Clinical trial NCT04223492: Liquid Biopsies and Imaging in Breast Cancer
Official title: Liquid Biopsies and Imaging in Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Breast Cancer
Keywords: Breast Cancer
Neoadjuvant
Response Prediction
Liquid Biopsies
Magnetic resonance imaging
Circulating Tumor DNA
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
Collaborators: name: Horizon 2020 - European Commission
name: Philips Electronics Nederland BV
name: Agena Bioscience GmbH
name: DiaDx
name: Stilla Technologies
name: ANGLE Europe Limited
name: ALS Automated Lab Solutions GmbH
name: Institut National de la Santé Et de la Recherche Médicale, France
name: Philips GmbH Innovate Technologies
name: Institut du Cancer de Montpellier - Val d'Aurelle
First posted: 2020-01-10
Enrollment: 61
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: The aim of the study is to show proof of concept for combining multi-parametric MRI with liquid biopsies in addition to conventional clinical and pathologic information, to accurately predict response to neoadjuvant treatment for patients with primary breast cancer.

Detailed description: The response to neoadjuvant chemotherapy (NAC) in early stage breast cancer has important prognostic implications. Early, dynamic prediction of response allows for adaption of the treatment plan before completion, or even before the start of treatment. This strategy can help prevent overtreatment and related toxicity and correct for undertreatment with an ineffective regimen. The hypothesis of this study is that accurate dynamic response prediction may be reached by combining multi-parametric MRI with liquid biopsies prior to, during and after NAC, in addition to conventional clinical and pathological information. Magnetic resonance imaging (MRI) is non-invasive and is typically used for response evaluation in current clinical practice. It shows the size and perfusion of the tumor as they change during treatment. However, tumor size on MRI has limited predictive value for response to therapy. Multi-parametric MRI uses different imaging protocols in one session to measure more functional items than perfusion alone, addressing different aspects of tumor biology, and possibly improving predictive value. With this improvement, imaging still only visualizes macroscopic disease. Therefore, in the LIMA study, MRI will be combined with liquid biopsies containing circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA), which have both shown prognostic and predictive values in early stage breast cancer. Since the ctDNA may originate from cells in every part of the tumor, it may capture tumor heterogeneity. Liquid biopsies are minimally invasive and provide insight into microscopic tumor load and the tumor's genetic picture.

The aim of the study is to show proof of concept for combining multi-parametric MRI with liquid biopsies in addition to conventional clinical and pathologic information, to accurately predict response to neoadjuvant treatment for patients with primary breast cancer.

The LIMA is a multicenter prospective observational cohort study. Multi-parametric MRI will we performed prior to NAC, halfway and after completion of NAC. Liquid biopsies will be obtained before start of treatment, every 2 weeks during treatment and after completion of NAC. 100 patients will be enrolled in different hospitals.

Funding from the European Union Horizon 2020 research and innovation program under grant agreement no. 755333 (LIMA)

Eligibility criteria: Inclusion Criteria:

* Histologically proven invasive breast carcinoma
* Planned for neoadjuvant chemotherapy (and in case of a Her2-positive tumor: addition of trastuzumab and/or pertuzumab)

Exclusion Criteria:

* Luminal A breast cancer (defined as: ER-positive and HER2-negative by immunohistochemistry and Bloom and Richardson grade 1 or 2)
* Inflammatory breast cancer
* Distant metastases on PET/CT
* Other active malignant disease in the past 5 years (excluded squamous cell or basal cell carcinoma of the skin)
* Pregnant or lactating women
* Contra-indications for MRI according to standard hospital guidelines
* Contra-indications for gadolinium-based contrast-agent, including known prior allergic reaction to any contrast-agent, and renal failure, defined by GFR \< 30 mL/min/1.73m2

Primary outcomes:
measure: Residual Cancer Burden index in surgical resection specimen
timeFrame: After neoadjuvant treatment and surgery (approx. 6 months from diagnosis)
Secondary outcomes:
measure: Radiological lesion volume on DCE MRI after NAC
timeFrame: After neoadjuvant treatment (approx. 6 months from diagnosis)
measure: pathological complete response, defined as ypT0/ypN0
timeFrame: After neoadjuvant treatment and surgery (approx. 6 months from diagnosis)
Other outcomes:
Locations:
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht
Study officials:
affiliation: UMC Utrecht
name: Kenneth GA Gilhuijs, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Janssen LM, Suelmann BBM, Elias SG, Janse MHA, van Diest PJ, van der Wall E, Gilhuijs KGA. Improving prediction of response to neoadjuvant treatment in patients with breast cancer by combining liquid biopsies with multiparametric MRI: protocol of the LIMA study - a multicentre prospective observational cohort study. BMJ Open. 2022 Sep 20;12(9):e061334. doi: 10.1136/bmjopen-2022-061334.