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Personalised Disease Monitoring in Metastatic Breast Cancer (PDM-MBC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT04597580
Recruitment Status : Active, not recruiting
First Posted : October 22, 2020
Last Update Posted : August 28, 2023
Sahlgrenska University Hospital, Sweden
Information provided by (Responsible Party):
The Christie NHS Foundation Trust

Brief 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 '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 admitted 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.

Condition or disease
Breast Cancer Metastatic Estrogen Receptor-positive Breast Cancer

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

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Study Type : Observational
Actual Enrollment : 97 participants
Observational Model: Other
Time Perspective: Prospective
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
Actual Study Start Date : May 8, 2019
Estimated Primary Completion Date : May 31, 2026
Estimated Study Completion Date : January 31, 2030

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Primary Outcome Measures :
  1. 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 taht can be tested prospectively in future studies.

Secondary Outcome Measures :
  1. Best time for TK1 analysis during CDK4/6i treatment ("on treatment" vs "off treatment") [ Time Frame: 3-5 years ]
    The relative value of analysing TK1 "on CDK4/6i treatment" versus "off CDK4/6i treatment" for disease monitoring

  2. The economic impact of implementation of the chosen prediction model [ Time Frame: 3-5 years ]
    Cost effectiveness analysis of the using the prediction model

Biospecimen Retention:   Samples With DNA
Archived tumour tissue will be analysed using mutation panels to make personalised assays for circulating tumour DNA (dtDNA). ctDNA will be serially collected for subsequent analysis.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
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).

Inclusion Criteria:

  • Advanced breast cancer
  • ER-positive/HER2-negative
  • 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 therapy with an aromatase inhibitor and a CDK4/6 inhibitor
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2
  • Age ≥ 18 years
  • Life expectancy > 3 months
  • Radiologically assessable disease

Exclusion Criteria:

  • Known central nervous system (CNS) metastases, carcinomatous meningitis or leptomeningeal disease unless treated with radiotherapy and symptomatically stable at least 2 weeks after discontinuation of steroids
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04597580

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Department of Oncology, Sahlgrenska University Hospital
Gothenburg, Sweden
Department of Oncology, Ryhov Hospital
Jönköping, Sweden
Department of Oncology, Kalmar Hospital
Kalmar, Sweden
Department of Oncology, Linköping University Hospital
Linköping, Sweden
Department of Oncology, Södersjukhuset
Stockholm, Sweden
United Kingdom
The Christie NHS Foundation Trust
Manchester, United Kingdom, M20 4BX
Wigan Infirmary, Wrightington, Wigan and Leigh NHS Foundation Trust
Wigan, United Kingdom
Sponsors and Collaborators
The Christie NHS Foundation Trust
Sahlgrenska University Hospital, Sweden
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Principal Investigator: Dr Sacha Howell, MD, PhD University of Manchester and The Christie NHS Foundation Trust
Principal Investigator: Maria Ekholm, MD, PhD University of Gothenburg and Region Jönköping
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Responsible Party: The Christie NHS Foundation Trust Identifier: NCT04597580    
Other Study ID Numbers: CTFSp161
First Posted: October 22, 2020    Key Record Dates
Last Update Posted: August 28, 2023
Last Verified: August 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by The Christie NHS Foundation Trust:
Breast Neoplasms
Neoplasm Metastasis
Precision Medicine
disease monitoring
Biomarkers, Tumor
Circulating Tumor DNA
Thymidine Kinase
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases