A Trial of Early Detection of Molecular Relapse With Circulating Tumour DNA Tracking and Treatment With Palbociclib Plus Fulvestrant Versus Standard Endocrine Therapy in Patients With ER Positive HER2 Negative Breast Cancer
- Conditions
- ER+ Breast CancerHER2-negative Breast Cancer
- Interventions
- Registration Number
- NCT04985266
- Lead Sponsor
- Royal Marsden NHS Foundation Trust
- Brief Summary
Detection of molecular relapse with circulating tumour DNA analysis can identify which patients with ER positive breast cancer are relapsing on adjuvant endocrine therapy. This trial will aim to demonstrate that palbociclib and fulvestrant, can defer or prevent relapse in patients with ctDNA detected molecular relapse.
The TRAK-ER trial will have two phases, a ctDNA surveillance phase and a randomised therapy trial in patients with positive ctDNA.
The TRAK-ER trial will establish a ctDNA screening programme for patients with ER positive breast cancer receiving adjuvant endocrine therapy with at least a further three years of standard adjuvant endocrine therapy planned. Patients recruited into the TRAK-ER study will have high-risk clinical features to identify patients at higher risk of future relapse.
ctDNA assays will be used to identify which people are at very high risk of relapse (i.e. those with a positive ctDNA result), and randomise this high risk population between standard endocrine therapy versus palbociclib plus fulvestrant for up to two years.
- Detailed Description
The TRAK-ER trial is a multi-centre, randomised, open-label trial in patients with early stage oestrogen reception positive (ER+) human epidermal growth receptor-2 negative (HER2-) breast cancer, whom have detectable circulating DNA (ctDNA) but no overt macroscopic disease on imaging. TRAK-ER aims to demonstrate that fulvestrant plus palbociclib improves relapse free survival compared to standard endocrine therapy in this patient group.
Despite current treatment, patients with ER+HER2- breast cancer are considered high-risk of distant recurrence for more than the first two decades after initial diagnosis. ctDNA analysis provides a non-invasive, serial source of tumour material which can monitor tumour dynamics and detect molecular relapse.
TRAK-ER will be split into two phases, the first surveillance phase aims to investigate the use of ctDNA to identify and predict the risk of molecular relapse in early ER+/HER2- breast cancer patients whom are receiving adjuvant endocrine therapy with no overt macroscopic disease on imaging. Using ctDNA assays, patients enrolled on TRAK-ER will receive ctDNA testing on a three-monthly basis for up to three years. In the instance where ctDNA is detected, imaging will determine whether overt disease is present. If a patient had a positive ctDNA detection and no macroscopic disease on the staging scan, the patient will be randomised to one of the treatment groups in the second phase of TRAK-ER, the treatment phase.
The treatment phase of TRAK-ER will be a randomised, open-label study which aims to determine whether fulvestrant plus palbociclib (intervention arm) improves relapse free survival compared to standard endocrine therapy (control arm) in patients carried through from the surveillance phase. Patients on each arm will receive treatment (fulvestrant plus palbociclib or standard endocrine therapy) for up to 24 months. Six monthly imaging will determine the presence of macroscopic disease. If macroscopic disease is observed, the patient will discontinue TRAK-ER treatment and commence standard therapy outside of the TRAK-ER trial.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 1100
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Palbociclib and fulvestrant Fulvestrant injection Treatment with palbociclib plus fulvestrant will continue for a maximum of 24 months. Palbociclib will be given orally once a day on days 1-21 of each 28 day cycle. Fulvestrant 500 mg will be administered on cycle 1 days 1 and 15, cycle 2 day 1 and then every 28 days thereafter (plus or minus 3 days) as two intramuscular injections of 250mg fulvestrant at each visit. Standard endocrine therapy Tamoxifen Standard endocrine therapy will continue for up to 24 months on trial. Standard endocrine therapies include tamoxifen, and aromatase inhibitors (letrozole, anastrazole, exemestane). Standard endocrine therapy Letrozole Standard endocrine therapy will continue for up to 24 months on trial. Standard endocrine therapies include tamoxifen, and aromatase inhibitors (letrozole, anastrazole, exemestane). Standard endocrine therapy Anastrozole Standard endocrine therapy will continue for up to 24 months on trial. Standard endocrine therapies include tamoxifen, and aromatase inhibitors (letrozole, anastrazole, exemestane). Palbociclib and fulvestrant Palbociclib 125Mg Tab Treatment with palbociclib plus fulvestrant will continue for a maximum of 24 months. Palbociclib will be given orally once a day on days 1-21 of each 28 day cycle. Fulvestrant 500 mg will be administered on cycle 1 days 1 and 15, cycle 2 day 1 and then every 28 days thereafter (plus or minus 3 days) as two intramuscular injections of 250mg fulvestrant at each visit. Standard endocrine therapy Exemestane Standard endocrine therapy will continue for up to 24 months on trial. Standard endocrine therapies include tamoxifen, and aromatase inhibitors (letrozole, anastrazole, exemestane).
- Primary Outcome Measures
Name Time Method Incidence of positive ctDNA result at first test (Surveillance phase) Start of study Test during the surveillance phase detects presence of ctDNA in the first test
Relapse free survival (Treatment phase) 60 months from randomisation Time from randomization to invasive local/regional recurrence (including ipsilateral invasive breast recurrence) or distant recurrence or death from any cause. Patients with second primary invasive cancers (breast or non-breast) would be censored at time of detection.
Incidence of positive ctDNA result during surveillance (Surveillance phase) Up to 36 months from entry to study Test during the surveillance phase detects presence of ctDNA
- Secondary Outcome Measures
Name Time Method EQ-5D-5L quality of life assessment: Self-care element up to 24 months from randomisation Assessed using the 5-point scale.
Frequency and Severity of adverse events up to 24 months from randomisation Frequency and severity of Adverse Events (AEs) assessed as per CTCAE v5
Invasive disease free survival up to 60 months from randomisation Time from randomisation to invasive local/regional recurrence (including ipsilateral invasive breast recurrence), new breast cancer (ipsilateral or contralateral) or distant recurrence or death from any cause. Patients with non-invasive recurrences or second primary invasive cancers (non-breast) would be censored at time of detection.
EQ-5D-5L quality of life assessment: Usual activities element up to 24 months from randomisation Assessed using the 5-point scale.
Overall survival up to 60 months from randomisation Time from randomisation to death from any cause
EQ-5D-5L quality of life assessment: Pain/ Discomfort element up to 24 months from randomisation Assessed using the 5-point scale.
EQ-5D-5L quality of life assessment: Mobility element up to 24 months from randomisation Assessed using the 5-point scale.
Distant recurrence free survival up to 60 months from randomisation Time from randomization to distant invasive breast cancer recurrence or death from any cause. Patients with new contralateral invasive breast cancers or second primary invasive non-breast cancers would be censored at time of detection.
EQ-5D-5L quality of life assessment: Anxiety/ Depression element up to 24 months from randomisation Assessed using the 5-point scale.
EQ-5D-5L quality of life assessment: Visual Analogue Scale up to 24 months from randomisation Assessed using 0-100 scale.
Trial Locations
- Locations (48)
Barnet Hospital
🇬🇧London, Barnet, United Kingdom
Royal Sussex Hospital
🇬🇧Brighton, United Kingdom
Velindre Cancer Centre
🇬🇧Cardiff, United Kingdom
Velindre University NHS Trust
🇬🇧Cardiff, United Kingdom
Darlington Memorial Hospital
🇬🇧Darlington, United Kingdom
Western General
🇬🇧Edinburgh, United Kingdom
Royal Devon and Exeter Hospital
🇬🇧Exeter, United Kingdom
Beatson West of Scotland Cancer Centre
🇬🇧Glasgow, United Kingdom
St James's University Hospital
🇬🇧Leeds, United Kingdom
The Royal Free Hospital
🇬🇧London, United Kingdom
Maidstone Hospital
🇬🇧Maidstone, United Kingdom
Derriford Hospital - UHPNT
🇬🇧Plymouth, United Kingdom
Somerset NHS Foundation Trust
🇬🇧Taunton, United Kingdom
Institut de Cancérologie de l'Ouest
🇫🇷Nantes, France
Centre Hospitalier Annecy Genevois_Site d'Annecy
🇫🇷Annecy, France
Institut du Cancer Avignon Sainte Catherine
🇫🇷Avignon, France
Centre Hospitalier Simone Veil de Blois
🇫🇷Blois, France
Institut Bergonié
🇫🇷Bordeaux, France
Centre Jean Perrin
🇫🇷Clermont Ferrand, France
Centre George François Leclerc
🇫🇷Dijon, France
Groupe Hospitalier Mutualiste de Grenoble
🇫🇷Grenoble, France
Clinique Chénieux
🇫🇷Limoges, France
Centre Hospitalier Universitaire de Limoges
🇫🇷Limoges, France
Centre Léon Bérard
🇫🇷Lyon, France
Institut Paoli Calmettes
🇫🇷Marseille, France
Centre Antoine Lacassagne
🇫🇷Nice, France
Gustave Roussy Cancer Campus
🇫🇷Paris, France
Hôpital Américain de Paris
🇫🇷Paris, France
Institut Godinot
🇫🇷Reims, France
Centre Eugène Marquis
🇫🇷Rennes, France
Centre Henri Becquerel
🇫🇷Rouen, France
CHU de Saint Etienne-Institut de Cancérologie
🇫🇷Saint-Priest-en-Jarez, France
Institut Claudius Regaud
🇫🇷Toulouse, France
Royal Cornwall Hospitals NHS Trust
🇬🇧Truro, Cornwall, United Kingdom
University Hospitals Dorset: Royal Bournemouth Hospital
🇬🇧Bournemouth, United Kingdom
Bristol Haematology and Oncology Centre
🇬🇧Bristol, United Kingdom
North West Anglia NHS Foundation Trust: Hinchingbrooke Hospital
🇬🇧Huntingdon, United Kingdom
The Clatterbridge Cancer Centre NHS Foundation Trust
🇬🇧Liverpool, United Kingdom
Barts Health NHS Trust
🇬🇧London, United Kingdom
Mount Vernon Hospital
🇬🇧London, United Kingdom
University College London Hospital
🇬🇧London, United Kingdom
The Royal Marsden NHS Foundation Trust
🇬🇧London, United Kingdom
The Christie NHS Foundation Trust
🇬🇧Manchester, United Kingdom
Nottingham University Hopsitals NHS Trust
🇬🇧Nottingham, United Kingdom
Oxford Cancer & Haematology Centre, Churchill Hospital,
🇬🇧Oxford, United Kingdom
North West Anglia NHS Foundation Trust: Peterborough Hospital
🇬🇧Peterborough, United Kingdom
University Hospitals Dorset: Poole Hospital
🇬🇧Poole, United Kingdom
Weston Park Hospital
🇬🇧Sheffield, United Kingdom