PDM-MBC: Personalised Disease Monitoring in Metastatic Breast Cancer

Sponsor

The Christie NHS Foundation Trust (Other)

Overall Status

Recruiting

CT.gov ID

NCT04597580

Collaborator

Sahlgrenska University Hospital, Sweden (Other)

100

Enrollment

Locations

128.8

Anticipated Duration (Months)

14.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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	Intervention/Treatment	Phase
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

Study Design

Study Type:

Observational

Anticipated Enrollment :

100 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

Anticipated Primary Completion Date :

May 31, 2026

Anticipated Study Completion Date :

Jan 31, 2030

Outcome Measures

Primary Outcome Measures

Change in blood levels of ctDNA, CA15-3 and TK-1 assays from baseline to disease progression [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

Best time for TK1 analysis during CDK4/6i treatment ("on treatment" vs "off treatment") [3-5 years]
The relative value of analysing TK1 "on CDK4/6i treatment" versus "off CDK4/6i treatment" for disease monitoring
The economic impact of implementation of the chosen prediction model [3-5 years]
Cost effectiveness analysis of the using the prediction model

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Department of Oncology, Sahlgrenska University Hospital	Gothenburg	Sweden
2	Department of Oncology, Ryhov Hospital	Jönköping	Sweden
3	Department of Oncology, Kalmar Hospital	Kalmar	Sweden
4	Department of Oncology, Linköping University Hospital	Linköping	Sweden
5	Macclesfield District General Hospital, East Cheshire NHS Trust	Macclesfield	United Kingdom
6	The Christie NHS Foundation Trust	Manchester	United Kingdom	M20 4BX
7	Wigan Infirmary, Wrightington, Wigan and Leigh NHS Foundation Trust	Wigan	United Kingdom

Sponsors and Collaborators

The Christie NHS Foundation Trust
Sahlgrenska University Hospital, Sweden

Investigators

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