The UK Plasma Based Molecular Profiling of Advanced Breast Cancer to Inform Therapeutic CHoices (plasmaMATCH) Trial
plasmaMATCH
A Multiple Parallel Cohort, Multi-centre Phase IIa Trial Aiming to Provide Proof of Principle Efficacy for Designated Targeted Therapies in Patients With Advanced Breast Cancer Where the Targetable Mutation is Identified Through ctDNA
1 other identifier
interventional
1,150
1 country
19
Brief Summary
plasmaMATCH is a multi-centre phase IIa umbrella trial platform consisting of a ctDNA screening component and a therapeutic component. plasmaMATCH aims to assess whether ctDNA screening can be used to detect patient subgroups who will be sensitive to targeted therapies, and will also assess the safety and activity of the targeted treatments.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Dec 2016
Longer than P75 for phase_2
19 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
December 15, 2016
CompletedFirst Submitted
Initial submission to the registry
January 10, 2017
CompletedFirst Posted
Study publicly available on registry
June 9, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
November 1, 2023
CompletedJanuary 22, 2019
January 1, 2019
5.9 years
January 10, 2017
January 17, 2019
Conditions
Outcome Measures
Primary Outcomes (1)
The primary endpoint for Cohorts A to E is confirmed objective response rate as defined by RECIST v1.1 for each cohort separately
up to 24 weeks
Secondary Outcomes (9)
Clinical benefit rate
up to 24 weeks
Progression free survival
up to 24 weeks
Incidence of treatment-emergent adverse events (safety and tolerability)
through study completion, estimated average 1 year
Duration of response for each cohort
through study completion, estimated average 1 year
Frequency of mutations identified in ctDNA screening
Baseline
- +4 more secondary outcomes
Study Arms (5)
Cohort A - Extended-dose fulvestrant
EXPERIMENTALFulvestrant 500mg IM on Cycle 1 Days 1, 8 and 15 and Cycle 2 onwards Days 1 and 15
Cohort B - Neratinib
EXPERIMENTALNeratinib 240mg PO on a continuous schedule starting on Cycle 1 Day 1 AND in ER positive breast cancer, fulvestrant 500mg IM on Cycle 1 Days 1 and 15 and Cycle 2 onwards Day 1
Cohort C - AZD5363 and fulvestrant
EXPERIMENTALAZD5363 400mg PO BID on a 7 day schedule of 4 days on treatment followed by 3 days off treatment AND fulvestrant 500mg IM Cycle 1 Days 1 and 15 and Cycle 2 onwards Day 1
Cohort D - AZD5363
EXPERIMENTALAZD5363 480mg PO BID on a 7 day schedule of 4 days on treatment followed by 3 days off treatment
Cohort E - olaparib and AZD6738
EXPERIMENTALAZD6738 160mg to be administered once daily on Days 1-7 of each cycle and olaparib 300mg to be administered twice daily on a continuous schedule starting on Cycle 1 Day 1.
Interventions
Eligibility Criteria
You may qualify if:
- Female.
- Aged ≥ 18 years old.
- Histologically confirmed invasive breast carcinoma.
- Metastatic or recurrent locally advanced breast cancer that is not suitable for treatment with radical or curative intent.
- Demonstrated progression of disease by radiological assessment or by clinical assessment within the last 6 weeks.
- Measurable disease by RECIST v1.1.
- Patients must have completed at least one prior line of treatment for advanced breast cancer and/or relapse within 12 months of completing (neo)adjuvant chemotherapy. Patients with HER2 positive breast cancer must have been treated with at least two courses of HER2 targeted therapy in the advanced setting (or one course if no further courses of HER2 targeted therapy are available locally).
- Patient must either be suitable for a baseline biopsy of recurrent disease or have an archival biopsy of recurrent disease available. Patients are requested to consent to a baseline biopsy but if deemed unsafe by the Investigator, an archival biopsy of recurrent disease can be used instead. If it is deemed unsafe to proceed with baseline biopsy, and no archival recurrent disease biopsy is available, the patient will not be eligible for entry into the treatment cohort.
- ECOG performance status ≤ 2.
- Life expectancy \>3 months in Cohorts A-D, \>16 weeks in Cohort E.
- Patients must be a) surgically sterile; b) have a sterilised sole partner; c) be postmenopausal; d) must agree to practice true abstinence; or e) must agree to use effective contraception during the period of trial treatment and be willing to do so for 6 months following the end of trial treatment. Effective contraception is defined as double barrier contraception (e.g. condom plus spermicide in combination with a diaphragm, cervical cap or intrauterine device). Ovarian suppression with an LHRH agonist is not a method of contraception.
- Patients of childbearing potential should have a negative serum pregnancy test within 14 days prior to initiation of trial treatment.
- At least 4 weeks washout period after the end of trial treatment on a different cohort within plasmaMATCH.
- Adequate haematological, renal and hepatic function as defined by cohort-specific criteria in protocol.
- For patients with ER positive breast cancer in Cohorts A, B and C: EITHER postmenopausal, as defined by at least one of the following criteria: Age \>60 years; Age \<60 years and cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and serum estradiol and follicle stimulating hormone (FSH) level within the laboratory's reference range for postmenopausal females; Documented bilateral oophorectomy; medically confirmed ovarian failure. OR Pre-/peri-menopausal (i.e. not meeting the criteria for being postmenopausal) if being treated with an LHRH agonist that was commenced at least 4 weeks prior to Cycle 1 Day 1, and continues on the LHRH agonist throughout the trial period.
- +1 more criteria
You may not qualify if:
- Prior treatment with radiotherapy (except for palliative reasons), endocrine therapy, immunotherapy, chemotherapy or IMPs during the previous 4 weeks (6 weeks for nitrosoureas, Mitomycin-C) before trial treatment, except for hormonal therapy with LHRH analogues, which are permitted, and bisphosphonates or RANK ligand antibodies that are permitted for the management of bone metastases.
- Uncontrolled CNS disease (brain metastases or leptomeningeal disease). Patients with prior diagnosis of CNS metastases must be stable by clinical assessment having ceased steroids after prior treatment.
- History of clinically significant or uncontrolled cardiac disease, including congestive heart failure, angina, myocardial infarction within the last 6 months or ventricular arrhythmia. Patients with a history of any of the above listed cardiac conditions judged not to be clinically significant by the local investigator must be notified to the trial team at the ICR-CTSU for approval by the CI and/or Cohort Lead.
- Ongoing toxic manifestations of previous treatments Grade ≥1. Exceptions to this are alopecia or toxicities which in the opinion of the Investigator should not exclude the patient. Such cases should be clearly documented in the patient's notes by the Investigator.
- Major surgery (excluding minor procedures, e.g. placement of vascular access) within 4 weeks of the first dose of trial treatment.
- Pregnant or breastfeeding.
- Any condition that according to the treating physician may compromise the patient's safety or the conduct of the trial.
- Current malignancies of other types, with the exception of adequately treated in situ carcinoma of the cervix and basal or squamous cell carcinoma of the skin. Cancer survivors, who have undergone potentially curative therapy for a prior malignancy and have no evidence of the disease for 3 years or more are eligible for the trial.
- NB. Additional eligibility criteria apply for entry into each treatment cohort.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (19)
Royal Marsden Hosital
Sutton, England, SM2 5PT, United Kingdom
Royal Bournemouth Hospital
Bournemouth, United Kingdom
Bristol Haematology and Oncology Centre
Bristol, United Kingdom
Addenbrooke's Hospital
Cambridge, United Kingdom
Velindre Cancer Centre
Cardiff, United Kingdom
Western General Hospital
Edinburgh, United Kingdom
Royal Devon and Exeter Hospital
Exeter, United Kingdom
Beatson West of Scotland Cancer Centre
Glasgow, United Kingdom
Clatterbridge Cancer Centre
Liverpool, United Kingdom
Barts Health Trust
London, United Kingdom
Royal Marsden Hospital
London, United Kingdom
University College Hospital London
London, United Kingdom
Kent Oncology Centre
Maidstone, United Kingdom
Christie Hospital
Manchester, United Kingdom
Churchill Hospital
Oxford, United Kingdom
Derriford Hospital
Plymouth, United Kingdom
Weston Park Hospital
Sheffield, United Kingdom
University Hospitals Southampton NHS Foundation Trust
Southampton, United Kingdom
Royal Cornwall Hospital
Truro, United Kingdom
Related Publications (2)
Kingston B, Cutts RJ, Bye H, Beaney M, Walsh-Crestani G, Hrebien S, Swift C, Kilburn LS, Kernaghan S, Moretti L, Wilkinson K, Wardley AM, Macpherson IR, Baird RD, Roylance R, Reis-Filho JS, Hubank M, Faull I, Banks KC, Lanman RB, Garcia-Murillas I, Bliss JM, Ring A, Turner NC. Genomic profile of advanced breast cancer in circulating tumour DNA. Nat Commun. 2021 Apr 23;12(1):2423. doi: 10.1038/s41467-021-22605-2.
PMID: 33893289DERIVEDTurner NC, Kingston B, Kilburn LS, Kernaghan S, Wardley AM, Macpherson IR, Baird RD, Roylance R, Stephens P, Oikonomidou O, Braybrooke JP, Tuthill M, Abraham J, Winter MC, Bye H, Hubank M, Gevensleben H, Cutts R, Snowdon C, Rea D, Cameron D, Shaaban A, Randle K, Martin S, Wilkinson K, Moretti L, Bliss JM, Ring A. Circulating tumour DNA analysis to direct therapy in advanced breast cancer (plasmaMATCH): a multicentre, multicohort, phase 2a, platform trial. Lancet Oncol. 2020 Oct;21(10):1296-1308. doi: 10.1016/S1470-2045(20)30444-7. Epub 2020 Sep 10.
PMID: 32919527DERIVED
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- OTHER
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 10, 2017
First Posted
June 9, 2017
Study Start
December 15, 2016
Primary Completion
November 1, 2022
Study Completion
November 1, 2023
Last Updated
January 22, 2019
Record last verified: 2019-01