Liquid Biopsies and Imaging in Breast Cancer (LIMA)

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Diagnostic test: Liquid biopsy; Diagnostic test: Multi-parametric MRI

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)

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Liselore M Janssen, MD; Phone Number: +31 (0) 6 25 77 71 94; Email: l.m.janssen-11@umcutrecht.nl
• Study Contact Backup: Name: Britt BM Suelmann, MD; Email: B.B.M.Suelmann@umcutrecht.nl

Study Locations

• Netherlands
  • Utrecht, Netherlands, 3584 CX
    • Universitair Medisch Centrum Utrecht

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Neoadjuvant systemic treatment; All patients undergo standard neoadjuvant treatment and additional multi-parametric MRI and liquid biopsies during neoadjuvant treatment.	Diagnostic test: Liquid biopsy; A blood sample containing circulating tumor DNA and circulating tumor cells.; Diagnostic test: Multi-parametric MRI; Multi-parametric MRI combines different imaging protocols in one session to measure more functional items than perfusion alone, addressing different aspects of tumor biology.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Residual Cancer Burden index in surgical resection specimen	The following parameters are required from pathologic examination in order to calculate Residual Cancer Burden (RCB) after neoadjuvant treatment: Primary tumor bed area, overall cancer cellularity (as percentage of area), percentage of cancer that is in situ disease, number of positive lymph nodes and diameter of largest metastasis. These parameters are filled in in the calculator that is available online to calculate the Residual Cancer Burden index: http://www3.mdanderson.org/app/medcalc/index.cfm?pagename=jsconvert3	After neoadjuvant treatment and surgery (approx. 6 months from diagnosis)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiological lesion volume on DCE MRI after NAC	Measured in three dimensions as described in ACR BI-RADS Atlas® 5th Edition	After neoadjuvant treatment (approx. 6 months from diagnosis)
pathological complete response, defined as ypT0/ypN0	Pathological complete response, defined as ypT0/ypN0	After neoadjuvant treatment and surgery (approx. 6 months from diagnosis)

Collaborators and Investigators

• Sponsor: UMC Utrecht
• Collaborators: Institut National de la Santé Et de la Recherche Médicale, France; Philips Electronics Nederland BV; Horizon 2020 - European Commission; Agena Bioscience GmbH; DiaDx; Stilla Technologies; ANGLE Europe Limited; ALS Automated Lab Solutions GmbH; Philips GmbH Innovate Technologies; Institut du Cancer de Montpellier
• Investigators: Principal Investigator: Kenneth GA Gilhuijs, PhD, UMC Utrecht

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2019
• Primary Completion (Actual): May 16, 2022
• Study Completion (Actual): May 16, 2022

Study Registration Dates

• First Submitted: December 20, 2019
• First Submitted That Met QC Criteria: January 8, 2020
• First Posted (Actual): January 10, 2020

Study Record Updates

• Last Update Posted (Actual): December 28, 2023
• Last Update Submitted That Met QC Criteria: December 21, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Breast Cancer; Magnetic resonance imaging; Neoadjuvant; Circulating Tumor DNA; Response Prediction; Liquid Biopsies
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 19-396

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Meta-data will be made publicly available. A steering committee will assess any request for reuse of the data.
• IPD Sharing Time Frame: Within 2 years after the LIMA Project has ended (and the LIMA breast cancer trial thus has been closed by the IRB)
• IPD Sharing Access Criteria: Any reasonable request compliant with patient consent will be granted.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No