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.
Written informed consent to participate in the trial and to donation of tissue and blood samples
Male or female patients aged 18 years or older
ECOG performance status 0, 1 or 2 (see https://ecog-acrin.org/resources/ecog-performance-status)
Histologically proven primary ER+ (Allred score 6/8 or greater, or stain in ≥10% of cancer cells) and HER2- (immunohistochemistry 0/1+ and/or negative by in situ hybridization) breast cancer as determined by local laboratory
Any concurrent or planned treatment for the current diagnosis of breast cancer other than adjuvant endocrine therapy or a bisphosphonate.
Patients with prior exposure to a CDK 4/6 inhibitor as part of standard of care may enrol only after at least 12 months from completing CDK4/6 therapy.
Prior exposure to therapeutic dose of fulvestrant is not permitted. One subtherapeutic dose of fulvestrant is permitted.
Prior diagnosis of cancer including prior diagnosis of breast cancer in the previous 5 years, other than for non-melanoma carcinoma of the skin or cervical carcinoma in situ
Parallel
Palbociclib 125Mg Tab
DrugPalbociclib Tablets, 125 mg orally once daily, beginning on Cycle 1, on Days 1-21 of each 28-day cycle.
Fulvestrant injection
DrugFulvestrant Intramuscular injections, 500 mg as two injection of 250mg fulvestrant in 5ml solution at each visit. No fulvestrant dose reductions are permitted. Administered on days 1, 15 (plus or minus 3 days), 29 (plus or minus 3 days), and every 28 (plus or minus 3 days) days thereafter.
Tamoxifen
DrugAs per clinical guidelines
Letrozole
DrugAs per clinical guidelines
Exemestane
DrugAs per clinical guidelines
Anastrozole
DrugAs per clinical guidelines
Incidence of positive ctDNA result during surveillance (Surveillance phase)
Test during the surveillance phase detects presence of ctDNA
Incidence of positive ctDNA result at first test (Surveillance phase)
Test during the surveillance phase detects presence of ctDNA in the first test
Relapse free survival (Treatment phase)
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.
Frequency and Severity of adverse events
Frequency and severity of Adverse Events (AEs) assessed as per CTCAE v5
Overall survival
Time from randomisation to death from any cause
Invasive disease free survival
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.
Distant recurrence free survival
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.
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Royal Marsden NHS Foundation Trust
Lead sponsor
Pfizer
Collaborator
AstraZeneca
Collaborator
Institute of Cancer Research, United Kingdom
Collaborator
UNICANCER
Collaborator
Gustave Roussy, Cancer Campus, Grand Paris
Collaborator
Invitae Corporation
Collaborator
