Condition category
Cancer
Date applied
25/11/2004
Date assigned
20/12/2004
Last edited
07/01/2014
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Dr Helena Earl

ORCID ID

Contact details

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

Additional identifiers

EudraCT number

2004-002356-34

ClinicalTrials.gov number

NCT00070278

Protocol/serial number

N0544160589

Study information

Scientific title

Acronym

Neo-tAnGo

Study hypothesis

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

Not provided at time of registration

Study design

Multicentre randomised controlled 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 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

Phase

Phase III

Drug names

Primary outcome measures

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 trial start date

01/04/2000

Overall trial end date

31/05/2005

Reason abandoned

Eligibility

Participant 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

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

800

Participant 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

Recruitment start date

01/04/2000

Recruitment end date

31/05/2005

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Department of Oncology
Cambridge
CB2 2TT
United Kingdom

Sponsor information

Organisation

Cambridge University Hospitals NHS Foundation Trust (UK)

Sponsor details

Addenbrooke's NHS Trust R&D Office
Addenbrooke's Hospital
Cambridge
CB2 2TT
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Charity

Funder name

Cancer Research UK (CRUK) (UK)

Alternative name(s)

CRUK

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Funder name

Eli Lilly & Company Limited (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Bristol Myers-Squibb (UK)

Alternative name(s)

Bristol-Myers Squibb Company, BMS

Funding Body Type

private sector organisation

Funding Body Subtype

corporate

Location

United States of America

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

2008 sub-study results in: http://www.ncbi.nlm.nih.gov/pubmed/18665163
2013 results in: http://www.ncbi.nlm.nih.gov/pubmed/24360787

Publication citations

  1. Results

    Earl HM, Vallier AL, Hiller L, Fenwick N, Young J, Iddawela M, Abraham J, Hughes-Davies L, Gounaris I, McAdam K, Houston S, Hickish T, Skene A, Chan S, Dean S, Ritchie D, Laing R, Harries M, Gallagher C, Wishart G, Dunn J, Provenzano E, Caldas C, , Effects of the addition of gemcitabine, and paclitaxel-first sequencing, in neoadjuvant sequential epirubicin, cyclophosphamide, and paclitaxel for women with high-risk early breast cancer (Neo-tAnGo): an open-label, 2×2 factorial randomised phase 3 trial., Lancet Oncol., 2014, 15, 2, 201-212, doi: 10.1016/S1470-2045(13)70554-0.

  2. Wardley AM, Hiller L, Howard HC, Dunn JA, Bowman A, Coleman RE, Fernando IN, Ritchie DM, Earl HM, Poole CJ, , tAnGo: a randomised phase III trial of gemcitabine in paclitaxel-containing, epirubicin/cyclophosphamide-based, adjuvant chemotherapy for early breast cancer: a prospective pulmonary, cardiac and hepatic function evaluation., Br. J. Cancer, 2008, 99, 4, 597-603, doi: 10.1038/sj.bjc.6604538.

Additional files

Editorial Notes