University Hospitals NHS Foundation Trust (UK)
Hospital/treatment centre
Hospital/treatment centre
Addenbrooke's NHS Trust R&D Office
Addenbrooke's Hospital
Cambridge
CB2 2TT
England
United Kingdom
"ROR" |
https://ror.org/04v54gj93 |
|---|
Funders
Funder type
Charity
Cancer Research UK (CRUK) (UK)
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
Eli Lilly & Company Limited (UK)
No information available
Bristol Myers-Squibb (UK)
Government organisation / For-profit companies (industry)
Government organisation / For-profit companies (industry)
- Alternative name(s)
- Bristol-Myers Squibb Company, BMS
- Location
- United States of America
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Plain English results | No | Yes | |||
| Results article | sub-study results | 19/08/2008 | Yes | No | |
| Results article | results | 01/02/2014 | Yes | No |
Editorial Notes
19/10/2018: Cancer Research UK lay results summary link added to Results (plain English)
