Triple Negative Breast Cancer Trial (TNT)

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.

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.

Study Overview

• Status: Unknown
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Carboplatin; Drug: Docetaxel

• Study Type: Interventional
• Enrollment (Anticipated): 400
• Phase: Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SE1 9RT
    • Guy's and St Thomas' Hospital NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; Carboplatin	Drug: Carboplatin; AUC 6 every 3 weeks for six cycles (18 weeks)
Active Comparator: Arm B; Docetaxel	Drug: Docetaxel; 100mg/m2 every 3 weeks for six cycles (18 weeks)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 from start of treatment to 18 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
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 from start of treatment until 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 from start of treatment until 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	Time from randomisation to discontinuation of protocol treatment for any reason, or progression of disease
Overall survival: this will be defined as time from randomisation until death from any cause in the intention to treat population	Time from randomisation until death from any cause
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 from start of treatment to 18 weeks

Collaborators and Investigators

• Sponsor: Institute of Cancer Research, United Kingdom
• Collaborators: King's College London; Cancer Research UK; Breakthrough Breast Cancer
• Investigators: Principal Investigator: Andrew Tutt, MB ChB, MRCP, FRCR, PhD, King's College London

Publications and helpful links

General Publications

• 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.
• 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.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2008
• Primary Completion (Actual): March 1, 2016
• Study Completion (Anticipated): March 1, 2020

Study Registration Dates

• First Submitted: September 19, 2007
• First Submitted That Met QC Criteria: September 19, 2007
• First Posted (Estimate): September 20, 2007

Study Record Updates

• Last Update Posted (Actual): February 20, 2019
• Last Update Submitted That Met QC Criteria: February 18, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Breast Cancer; Triple Negative
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel; Carboplatin
• Other Study ID Numbers: ICR-CTSU/2006/10003; ISRCTN97330959; Main REC: 07/Q0603/67; CTA: 22138/0004/001-0001; EudraCT Number: 2006-004470-26