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Triple Negative Breast Cancer Trial (TNT)

Primary Purpose

Breast Cancer

Status
Unknown status
Phase
Phase 3
Locations
United Kingdom
Study Type
Interventional
Intervention
Carboplatin
Docetaxel
Sponsored by
Institute of Cancer Research, United Kingdom
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring Breast Cancer, Triple Negative

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Histologically confirmed ER-, PR-, primary breast cancer
  • Histologically confirmed HER2- primary breast cancer
  • Measurable confirmed metastatic or recurrent locally advanced disease unsuitable for local therapy but suitable for taxane chemotherapy
  • Patients with stable, treated bain metastases will be eligible providing informed consent can be given and that other sites of measurable disease are present.
  • Patients with bone metastases currently receiving bisphosphonates for palliation will be eligible providing informed consent can be given and that other sites of measurable disease are present
  • ECOG Performance Status 0, 1, or 2
  • Adequate haematology, biochemical indices (FBC, U & Es)
  • LFTs = Normal bilirubin, AST and/or ALT = 3 x ULN if Alk Phos >5 x ULN (or an isolated elevation AST/ALT of ≤5 x ULN
  • Adequate renal function - Creatinine clearance of >25mls per minute
  • Written informed consent, able to comply with treatment and follow up

Exclusion Criteria:

  • Original primary tumour or subsequent relapse known to be positive for any of ER, PR, or HER2 receptors
  • Patients unfit for chemotherapy or those with neuropathy >grade 1 (sensory or motor)
  • Known allergy to platinum compounds or to mannitol
  • Known sensitivity to taxanes
  • Patients with inoperable locally advanced disease suitable for local radiotherapy or an anthracycline containing regimen
  • Previous chemotherapy for metastatic disease other than an anthracycline as in inclusion criteria above
  • Previous exposure to a taxane in adjuvant chemotherapy within 12 months of trial entry
  • Previous treatment with a taxane for recurrent locally advanced disease
  • Previous treatment with a platinum chemotherapy drug
  • LFTs = Abnormal bilirubin (> ULN), AST and/or ALT >3 X ULN and Alk Phos >5 x ULN (or an isolated elevation AST/ALT of >5 x ULN)
  • Patients with a life expectancy of less than 3 months
  • Previous malignancies other than adequately treated in situ carcinoma of the uterine cervix or basal or squamous call carcinoma of the skin, unless there has been a disease free interval of at least 10 years
  • Previous or synchronous second breast cancer (unless also confirmed ER-, PR- and HER2-)
  • Patients with bone limited disease
  • Other serious uncontrolled medical conditions or concurrent medical illness likely to compromise life expectancy and/or the completion of trial therapy
  • Pregnant, lactating or potentially childbearing women not using adequate contraception

Sites / Locations

  • Guy's and St Thomas' Hospital NHS Foundation Trust

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm A

Arm B

Arm Description

Carboplatin

Docetaxel

Outcomes

Primary Outcome Measures

Response: Response will be evaluated after three and six cycles of chemotherapy using modified Response Evaluation Criteria in Solid Tumours (RECIST) criteria, with appropriate clinical assessment and radiological investigations.

Secondary Outcome Measures

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
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.
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
Overall survival: this will be defined as time from randomisation until death from any cause in the intention to treat population
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)

Full Information

First Posted
September 19, 2007
Last Updated
February 18, 2019
Sponsor
Institute of Cancer Research, United Kingdom
Collaborators
King's College London, Cancer Research UK, Breakthrough Breast Cancer
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1. Study Identification

Unique Protocol Identification Number
NCT00532727
Brief Title
Triple Negative Breast Cancer Trial
Acronym
TNT
Official Title
Triple Negative Trial: A Randomised Phase III Trial of Carboplatin Compared to Docetaxel for Patients With Metastatic or Recurrent Locally Advanced ER-, PR- and HER2- Breast Cancer.
Study Type
Interventional

2. Study Status

Record Verification Date
February 2019
Overall Recruitment Status
Unknown status
Study Start Date
January 2008 (Actual)
Primary Completion Date
March 2016 (Actual)
Study Completion Date
March 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institute of Cancer Research, United Kingdom
Collaborators
King's College London, Cancer Research UK, Breakthrough Breast Cancer

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to determine whether there is greater activity for carboplatin than a taxane standard of care (docetaxel) in women with ER-, PR- and HER2- breast cancer. The trial aims to recruit between 370 and 450 patients.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
Keywords
Breast Cancer, Triple Negative

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
400 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm A
Arm Type
Experimental
Arm Description
Carboplatin
Arm Title
Arm B
Arm Type
Active Comparator
Arm Description
Docetaxel
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Intervention Description
AUC 6 every 3 weeks for six cycles (18 weeks)
Intervention Type
Drug
Intervention Name(s)
Docetaxel
Intervention Description
100mg/m2 every 3 weeks for six cycles (18 weeks)
Primary Outcome Measure Information:
Title
Response: Response will be evaluated after three and six cycles of chemotherapy using modified Response Evaluation Criteria in Solid Tumours (RECIST) criteria, with appropriate clinical assessment and radiological investigations.
Time Frame
Time from start of treatment to 18 weeks
Secondary Outcome Measure Information:
Title
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
Time Frame
Time from start of treatment until confirmation of progression
Title
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.
Time Frame
Time from start of treatment until confirmation of progression or death
Title
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
Time Frame
Time from randomisation to discontinuation of protocol treatment for any reason, or progression of disease
Title
Overall survival: this will be defined as time from randomisation until death from any cause in the intention to treat population
Time Frame
Time from randomisation until death from any cause
Title
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)
Time Frame
Time from start of treatment to 18 weeks

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically confirmed ER-, PR-, primary breast cancer Histologically confirmed HER2- primary breast cancer Measurable confirmed metastatic or recurrent locally advanced disease unsuitable for local therapy but suitable for taxane chemotherapy Patients with stable, treated bain metastases will be eligible providing informed consent can be given and that other sites of measurable disease are present. Patients with bone metastases currently receiving bisphosphonates for palliation will be eligible providing informed consent can be given and that other sites of measurable disease are present ECOG Performance Status 0, 1, or 2 Adequate haematology, biochemical indices (FBC, U & Es) LFTs = Normal bilirubin, AST and/or ALT = 3 x ULN if Alk Phos >5 x ULN (or an isolated elevation AST/ALT of ≤5 x ULN Adequate renal function - Creatinine clearance of >25mls per minute Written informed consent, able to comply with treatment and follow up Exclusion Criteria: Original primary tumour or subsequent relapse known to be positive for any of ER, PR, or HER2 receptors Patients unfit for chemotherapy or those with neuropathy >grade 1 (sensory or motor) Known allergy to platinum compounds or to mannitol Known sensitivity to taxanes Patients with inoperable locally advanced disease suitable for local radiotherapy or an anthracycline containing regimen Previous chemotherapy for metastatic disease other than an anthracycline as in inclusion criteria above Previous exposure to a taxane in adjuvant chemotherapy within 12 months of trial entry Previous treatment with a taxane for recurrent locally advanced disease Previous treatment with a platinum chemotherapy drug LFTs = Abnormal bilirubin (> ULN), AST and/or ALT >3 X ULN and Alk Phos >5 x ULN (or an isolated elevation AST/ALT of >5 x ULN) Patients with a life expectancy of less than 3 months Previous malignancies other than adequately treated in situ carcinoma of the uterine cervix or basal or squamous call carcinoma of the skin, unless there has been a disease free interval of at least 10 years Previous or synchronous second breast cancer (unless also confirmed ER-, PR- and HER2-) Patients with bone limited disease Other serious uncontrolled medical conditions or concurrent medical illness likely to compromise life expectancy and/or the completion of trial therapy Pregnant, lactating or potentially childbearing women not using adequate contraception
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrew Tutt, MB ChB, MRCP, FRCR, PhD
Organizational Affiliation
King's College London
Official's Role
Principal Investigator
Facility Information:
Facility Name
Guy's and St Thomas' Hospital NHS Foundation Trust
City
London
ZIP/Postal Code
SE1 9RT
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
29713086
Citation
Tutt A, Tovey H, Cheang MCU, Kernaghan S, Kilburn L, Gazinska P, Owen J, Abraham J, Barrett S, Barrett-Lee P, Brown R, Chan S, Dowsett M, Flanagan JM, Fox L, Grigoriadis A, Gutin A, Harper-Wynne C, Hatton MQ, Hoadley KA, Parikh J, Parker P, Perou CM, Roylance R, Shah V, Shaw A, Smith IE, Timms KM, Wardley AM, Wilson G, Gillett C, Lanchbury JS, Ashworth A, Rahman N, Harries M, Ellis P, Pinder SE, Bliss JM. Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial. Nat Med. 2018 May;24(5):628-637. doi: 10.1038/s41591-018-0009-7. Epub 2018 Apr 30.
Results Reference
background
PubMed Identifier
33098992
Citation
Sipos O, Tovey H, Quist J, Haider S, Nowinski S, Gazinska P, Kernaghan S, Toms C, Maguire S, Orr N, Linn SC, Owen J, Gillett C, Pinder SE, Bliss JM, Tutt A, Cheang MCU, Grigoriadis A. Assessment of structural chromosomal instability phenotypes as biomarkers of carboplatin response in triple negative breast cancer: the TNT trial. Ann Oncol. 2021 Jan;32(1):58-65. doi: 10.1016/j.annonc.2020.10.475. Epub 2020 Oct 21.
Results Reference
derived
Links:
URL
https://www.icr.ac.uk/our-research/centres-and-collaborations/centres-at-the-icr/clinical-trials-and-statistics-unit/clinical-trials/tnt
Description
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Triple Negative Breast Cancer Trial

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