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
ClinicalTrials.gov (NCT) NCT00070278
Clinical Trials Information System (CTIS) 2004-002356-34
Protocol serial number N0544160589
Sponsor Cambridge University Hospitals NHS Foundation Trust (UK)
Funders Cancer Research UK (CRUK) (UK), Eli Lilly & Company Limited (UK), Bristol Myers-Squibb (UK)
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

http://cancerhelp.cancerresearchuk.org/trials/a-trial-looking-at-chemotherapy-before-surgery-for-breast-cancer

Contact information

Dr Helena Earl
Scientific

Department of Oncology
Box 193
Addenbrooke's Hospital
Hills Road
Cambridge
CB2 2TT
United Kingdom

Study information

Primary study designInterventional
Study designMulticentre randomised controlled trial
Secondary study designRandomised controlled trial
Study type Participant information sheet
Scientific titleNeoadjuvant 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 acronymNeo-tAnGo
Study objectivesAdded 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) studiedEarly breast cancer
InterventionCurrent 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 typeOther
Primary outcome measure(s)

Added 12/08/09:
Complete pathological response after 4 courses

Key secondary outcome measure(s)

Added 12/08/09:
1. Overall survival
2. Disease-free survival
3. Effect of prognostic factors

Completion date31/05/2005

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexFemale
Target sample size at registration800
Key inclusion criteria1. 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 criteria1. 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 enrolment01/04/2000
Date of final enrolment31/05/2005

Locations

Countries of recruitment

  • United Kingdom
  • England

Study participating centre

Department of Oncology
Cambridge
CB2 2TT
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to shareNo
IPD sharing plan summary
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article sub-study results 19/08/2008 Yes No
Results article results 01/02/2014 Yes No
Participant information sheet Participant information sheet 11/11/2025 11/11/2025 No Yes
Plain English results No Yes

Editorial Notes

19/10/2018: Cancer Research UK lay results summary link added to Results (plain English)

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