Breast Cancer MetastaticPDM-MBCNCT04597580
Personalised Disease Monitoring in Metastatic Breast Cancer
An observational study of Breast Cancer Metastatic and Estrogen Receptor-positive Breast Cancer, run by The Christie NHS Foundation Trust at 7 sites in 2 countries.
Trial summary
Patients with metastatic breast cancer may respond well to treatment and metastases can remain stable for several years. Despite personalised medicine being increasingly used for diagnosis and treatment, follow-up still include radiological response evaluation every 3-4 months, which renders a significant number of… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer Metastatic, Estrogen Receptor-positive Breast Cancer
- How many people
- 97 participants
- Where
- 7 sitesin 2 countries
- Study dates
- 8 May 2019to 31 Jan 2030
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with ER+/HER2- metastatic or locally advanced breast cancer, not amendable for curative surgery, eligible for 1st line endocrine therapy with aromatase inhibitor (AI) + CDK4/6-inhibitor (CDK4/6i).
Who may be able to join
- Confirmed metastatic breast cancer (stage 4) or locally advanced disease not amendable to curative resection. Patients who have locoregional disease only an in whom a response to therapy would lead to potentially curative resection are not eligible.
- ER+/HER2- breast cancer (assessed locally). NOTE: If immunohistochemical analysis is not available from metastatic tissue, the ER and HER2 status from the primary tumour should be used.
- For patients who have had a prior non-breast malignancy within the last 5 years (excluding in situ carcinoma of the cervix and basal cell carcinoma of the skin) biopsy of a metastatic site is required to confirm the diagnosis of metastatic ER+/HER2- breast cancer.
- Eligible for 1st line endocrine treatment with AI + CDK4/6-inhibitor according to local guidelines.
- NOTE: ≥ 12 month since termination of adjuvant AI if used NOTE: Patients may have received one prior line of chemotherapy for metastatic breast cancer but should have disease progression at study entry.
- Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-2 (Oken 1982).
Show all 11Show fewer
- Life expectancy >3 months.
- Age ≥ 18 years
- Metastatic disease must be radiologically assessable, by means of at least one of the following techniques: computerised tomography (CT) and/or magnetic resonance imaging (MRI), i.e. lesions can be measurable or non-measurable according to RECIST 1.1, but must be clearly evaluable according to the radiologist and/or treating physician. Patients with bone predominant disease who lack evaluable disease on CT according to RECIST 1.1.
- must have serial MRI including the representative area in addition to CT TAP. NOTE: Previously irradiated lesions are deemed measurable only if progression is documented at the site after completion of radiation.
- Willing and able to provide informed consent to undergo all trial procedures.
Who cannot join
- Known CNS metastases, carcinomatous meningitis or leptomeningeal disease unless treated with radiotherapy and symptomatically stable at least 2 weeks after discontinuation of steroids. For such patients, ongoing monitoring of CNS disease is required as standard of care. No screening is needed for asymptomatic patients.
- Concurrent disease(s) or familial, sociological or geographical condition that would, in the investigator's opinion, preclude compliance with study procedures.
- Any serious medical disorder that would compromise the patient's safety.
- Dementia altered mental status, or any psychiatric condition that would prevent the understanding or rendering of Informed Consent.
Trial locations and contacts
7 sites in 2 countries.
7 sites in 2 countries
Sweden5 sites
Department of Oncology, Sahlgrenska University Hospital
Gothenburg
Department of Oncology, Ryhov Hospital
Jönköping
Department of Oncology, Kalmar Hospital
Kalmar
Department of Oncology, Linköping University Hospital
Linköping
Department of Oncology, Södersjukhuset
Stockholm
United Kingdom2 sites
The Christie NHS Foundation Trust
Manchester, M20 4BX
Wigan Infirmary, Wrightington, Wigan and Leigh NHS Foundation Trust
Wigan
About this study
Official title: Personalised Disease Monitoring During Treatment With an Aromatase Inhibitor + Cyclin Dependent Kinase (CDK) 4/6 Inhibitor as 1st Line Endocrine Therapy in Patients With ER-positive/HER2-negative Metastatic Breast Cancer
Patients with metastatic breast cancer may respond well to treatment and metastases can remain stable for several years. Despite personalised medicine being increasingly used for diagnosis and treatment, follow-up still include radiological response evaluation every 3-4 months, which renders a significant number of 'unnecessary' exams for patients with long-term stable disease. Increasing evidence indicates that tumour markers such as circulating tumour DNA (ctDNA), thymidine kinase 1 (TK1) and cancer antigen 15-3 (CA15-3) may be useful for disease monitoring in the metastatic setting. However, algorithms that accurately define the time-points at which imaging can be foregone or reinstituted when progression is forecast, have not been developed. This study will measure ctDNA, TK1 and CA15-3 at all imaging time-points. The primary aim is to develop an algorithm based on these biomarkers, alone or in combination, that with sufficient specificity and sensitivity can advise whether a scan can be safely omitted at a specific time-point, for patients with MBC receiving first line therapy with AI plus cyclin dependent kinase 4/6 inhibitor (CDK4/6i). Additional samples will be stored such that novel biomarkers can also be tested in future. The cost-effectiveness of using the devised biomarker protocol will be evaluated.
Read the detailed description
One hundred patients with estrogen receptor positive (ER+)/ Human epidermal growth factor receptor negative (HER2-) metastatic or locally advanced breast cancer, eligible for 1st line endocrine therapy with AI + CDK4/6i will be included. Patients will receive standard therapy (AI + CDK4/6i) and follow-up will proceed according to local guidelines, namely cross sectional imaging with CT thorax/abdomen/pelvis +/- MRI as required and analysis of CA 15-3, every 3 cycles for the first year and every 3-4 cycles thereafter. Participation in the study will include serial blood sampling for the bespoke study biomarkers. Decisions on progression will be made according to the routine imaging tests and the biomarkers will be subsequently analysed.
The investigators hypothesise that the biomarkers ctDNA, TK1 and CA15-3, alone or in combination, will accurately correlate with disease status in patients receiving AI + CDK4/6i for metastatic breast cancer such that routine imaging can be delayed until predefined levels of biomarker progression.
Primary aim: To develop a biomarker-based prediction model to be used in patients with metastatic breast cancer, receiving first line therapy with AI and CDK4/6i, that provides the physician with a recommendation whether or not a radiological examination is required, based on the likelihood that the scan will actually show progressive disease.
Secondary aims
- To define the lead time between rising biomarker and subsequent progression on imaging
- To define the clinical utility of the bespoke biomarkers for disease monitoring
- The relative value of analysing TK1 "on CDK4/6i treatment" versus "off CDK4/6i treatment" for disease monitoring
- To define the economic impact of implementation of the chosen prediction model
- Keywords
- Breast Neoplasms, Neoplasm Metastasis, Precision Medicine, disease monitoring, Biomarkers, Tumor, Circulating Tumor DNA, Thymidine Kinase
- Medical subject headings
- Breast Neoplasms, Neoplasm Metastasis, Neoplasms
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in blood levels of ctDNA, CA15-3 and TK-1 assays from baseline to disease progression
ctDNA, CA15-3 and TK-1 assays will be performed at baseline, 2 weeks and at every imaging timepoint to develop a statistical algorithm to predict disease progression that can be tested prospectively in future studies.
Measured: 3-5 years
Secondary outcomes (1)
Best time for TK1 analysis during CDK4/6i treatment ("on treatment" vs "off treatment")
The relative value of analysing TK1 "on CDK4/6i treatment" versus "off CDK4/6i treatment" for disease monitoring
Measured: 3-5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2020
- Study start8 May 2019
- Primary completion31 May 2026 (estimated)
- Study completion31 Jan 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Breast Cancer MetastaticStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 97 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Christie NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Sahlgrenska University Hospital
- Responsible party
- Sponsor
- Investigators
- Dr Sacha Howell, MD, PhD, Principal investigator, University of Manchester and The Christie NHS Foundation TrustMaria Ekholm, MD, PhD, Principal investigator, University of Gothenburg and Region Jönköping
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04597580
- Sponsor's protocol ID
- CTFSp161
- Acronym
- PDM-MBC
- Status last verified
- Nov 2025
- First submitted
- 8 Jul 2019
- Last updated
- 2 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Mouhanna P, Stahlberg A, Andersson D, Albu-Kareem A, Elinder E, Eriksson O, Kavanagh A, Kovacs A, Larsson KF, Linderholm B, Uminska M, Osterlund T, Howell SJ, Ekholm M. Integration of personalised ultrasensitive ctDNA monitoring of patients with metastatic breast cancer to reduce imaging requirements. Int J Cancer. 2025 Apr 15;156(8):1509-1517. doi: 10.1002/ijc.35292. Epub 2024 Dec 18.
PubMed 39692755Brown NL, Howell SJ, Papantoniou D, Eriksson O, Bergqvist M, Williams A, Kavanagh A, Backlund A, Albu-Kareem A, Elinder E, Larsson K, Uminska M, Ekholm M. Prognostic performance of thymidine kinase 1 activity in patients with hormone receptor-positive and HER2-negative metastatic breast cancer treated with CDK4/6 and aromatase inhibitors. Breast Cancer Res Treat. 2026 Feb 11;216(1):6. doi: 10.1007/s10549-025-07879-0.
PubMed 41670750
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Personalised Disease Monitoring During Treatment With an Aromatase Inhibitor + Cyclin Dependent Kinase (CDK) 4/6 Inhibitor as 1st Line Endocrine Therapy in Patients With ER-positive/HER2-negative Metastatic Breast Cancer
- ClinicalTrials.gov ID
- NCT04597580
- Acronym / sponsor ID
- PDM-MBC / CTFSp161
- Keywords
- Breast Neoplasms, Neoplasm Metastasis, Precision Medicine, disease monitoring, Biomarkers, Tumor, Circulating Tumor DNA, Thymidine Kinase
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 97 participants (actual)
- Lead sponsor
- The Christie NHS Foundation TrustUniversity, hospital or other
- Collaborators
- Sahlgrenska University Hospital
- Study start
- 8 May 2019 (actual)
- Primary completion
- 31 May 2026 (estimated)
- Study completion
- 31 Jan 2030 (estimated)
- First posted
- 22 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Patients with metastatic breast cancer may respond well to treatment and metastases can remain stable for several years. Despite personalised medicine being increasingly used for diagnosis and treatment, follow-up still include radiological response evaluation every 3-4 months, which renders a significant number of 'unnecessary' exams for patients with long-term stable disease. Increasing evidence indicates that tumour markers such as circulating tumour DNA (ctDNA), thymidine kinase 1 (TK1) and cancer antigen 15-3 (CA15-3) may be useful for disease monitoring in the metastatic setting. However, algorithms that accurately define the time-points at which imaging can be foregone or reinstituted when progression is forecast, have not been developed. This study will measure ctDNA, TK1 and CA15-3 at all imaging time-points. The primary aim is to develop an algorithm based on these biomarkers, alone or in combination, that with sufficient specificity and sensitivity can advise whether a scan can be safely omitted at a specific time-point, for patients with MBC receiving first line therapy with AI plus cyclin dependent kinase 4/6 inhibitor (CDK4/6i). Additional samples will be stored such that novel biomarkers can also be tested in future. The cost-effectiveness of using the devised biomarker protocol will be evaluated.
Detailed description
One hundred patients with estrogen receptor positive (ER+)/ Human epidermal growth factor receptor negative (HER2-) metastatic or locally advanced breast cancer, eligible for 1st line endocrine therapy with AI + CDK4/6i will be included. Patients will receive standard therapy (AI + CDK4/6i) and follow-up will proceed according to local guidelines, namely cross sectional imaging with CT thorax/abdomen/pelvis +/- MRI as required and analysis of CA 15-3, every 3 cycles for the first year and every 3-4 cycles thereafter. Participation in the study will include serial blood sampling for the bespoke study biomarkers. Decisions on progression will be made according to the routine imaging tests and the biomarkers will be subsequently analysed.
The investigators hypothesise that the biomarkers ctDNA, TK1 and CA15-3, alone or in combination, will accurately correlate with disease status in patients receiving AI + CDK4/6i for metastatic breast cancer such that routine imaging can be delayed until predefined levels of biomarker progression.
Primary aim: To develop a biomarker-based prediction model to be used in patients with metastatic breast cancer, receiving first line therapy with AI and CDK4/6i, that provides the physician with a recommendation whether or not a radiological examination is required, based on the likelihood that the scan will actually show progressive disease.
Secondary aims
- To define the lead time between rising biomarker and subsequent progression on imaging
- To define the clinical utility of the bespoke biomarkers for disease monitoring
- The relative value of analysing TK1 "on CDK4/6i treatment" versus "off CDK4/6i treatment" for disease monitoring
- To define the economic impact of implementation of the chosen prediction model
Study design
- Observational model
- Other
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with ER+/HER2- metastatic or locally advanced breast cancer, not amendable for curative surgery, eligible for 1st line endocrine therapy with aromatase inhibitor (AI) + CDK4/6-inhibitor (CDK4/6i).
Key inclusion criteria (11 listed)
- Confirmed metastatic breast cancer (stage 4) or locally advanced disease not amendable to curative resection. Patients who have locoregional disease only an in whom a response to therapy would lead to potentially curative resection are not eligible.
- ER+/HER2- breast cancer (assessed locally). NOTE: If immunohistochemical analysis is not available from metastatic tissue, the ER and HER2 status from the primary tumour should be used.
- For patients who have had a prior non-breast malignancy within the last 5 years (excluding in situ carcinoma of the cervix and basal cell carcinoma of the skin) biopsy of a metastatic site is required to confirm the diagnosis of metastatic ER+/HER2- breast cancer.
- Eligible for 1st line endocrine treatment with AI + CDK4/6-inhibitor according to local guidelines.
- NOTE: ≥ 12 month since termination of adjuvant AI if used NOTE: Patients may have received one prior line of chemotherapy for metastatic breast cancer but should have disease progression at study entry.
Key exclusion criteria (4 listed)
- Known CNS metastases, carcinomatous meningitis or leptomeningeal disease unless treated with radiotherapy and symptomatically stable at least 2 weeks after discontinuation of steroids. For such patients, ongoing monitoring of CNS disease is required as standard of care. No screening is needed for asymptomatic patients.
- Concurrent disease(s) or familial, sociological or geographical condition that would, in the investigator's opinion, preclude compliance with study procedures.
- Any serious medical disorder that would compromise the patient's safety.
- Dementia altered mental status, or any psychiatric condition that would prevent the understanding or rendering of Informed Consent.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Change in blood levels of ctDNA, CA15-3 and TK-1 assays from baseline to disease progression
Time frame: 3-5 years
ctDNA, CA15-3 and TK-1 assays will be performed at baseline, 2 weeks and at every imaging timepoint to develop a statistical algorithm to predict disease progression that can be tested prospectively in future studies.
1 secondary outcome
Best time for TK1 analysis during CDK4/6i treatment ("on treatment" vs "off treatment")
Time frame: 3-5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2025.
- Results publication: PubMed 39692755Mouhanna P, Stahlberg A, Andersson D, Albu-Kareem A, Elinder E, Eriksson O, Kavanagh A, Kovacs A, Larsson KF, Linderholm B, Uminska M, Osterlund T, Howell SJ, Ekholm M. Integration of personalised ultrasensitive ctDNA monitoring of patients with metastatic breast cancer to reduce imaging requirements. Int J Cancer. 2025 Apr 15;156(8):1509-1517. doi: 10.1002/ijc.35292. Epub 2024 Dec 18.
- Derived from this study: PubMed 41670750Brown NL, Howell SJ, Papantoniou D, Eriksson O, Bergqvist M, Williams A, Kavanagh A, Backlund A, Albu-Kareem A, Elinder E, Larsson K, Uminska M, Ekholm M. Prognostic performance of thymidine kinase 1 activity in patients with hormone receptor-positive and HER2-negative metastatic breast cancer treated with CDK4/6 and aromatase inhibitors. Breast Cancer Res Treat. 2026 Feb 11;216(1):6. doi: 10.1007/s10549-025-07879-0.
- Individual participant dataSharing planned: Undecided
Related trials for Breast Cancer Metastatic
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruiting
Augmented-Reality ICG Fluorescence Second-Look for Residual Nodal Disease After Axillary Dissection in Breast Cancer
Breast Cancer, Breast Neoplasms
RecruitingPhase 2
BrAin Metastasis in tripLe Negateive Breast Cancer: IvoneScimab and Trop2 ADC
Triple-Negative Breast Cancer (TNBC), Brain Metastases
RecruitingPhase 1/2
A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Metastatic or Locally Advanced Breast Cancer
Metastatic Breast Cancer
RecruitingObservational study
Collection of CSF Samples From Participants With Metastatic Triple Negative Breast Cancer (TNBC) and HER2+ Breast Cancer With no Prior History Nor Active Radiographically Detectable Brain Metastases
Breast Cancer, Breast Carcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dr Sacha Howell, MD, PhD principal investigator
University of Manchester and The Christie NHS Foundation Trust
Maria Ekholm, MD, PhD principal investigator
University of Gothenburg and Region Jönköping
7 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Breast Cancer Metastatic and Estrogen Receptor-positive Breast Cancer, run by The Christie NHS Foundation Trust at 7 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 2 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Sweden, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in blood levels of ctDNA, CA15-3 and TK-1 assays from baseline to disease progression (time frame: 3-5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04597580, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Dec 2025.