plasmaMATCH: A clinical trial aiming to assess the safety and activity of targeted treatments in patients with advanced breast cancer where the targetable mutation is identified through circulating tumour DNA screening
| ISRCTN | ISRCTN16945804 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN16945804 |
| EudraCT/CTIS number | 2015-003735-36 |
| ClinicalTrials.gov number | NCT03182634 |
| Secondary identifying numbers | 31608 |
- Submission date
- 28/11/2016
- Registration date
- 07/12/2016
- Last edited
- 09/02/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English Summary
Contact information
Ms Katie Wilkinson
Scientific
Scientific
The Institute of Cancer Research Clinical Trials & Statistics Unit
15 Cotswold Road
Sutton
SM2 5NG
United Kingdom
| Phone | +44 20 8722 4754 |
|---|---|
| plasmamatch-icrctsu@icr.ac.uk |
Study information
| Study design | Randomised; Both; Design type: Treatment, Screening, Drug, Cohort study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | The UK plasma based Molecular profiling of Advanced breast cancer to inform Therapeutic Choices (plasmaMATCH) Trial: A multiple parallel cohort, open-label, multi-centre phase IIa clinical 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 screening |
| Study acronym | plasmaMATCH |
| Study hypothesis | Current hypothesis as of 18/01/2019: 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 efficacy of these targeted treatments. Previous hypothesis: plasmaMATCH aims to assess whether ctDNA screening can be used to detect patients with targetable mutations, and will assess the safety and activity of the targeted treatments in patients with targetable mutations identified at ctDNA screening. |
| Ethics approval(s) | South Central - Oxford C Research Ethics Committee, 20/07/2016, ref: 16/SC/0271 |
| Condition | Breast cancer |
| Intervention | Cohort A: ESR1 mutation identified in ctDNA screening treated with extended-dose fulvestrant. 500mg fulvestrant to be administered intramuscularly (IM) on Cycle 1 Days 1, 8 and 15 and Cycle 2 onwards Days 1 and 15. Cohort B: HER2 mutation identified in ctDNA screening in patients with estrogen receptor (ER) positive breast cancer treated with neratinib plus fulvestrant, or in patients with ER negative breast cancer treated with neratinib only. 240mg neratinib to be administered on a continuous schedule starting on Cycle 1 Day 1. In ER positive breast cancer, 500mg fulvestrant to be administered IM on Cycle 1 Days 1 and 15 and Cycle 2 onwards Day 1. Cohort C: AKT1 mutation identified in ctDNA screening in patients with ER positive breast cancer treated with AZD5363 and fulvestrant. 400mg AZD5363 to be administered twice daily on a 7 day schedule of 4 days on treatment followed by 3 days off treatment. 500mg fulvestrant IM Cycle 1 Days 1 and 15 and Cycle 2 onwards Day 1. Cohort D: AKT activation basket with mutations of AKT1 in patients with ER negative breast cancer or AKT2/3 E17K, PIK3R1 or PTEN mutations or homozygous deletion of PTEN in both ER positive and ER negative breast cancer identified in ctDNA screening or in prior tumour sequencing conducted outside of plasmaMATCH, treated with AZD5363. 480mg AZD5363 to be administered twice daily on a 7 day schedule of 4 days on treatment followed by 3 days off treatment. Cohort E: Patients with triple negative breast cancer (TNBC) on their most recent tumour biopsy who do not have a targetable mutation identified by ctDNA screening or tumour sequencing that would allow entry into Cohorts A to D, or who have an actionable mutation identified but are not otherwise eligible for Cohorts A to D, will be invited to enter Cohort E and consenting patients will receive 160mg AZD6738 to be administered once daily on Days 1–7 of each cycle and 300mg olaparib to be administered twice daily on a continuous schedule starting on Cycle 1 Day 1. For each cohort a cycle consists of 28 days. Treatment will continue until disease progression according to RECIST v1.1. Patients will be assessed by CT scan every 8 weeks with assessment of response by RECIST v1.1. After 32 weeks patients will be assessed by CT scan every 12 weeks. |
| Intervention type | Other |
| Primary outcome measure | Confirmed objective response rate as defined by RECIST v1.1 for each cohort separately. A patient will be said to have had an objective response if they have a complete/partial response at any point during trial treatment. |
| Secondary outcome measures | 1. Clinical benefit rate and progression free survival (PFS), defined as complete/partial response or stable disease as defined by RECIST v1.1 lasting at least 24 weeks. PFS will be measured from the date of entry into the treatment cohort until first date of either confirmed progressive disease according to RECIST criteria or death. 2. Safety and tolerability of therapies will be assessed throughout the treatment period using the NCI CTCAE v4.0 3. Duration of response is measured from the time of first documentation of RECIST complete/partial response (whichever status is recorded first) until the first date that recurrence or progressive disease is objectively documented 4. Frequency of mutations identified in ctDNA screening and the proportion of patients with a targetable mutation who enter the therapeutic component 5. Agreement between ctDNA mutation status and tissue mutation status for patients entering the therapeutic component 6. Pharmacokinetics in Cohort A assessed at Cycle 2-4 Day 1 and Cohort B assessed Cycle 1-4 Day 1 |
| Overall study start date | 01/09/2015 |
| Overall study end date | 31/12/2021 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Female |
| Target number of participants | Planned Sample Size: 1150; UK Sample Size: 1150 |
| Total final enrolment | 1051 |
| Participant inclusion criteria | Current inclusion criteria as of 18/01/2019: 1. Female 2. Aged ≥ 18 years old 3. Histologically confirmed invasive breast carcinoma 4. Metastatic or recurrent locally advanced breast cancer that is not suitable for treatment with radical or curative intent 5. Demonstrated progression of disease by radiological assessment or by clinical assessment within the last 6 weeks 6. Measurable disease by RECIST v1.1 7. 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) 8. 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 9. ECOG performance status ≤ 2 10. Life expectancy >3 months in Cohorts A-D and >16 weeks in Cohort E 11. Patients must be a) surgically sterile; b) have a sterilised sole partner; or c) be postmenopausal; or d) must agree to practice true abstinence; or e) use effective contraception during the period of trial treatment and be willing to do so for 6 months following the end of trial treatment 12. Patients of childbearing potential should have a negative serum pregnancy test within 14 days prior to initiation of trial treatment. 13. At least 4 weeks washout period after the end of trial treatment on a different cohort within plasmaMATCH 14. Adequate haematological, renal and hepatic function as defined by cohort-specific criteria in the protocol 15. 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: 15.1. Age >60 years 15.2. 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 15.3. 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. NB. Additional eligibility criteria apply for entry into each treatment cohort. Previous inclusion criteria: 1. Female 2. Aged ≥ 18 years old 3. Histologically confirmed invasive breast carcinoma 4. Metastatic or recurrent locally advanced breast cancer that is not suitable for treatment with radical or curative intent 5. Demonstrated progression of disease by radiological assessment or by clinical assessment within the last 6 weeks 6. Measurable disease by RECIST v1.1 7. 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) 8. 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 9. ECOG performance status ≤ 2 10. Life expectancy >3 months 11. Patients must be surgically sterile, be postmenopausal or 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 12. Patients of childbearing potential should have a negative serum pregnancy test within 14 days prior to initiation of trial treatment. 13. At least 4 weeks washout period after the end of trial treatment on a different cohort within plasmaMATCH 14. Adequate haematological, renal and hepatic function as defined by: 14.1. Haematology: - Absolute neutrophil count (ANC) ≥1000/mm3 (≥1.0 x 109/L) - Platelet count ≥100,000/mm3 (≥100 x 109/L) - Haemoglobin ≥9g/dL (≥90g/L) 14.2. Renal function: - Serum creatinine ≤1.5 x upper limit of normal (ULN) and calculated creatinine clearance more than 30ml/min 14.3. Liver function tests: - Total bilirubin ≤1.5 ULN - Alanine aminotransferase (ALT) ≤3 ULN. In the presence of liver metastases ALT ≤5 ULN. For patients in Cohort B, C and D: aspartate aminotransferase (AST) ≤3 ULN. In the presence of liver metastases AST ≤5 ULN. 15. 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: 15.1. Age >60 years 15.2. 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 15.3. 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. NB. Additional eligibility criteria apply for entry into each treatment cohort. |
| Participant exclusion criteria | 1. 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 2. 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 3. 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 4. 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 5. Major surgery (excluding minor procedures, e.g. placement of vascular access) within 4 weeks of the first dose of trial treatment 6. Pregnant or breastfeeding 7. Any condition that according to the treating physician may compromise the patient’s safety or the conduct of the trial 8. 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. NB. Additional eligibility criteria apply for entry into each treatment cohort |
| Recruitment start date | 15/12/2016 |
| Recruitment end date | 30/06/2019 |
Locations
Countries of recruitment
- England
- Scotland
- United Kingdom
- Wales
Study participating centres
The Royal Marsden Hospital
Fulham Road
Chelsea
London
SW3 6JJ
United Kingdom
Chelsea
London
SW3 6JJ
United Kingdom
The Royal Marsden Hospital
Downs Road
Sutton
SM2 5PT
United Kingdom
Sutton
SM2 5PT
United Kingdom
Western General Hospital
Crewe Road South
Edinburgh
EH4 2XU
United Kingdom
Edinburgh
EH4 2XU
United Kingdom
Addenbrooke's Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom
Cambridge
CB2 0QQ
United Kingdom
Beatson West of Scotland Cancer Centre
1053 Great Western Road
Glasgow
G12 0YN
United Kingdom
Glasgow
G12 0YN
United Kingdom
Bristol Haematology and Oncology Centre
Horfield Road
Avon
Bristol
BS2 8ED
United Kingdom
Avon
Bristol
BS2 8ED
United Kingdom
The Christie
550 Wilmslow Road
Withington
Manchester
M20 4BX
United Kingdom
Withington
Manchester
M20 4BX
United Kingdom
Clatterbridge Cancer Centre
Clatterbridge Health Park
Clatterbridge Road
Birkenhead
Wirral
CH63 4JY
United Kingdom
Clatterbridge Road
Birkenhead
Wirral
CH63 4JY
United Kingdom
Derriford Hospital
Derriford Road
Plymouth
PL6 8DH
United Kingdom
Plymouth
PL6 8DH
United Kingdom
Kent Oncology Centre
Maidstone Hospital
Hermitage Lane
Maidstone
ME16 9QQ
United Kingdom
Hermitage Lane
Maidstone
ME16 9QQ
United Kingdom
Royal Bournemouth Hospital
Castle Lane East
Bournemouth
BH7 7DW
United Kingdom
Bournemouth
BH7 7DW
United Kingdom
Royal Cornwall Hospital
2 Penventinnie Lane
Treliske
Truro
TR1 3LQ
United Kingdom
Treliske
Truro
TR1 3LQ
United Kingdom
Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom
Southampton
SO16 6YD
United Kingdom
St Barts Hospital
W Smithfield
London
EC1A 7BE
United Kingdom
London
EC1A 7BE
United Kingdom
University College Hospital
250 Euston Road
London
NW1 2PG
United Kingdom
London
NW1 2PG
United Kingdom
Velindre Hospital
Velindre Road
Whitchurch
Cardiff
CF14 2TL
United Kingdom
Whitchurch
Cardiff
CF14 2TL
United Kingdom
Weston Park Hospital
Whitham Road
Sheffield
S10 2SJ
United Kingdom
Sheffield
S10 2SJ
United Kingdom
Churchill Hospital
Old Road
Oxford
OX3 7LE
United Kingdom
Oxford
OX3 7LE
United Kingdom
Royal Devon and Exeter Hospital
Barrack Road
Exeter
EX2 5DW
United Kingdom
Exeter
EX2 5DW
United Kingdom
Sponsor information
Institute of Cancer Research
Research organisation
Research organisation
Royal Cancer Hospital
123 Old Brompton Road
London
SW7 3RP
England
United Kingdom
| Phone | +44 20 8722 4152 |
|---|---|
| plasmamatch-icrctsu@icr.ac.uk | |
| Website | http://www.icr.ac.uk/ |
"ROR" |
https://ror.org/043jzw605 |
Royal Marsden NHS Foundation Trust
Hospital/treatment centre
Hospital/treatment centre
Fulham Road
London
SW3 6JJ
England
United Kingdom
| Phone | +44 20 8722 4152 |
|---|---|
| plasmamatch-icrctsu@icr.ac.uk | |
| Website | http://www.royalmarsden.nhs.uk/pages/home.aspx |
|
"ROR" |
https://ror.org/0008wzh48 |
Funders
Funder type
Charity
Cancer Research UK
Private sector organisation / Other non-profit organizations
Private sector organisation / Other non-profit organizations
- Alternative name(s)
- CR_UK, Cancer Research UK - London, CRUK
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/12/2022 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | The main trial results for each treatment cohort will be published either separately or together in a peer-reviewed journal, on behalf of all collaborators. The results of the screening component, individual cohorts and translational research may be published together or individually. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study will be available upon request from plasmaMATCH-icrctsu@icr.ac.uk |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/10/2020 | 15/09/2020 | Yes | No |
| Results article | 23/04/2021 | 27/04/2021 | Yes | No | |
| Other publications | Commentary | 07/05/2022 | 20/01/2023 | Yes | No |
| HRA research summary | 28/06/2023 | No | No | ||
| Plain English results | 09/02/2024 | No | Yes |
Editorial Notes
09/02/2024: CRUK link to plain English results added.
20/01/2023: Publication reference added.
17/09/2021: Internal review.
27/04/2021: Publication reference added.
15/09/2020: Publication reference and total final enrolment number added.
28/03/2019: The condition has been changed from "Specialty: Cancer, Primary sub-specialty: Breast Cancer; UKCRC code/ Disease: Cancer/ Malignant neoplasm of breast" to "Breast cancer" following a request from the NIHR.
18/01/2019: The following changes have been made to the trial record:
1. Contact details have been changed
2. The ClinicalTrials.gov number has been added
3. The study hypothesis has been changed
4. Intervention "cohort E" was added
5. The participant inclusion criteria was changed
6. The participant exclusion criteria were changed to reflect the changes above
7. The planned sample size and target enrolment has changed from 1000 to 1150
8. The following sites have been removed as trial participating centres: Belfast City Hospital; Guy's Hospital; Charing Cross Hospital; Nottingham University Hospital; Queen Elizabeth Hospital Birmingham
9. John Radcliffe Hospital, Oxford was changed to Churchill Hospital, Oxford
11/08/2017: Cancer Help UK lay summary link added.
06/06/2017: Internal review.
19/12/2016: The recruitment start date has been updated from 12/12/2016 to 15/12/2016.
