Personalised Disease Monitoring in Metastatic Breast Cancer

NCT04597580 | Active Not Recruiting DMC

• 1 other identifier: CTFSp161
• Study Type: observational
• Target: 97
• Locations: 2 countries
• Sites: 7

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 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.

Conditions

Breast Cancer Metastatic; Estrogen Receptor-positive Breast Cancer

Keywords

Breast Neoplasms; Neoplasm Metastasis; Precision Medicine; disease monitoring; Biomarkers, Tumor; Circulating Tumor DNA; Thymidine Kinase

Outcome Measures

Primary Outcomes (1)

• 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.

  3-5 years

Secondary Outcomes (1)

• Best time for TK1 analysis during CDK4/6i treatment ("on treatment" vs "off treatment")

  3-5 years

Other Outcomes (1)

• The economic impact of implementation of the chosen prediction model

  3-5 years

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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).

You may qualify if:

• 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).
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• The Christie NHS Foundation Trust: lead
• Sahlgrenska University Hospital: collaborator

Study Sites (7)

Department of Oncology, Sahlgrenska University Hospital

Gothenburg, Sweden

Location

Department of Oncology, Ryhov Hospital

Jönköping, Sweden

Location

Department of Oncology, Kalmar Hospital

Kalmar, Sweden

Location

Department of Oncology, Linköping University Hospital

Linköping, Sweden

Location

Department of Oncology, Södersjukhuset

Stockholm, Sweden

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Wigan Infirmary, Wrightington, Wigan and Leigh NHS Foundation Trust

Wigan, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 39692755 RESULT

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.

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis; Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2019
• First Posted: October 22, 2020
• Study Start: May 8, 2019
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): January 31, 2030
• Last Updated: December 2, 2025

Record last verified: 2025-11

Locations

GB (2); SE (5)