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Liquid Biopsies and Imaging in Breast Cancer (LIMA)

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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

Tracking Information
First Submitted Date  ICMJE December 20, 2019
First Posted Date  ICMJE January 10, 2020
Last Update Posted Date January 18, 2020
Actual Study Start Date  ICMJE January 2, 2019
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 8, 2020)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 8, 2020)
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Liquid Biopsies and Imaging in Breast Cancer
Official Title  ICMJE Liquid Biopsies and Imaging in Breast Cancer
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)

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE Breast Cancer
Intervention  ICMJE
  • 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.
Study Arms  ICMJE Neoadjuvant systemic treatment
All patients undergo standard neoadjuvant treatment and additional multi-parametric MRI and liquid biopsies during neoadjuvant treatment.
Interventions:
  • Diagnostic Test: Liquid biopsy
  • Diagnostic Test: Multi-parametric MRI
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 8, 2020)
100
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
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
Listed Location Countries  ICMJE Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04223492
Other Study ID Numbers  ICMJE 19-396
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Responsible Party Dr. Kenneth Gilhuijs, UMC Utrecht
Study Sponsor  ICMJE UMC Utrecht
Collaborators  ICMJE
  • 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  ICMJE
Principal Investigator: Kenneth GA Gilhuijs, PhD UMC Utrecht
PRS Account UMC Utrecht
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP