Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Bone Density Conservation Agents

Antineoplastic Agents

All Drugs and Chemicals

Pharmaceutical Solutions

Tamoxifen

Fulvestrant

Exemestane

Letrozole

Palbociclib

Anastrozole

Aromatase Inhibitors

Enzyme Inhibitors

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Estrogen Receptor Modulators

Selective Estrogen Receptor Modulators

Protein Kinase Inhibitors

Standard endocrine therapy will continue for up to 24 months on trial.

Standard endocrine therapies include tamoxifen, and aromatase inhibitors (letrozole, anastrazole, exemestane).

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.

Palbociclib Tablets, 125 mg orally once daily, beginning on Cycle 1, on Days 1-21 of each 28-day cycle.

Palbociclib 125Mg Tab

Fulvestrant 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.

Fulvestrant injection

Project Manager

Anne Patsouris

PI, Dr Marie Vallee

Dr Julien Grenier

Oliver Arsene

Monica Arnedos

PI: Dr Xavier Durando

Sylvain Ladoire

Elise Bonnet

Dominque Genet

Elise Deluche

Dr Thomas Bachelot

Dr Renaud Sabatier

PI: Dr Marie Robert

PI: Dr Caroline Bailleux

Fabrice Andre

Mahasti Saghatchian

Dr Christelle Jouannaud

Dr Fanny Le Du

Marianne Leheurteur

Gilles Freyer

Dr Florence Dolenc

Duncan Wheatley

PI: Dr Amit Chakrabarti

Jeremy Braybrooke

PI: Dr Cheryl Palmer

PI: Professor Carlo Palmieri

PI: Dr Peter Hall

PI: Dr Andreas Makris

PI: Dr Rebecca Roylance

Nicholas Turner

PI: Dr Ciara O'Brien

Sarah Khan, PI

PI: Dr Mark Tuthill

PI: Sarah Ayers

Matthew Winter

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.

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.

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

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

Test during the surveillance phase detects presence of ctDNA

Test during the surveillance phase detects presence of ctDNA in the first test

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 (AEs) assessed as per CTCAE v5

Time from randomisation to death from any cause

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.

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.

Spots Global Cancer Trial Database for palbociclib 125mg tab