Clinical trial NCT00532727: Triple Negative Breast Cancer Trial
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
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Breast Cancer
Keywords: Breast Cancer
Triple Negative
Lead sponsor: Institute of Cancer Research, United Kingdom
Sponsor class: OTHER
Collaborators: name: King's College London
name: Cancer Research UK
name: Breakthrough Breast Cancer
First posted: 2007-09-20
Enrollment: 400
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: 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.
timeFrame: Time from start of treatment to 18 weeks
Secondary outcomes:
measure: 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
timeFrame: Time from start of treatment until confirmation of progression
measure: 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.
timeFrame: Time from start of treatment until confirmation of progression or death
measure: 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
timeFrame: Time from randomisation to discontinuation of protocol treatment for any reason, or progression of disease
measure: Overall survival: this will be defined as time from randomisation until death from any cause in the intention to treat population
timeFrame: Time from randomisation until death from any cause
measure: 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)
timeFrame: Time from start of treatment to 18 weeks
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Guy's and St Thomas' Hospital NHS Foundation Trust
Study officials:
affiliation: King's College London
name: Andrew Tutt, MB ChB, MRCP, FRCR, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.