Condition category
Cancer
Date applied
26/01/2007
Date assigned
20/03/2007
Last edited
17/04/2014
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

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

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.

Please note that as of the 18/01/2008 this trial record has been updated. All details of updates can be found in the relevant section under the date 18/01/2008. Please also note that the start and end dates of the trial have also been changed. The previous anticipated start and end dates are as follows:
Anticipated start date: 01/10/2007
Anticipated 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.

On 17/04/2014 the anticipated end date was changed from 16/01/2014 to 21/03/2016

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

Not specified

Trial type

Treatment

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 measures

Response:
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

21/03/2016

Reason abandoned

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

Not Specified

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

21/03/2016

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

http://www.icr.ac.uk/

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

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes