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
EudraCT/CTIS number	2006-004470-26
ClinicalTrials.gov number	NCT00532727
Secondary identifying numbers	ICR-CTSU/2006/10003

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

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

http://www.cancerhelp.org.uk/trials/a-trial-comparing-different-chemotherapy-drugs-for-advanced-triple-negative-breast-cancer

Contact information

Dr Andrew Tutt
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
Email	andrew.tutt@icr.ac.uk

Study information

Study design	Phase III multicentre randomised 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 to request a patient 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 concentrationtime 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
Pharmaceutical study type(s)
Phase	Phase III
Drug / device / biological / vaccine name(s)	Carboplatin, docetaxel
Primary outcome measure	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.
Secondary outcome measures	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 2. Progression free survival: this will be defined according to RECIST criteria and will be measured from the start of treatment until the confirmation of progression or death. Response to second line therapy on progression will be assessed using RECIST criteria as described for the primary endpoint 3. Time to treatment failure: this will be defined as time from randomisation to discontinuation of protocol treatment for any reason, or progression of disease as defined by RECIST 4. Overall survival: this will be defined as time from randomisation until death from any cause in the intention to treat population 5. Toxicity will be assessed throughout the treatment period using the National Cancer Institute Common Terminology Criteria for Adverse Events version three (NCI CTCAE v3.0).
Overall study start date	16/01/2008
Completion date	31/03/2020

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Female
Target number of participants	350 - 450 patients
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

England
United Kingdom

Study participating centre

Guy's & St Thomas' Hospital NHS Foundation Trust

London
SE1 9RT
United Kingdom

Sponsor information

Institute of Cancer Research and King's College London (UK)
Research organisation

c/o Sarah Kernaghan
Institute of Cancer Research
123 Old Brompton Road
London
SW7 3RP
United Kingdom

Phone	+44 (0)20 8722 4152
Email	tnt-icrctsu@icr.ac.uk
Website	http://www.icr.ac.uk/
"ROR"	https://ror.org/0220mzb33

Funders

Funder type

Charity

Cancer Research UK (UK)
Private sector organisation / Other non-profit organizations

Alternative name(s): CR_UK, Cancer Research UK - London, CRUK
Location: United Kingdom

Breakthrough Breast Cancer (UK)
Private sector organisation / Other non-profit organizations

Location: United Kingdom

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?
Results article	results	01/05/2018		Yes	No

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.