A Randomised 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
概览
- 阶段
- 2 期
- 干预措施
- Tamoxifen
- 疾病 / 适应症
- ER+ Breast Cancer
- 发起方
- Royal Marsden NHS Foundation Trust
- 入组人数
- 1100
- 试验地点
- 48
- 主要终点
- Incidence of positive ctDNA result at first test (Surveillance phase)
- 状态
- 招募中
- 最后更新
- 去年
概览
简要总结
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.
详细描述
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.
研究者
入排标准
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Standard endocrine therapy
Standard endocrine therapy will continue for up to 24 months on trial. Standard endocrine therapies include tamoxifen, and aromatase inhibitors (letrozole, anastrazole, exemestane).
干预措施: Tamoxifen
Standard endocrine therapy
Standard endocrine therapy will continue for up to 24 months on trial. Standard endocrine therapies include tamoxifen, and aromatase inhibitors (letrozole, anastrazole, exemestane).
干预措施: Letrozole
Standard endocrine therapy
Standard endocrine therapy will continue for up to 24 months on trial. Standard endocrine therapies include tamoxifen, and aromatase inhibitors (letrozole, anastrazole, exemestane).
干预措施: Exemestane
Standard endocrine therapy
Standard endocrine therapy will continue for up to 24 months on trial. Standard endocrine therapies include tamoxifen, and aromatase inhibitors (letrozole, anastrazole, exemestane).
干预措施: Anastrozole
Palbociclib and fulvestrant
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.
干预措施: Palbociclib 125Mg Tab
Palbociclib and fulvestrant
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.
干预措施: Fulvestrant injection
结局指标
主要结局
Incidence of positive ctDNA result at first test (Surveillance phase)
时间窗: Start of study
Test during the surveillance phase detects presence of ctDNA in the first test
Relapse free survival (Treatment phase)
时间窗: 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)
时间窗: Up to 36 months from entry to study
Test during the surveillance phase detects presence of ctDNA
次要结局
- EQ-5D-5L quality of life assessment: Self-care element(up to 24 months from randomisation)
- Frequency and Severity of adverse events(up to 24 months from randomisation)
- Invasive disease free survival(up to 60 months from randomisation)
- EQ-5D-5L quality of life assessment: Usual activities element(up to 24 months from randomisation)
- Overall survival(up to 60 months from randomisation)
- EQ-5D-5L quality of life assessment: Pain/ Discomfort element(up to 24 months from randomisation)
- Distant recurrence free survival(up to 60 months from randomisation)
- EQ-5D-5L quality of life assessment: Mobility element(up to 24 months from randomisation)
- EQ-5D-5L quality of life assessment: Anxiety/ Depression element(up to 24 months from randomisation)
- EQ-5D-5L quality of life assessment: Visual Analogue Scale(up to 24 months from randomisation)