Personalised Disease Monitoring in Metastatic Breast Cancer

Breast Cancer Metastatic Clinical Trial

— PDM-MBC  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04597580
• Other study ID #: CTFSp161
• Status: Active, not recruiting
• Start date: May 8, 2019
• Est. completion date: January 31, 2030

Study information

• Verified date: August 2023
• Source: The Christie NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical 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 '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.

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 97
• Est. completion date: January 31, 2030
• Est. primary completion date: May 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer Metastatic
• Breast Neoplasms
• Estrogen Receptor-positive Breast Cancer

Locations

Country	Name	City	State
Sweden	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
United Kingdom	The Christie NHS Foundation Trust	Manchester
United Kingdom	Wigan Infirmary, Wrightington, Wigan and Leigh NHS Foundation Trust	Wigan

Sponsors (2)

Lead Sponsor	Collaborator
The Christie NHS Foundation Trust	Sahlgrenska University Hospital, Sweden

Countries where clinical trial is conducted

Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 taht can be tested prospectively in future studies.	3-5 years
Secondary	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	3-5 years
Secondary	The economic impact of implementation of the chosen prediction model	Cost effectiveness analysis of the using the prediction model	3-5 years