Plain English Summary
Trial website
Contact information
Type
Scientific
Primary contact
Dr Andrew Tutt
ORCID ID
Contact details
Guy's & St Thomas' Hospital NHS Foundation Trust
Breast Unit
St Thomas Street
London
SE1 9RT
United Kingdom
+44 (0)20 7188 4237
andrew.tutt@icr.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
NCT00532727
Protocol/serial number
ICR-CTSU/2006/10003
Study information
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
Acronym
TNT
Study hypothesis
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
East London and the City Research Ethics Committee 1, 11/06/2007
Study design
Phase III multicentre randomised 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 to request a patient information sheet
Condition
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 names
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 trial start date
16/01/2008
Overall trial end date
31/07/2018
Reason abandoned (if study stopped)
Eligibility
Participant 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
Participant type
Patient
Age group
Adult
Gender
Female
Target number of participants
350 - 450 patients
Participant 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)
Recruitment start date
16/01/2008
Recruitment end date
21/03/2014
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Guy's & St Thomas' Hospital NHS Foundation Trust
London
SE1 9RT
United Kingdom
Sponsor information
Organisation
Institute of Cancer Research and King's College London (UK)
Sponsor details
c/o Sarah Kernaghan
Institute of Cancer Research
123 Old Brompton Road
London
SW7 3RP
United Kingdom
+44 (0)20 8722 4152
tnt-icrctsu@icr.ac.uk
Sponsor type
Research organisation
Website
Funders
Funder type
Charity
Funder name
Cancer Research UK (UK)
Alternative name(s)
CRUK
Funding Body Type
private sector organisation
Funding Body Subtype
other non-profit
Location
United Kingdom
Funder name
Breakthrough Breast Cancer (UK)
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
other non-profit
Location
United Kingdom
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
Basic results (scientific)
Publication list