Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Liquid Biopsies and Imaging in Breast Cancer (LIMA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04223492
Recruitment Status : Recruiting
First Posted : January 10, 2020
Last Update Posted : January 18, 2020
Sponsor:
Collaborators:
Horizon 2020 - European Commission
Philips Electronics Nederland BV
Agena Bioscience GmbH
DiaDx
Stilla Technologies
ANGLE Europe Limited
ALS Automated Lab Solutions GmbH
Institut National de la Santé Et de la Recherche Médicale, France
Philips GmbH Innovate Technologies
Institut du Cancer de Montpellier
Information provided by (Responsible Party):
Dr. Kenneth Gilhuijs, UMC Utrecht

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.

Condition or disease Intervention/treatment Phase
Breast Cancer Diagnostic Test: Liquid biopsy Diagnostic Test: Multi-parametric MRI Not Applicable

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)

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Liquid Biopsies and Imaging in Breast Cancer
Actual Study Start Date : January 2, 2019
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.




Primary Outcome Measures :
  1. Residual Cancer Burden index in surgical resection specimen [ Time Frame: After neoadjuvant treatment and surgery (approx. 6 months from diagnosis) ]
    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


Secondary Outcome Measures :
  1. Radiological lesion volume on DCE MRI after NAC [ Time Frame: After neoadjuvant treatment (approx. 6 months from diagnosis) ]
    Measured in three dimensions as described in ACR BI-RADS Atlas® 5th Edition

  2. pathological complete response, defined as ypT0/ypN0 [ Time Frame: After neoadjuvant treatment and surgery (approx. 6 months from diagnosis) ]
    Pathological complete response, defined as ypT0/ypN0



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04223492


Contacts
Layout table for location contacts
Contact: Liselore M Janssen, MD +31 (0) 6 25 77 71 94 l.m.janssen-11@umcutrecht.nl
Contact: Britt BM Suelmann, MD B.B.M.Suelmann@umcutrecht.nl

Locations
Layout table for location information
Netherlands
Universitair Medisch Centrum Utrecht Recruiting
Utrecht, Netherlands, 3584 CX
Contact: Liselore M Janssen, MD    +31 (0) 6 25 77 71 94    l.m.janssen-11@umcutrecht.nl   
Sponsors and Collaborators
UMC Utrecht
Horizon 2020 - European Commission
Philips Electronics Nederland BV
Agena Bioscience GmbH
DiaDx
Stilla Technologies
ANGLE Europe Limited
ALS Automated Lab Solutions GmbH
Institut National de la Santé Et de la Recherche Médicale, France
Philips GmbH Innovate Technologies
Institut du Cancer de Montpellier
Investigators
Layout table for investigator information
Principal Investigator: Kenneth GA Gilhuijs, PhD UMC Utrecht
Layout table for additonal information
Responsible Party: Dr. Kenneth Gilhuijs, Associate Professor, UMC Utrecht
ClinicalTrials.gov Identifier: NCT04223492    
Other Study ID Numbers: 19-396
First Posted: January 10, 2020    Key Record Dates
Last Update Posted: January 18, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Dr. Kenneth Gilhuijs, UMC Utrecht:
Breast Cancer
Neoadjuvant
Response Prediction
Liquid Biopsies
Magnetic resonance imaging
Circulating Tumor DNA
Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases