Triple Negative Trial: a randomised phase III trial of carboplatin compared to docetaxel for patients with advanced oestrogen receptor-progesterone receptor-human epidermal growth factor receptor two-breast cancer
| ISRCTN | ISRCTN97330959 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN97330959 |
| ClinicalTrials.gov (NCT) | NCT00532727 |
| Clinical Trials Information System (CTIS) | 2006-004470-26 |
| Protocol serial number | ICR-CTSU/2006/10003 |
| Sponsor | Institute of Cancer Research and King's College London (UK) |
| Funders | Cancer Research UK (UK), Breakthrough Breast Cancer (UK) |
- Submission date
- 26/01/2007
- Registration date
- 20/03/2007
- Last edited
- 18/02/2019
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Plain English summary of protocol
Contact information
Scientific
Guy's & St Thomas' Hospital NHS Foundation Trust
Breast Unit
St Thomas Street
London
SE1 9RT
United Kingdom
| Phone | +44 (0)20 7188 4237 |
|---|---|
| andrew.tutt@icr.ac.uk |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Phase III multicentre randomised trial |
| Secondary study design | Randomised controlled trial |
| Study type | Participant information sheet |
| Scientific title | Triple Negative Trial: a randomised phase III trial of carboplatin compared to docetaxel for patients with advanced oestrogen receptor-progesterone receptor-human epidermal growth factor receptor two-breast cancer |
| Study acronym | TNT |
| Study objectives | To determine whether there is greater activity for carboplatin than a taxane standard of care (docetaxel) in women with oEstrogen Receptor-Progesterone Receptor-Human Epidermal growth factor Receptor 2 (ER-PR-HER2) breast cancer. The trial aims to recruit between 350 and 450 patients. |
| Ethics approval(s) | East London and the City Research Ethics Committee 1, 11/06/2007 |
| Health condition(s) or problem(s) studied | Metastatic or recurrent locally advanced disease |
| Intervention | Arm A: Carboplatin area under the concentration–time curve (AUC) six, every three weeks for six cycles (18 weeks) Arm B: Docetaxel 100 mg/m^2, every three weeks for six cycles (18 weeks) Cross over to alternative treatment on progression. |
| Intervention type | Drug |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | Carboplatin, docetaxel |
| Primary outcome measure(s) |
Response will be evaluated after three and six cycles of chemotherapy using modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria, with appropriate clinical assessment and radiological investigations. |
| Key secondary outcome measure(s) |
1. Time to progression: this will be defined according to RECIST criteria and will be measured from the start of treatment until the confirmation of progression |
| Completion date | 31/03/2020 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Female |
| Target sample size at registration | 400 |
| Key inclusion criteria | 1. Histologically confirmed ER-, PR-, primary breast cancer (Allred less than three or H score less than ten or ER- and PR- negative, if other cut-offs used [e.g., 1%, 5% or 10%]) 2. Histologically confirmed HER2- primary breast cancer (ImmunoHistoChemistry [IHC] scoring 0 or 1+ for HER2 or non-amplified for HER2 [Fluorescence In Situ Hybridisation {FISH}]) 3. Measurable confirmed metastatic or recurrent locally advanced disease unsuitable for local therapy 4. Patients with stable, treated brain metastases will be eligible providing informed consent can be given and that other sites of measurable disease are present 5. Eastern Cooperative Oncology Group (ECOG) performance status zero, one or two 6. Adequate haematology, biochemical indices (Full Blood Count [FBC], Urea and Electrolytes [U & Es]) 7. Liver Function Tests (LFTs): normal bilirubin, Aspartate Aminotransferase (AST) and/or Alanine Aminotransferase (ALT) less than or equal to 3 x Upper Limit of Normal (ULN) if Alkaline Phosphatase is greater than 5 x ULN (or an isolated elevation AST/ALT of less than or equal to 5 x ULN) 8. Adequate renal function 9. Written informed consent, able to comply with treatment and follow-up |
| Key exclusion criteria | 1. Original primary tumour or subsequent relapse known to be positive for any of ER, PR, or HER2 receptors 2. Patients with inoperable locally advanced disease suitable for local radiotherapy or an anthracycline containing regimen 3. Patients unfit for chemotherapy or those with neuropathy greater than grade one (sensory or motor) 4. Known allergy to platinum compounds or to mannitol 5. Known sensitivity to taxanes 6. Previous exposure to a taxane in adjuvant chemotherapy within 12 months of trial entry 7. Previous treatment with a taxane for recurrent/metastatic disease 8. Previous treatment with a platinum chemotherapy drug 9. LFTs: abnormal bilirubin (greater than ULN), AST and/or ALT greater than 3 x ULN and Alkaline Phosphatase greater than 5 x ULN (or an isolated elevation AST/ALT of greater than or equal to 5 x ULN) 10. Patients with a life expectancy of less than three months 11. Previous malignancies other than adequately treated in situ carcinoma of the uterine cervix or basal or squamous cell carcinoma of the skin, unless there has been a disease free interval of at least ten years 12. Patients with bone limited disease 13. Other serious uncontrolled medical conditions or concurrent medical illness likely to compromise life expectancy and/or the completion of trial therapy 14. Pregnant, lactating or potentially childbearing women not using adequate contraception (documentation of a negative serum Human Choronic Gonadotropin [HCG] pregnancy test should be available for pre-menopausal women with intact reproductive organs, or women less than two years after the menopause. Fertile women and their partners must use a medically acceptable contraceptive throughout the treatment period and for six months following cessation of treatment. Subjects must be made aware before entering the trial of the risk in becoming pregnant) |
| Date of first enrolment | 16/01/2008 |
| Date of final enrolment | 21/03/2014 |
Locations
Countries of recruitment
- United Kingdom
- England
Study participating centre
SE1 9RT
United Kingdom
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/05/2018 | Yes | No | |
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
Editorial Notes
18/02/2019: The following changes were made:
1. The EudraCT number was added.
2. The overall trial end date was changed from 31/07/2018 to 31/03/2020
3. Publication reference added.
30/03/2017: The overall trial end date was changed from 21/03/2016 to 31/07/2018.
17/04/2014: The overall trial end date was changed from 16/01/2014 to 21/03/2016.
18/01/2008: The overall trial start and end dates of the trial were updated. The previous overall trial start and end dates:
1. Overall trial start date: 01/10/2007
2. Overall trial end date: 01/10/2013
The previous sponsor of this trial was the 'Institute of Cancer Research and Guy's and St Thomas's NHS Foundation Trust (UK)'. For details of the current sponsor, please see the sponsor section.
