Breast CancerLIMANCT04223492
Liquid Biopsies and Imaging in Breast Cancer
A study testing Liquid biopsy and Multi-parametric MRI in people with Breast Cancer, run by UMC Utrecht at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Liquid biopsy and Multi-parametric MRI
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 61 participants
- Where
- 1 siteNetherlands
- Study dates
- 2 Jan 2019to 16 May 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically proven invasive breast carcinoma
- Planned for neoadjuvant chemotherapy (and in case of a Her2-positive tumor: addition of trastuzumab and/or pertuzumab)
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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)
- Conditions
- Breast Cancer
- Being tested
- Liquid biopsy, Multi-parametric MRI
- Keywords
- Breast Cancer, Neoadjuvant, Response Prediction, Liquid Biopsies, Magnetic resonance imaging, Circulating Tumor DNA
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Liquid biopsyDiagnostic test
A blood sample containing circulating tumor DNA and circulating tumor cells.
Multi-parametric MRIDiagnostic test
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 group | Role | What they receive |
|---|---|---|
| Neoadjuvant systemic treatment | Other | All patients undergo standard neoadjuvant treatment and additional multi-parametric MRI and liquid biopsies during neoadjuvant treatment. Receives: Diagnostic Test: Liquid biopsy; Diagnostic Test: Multi-parametric MRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: After neoadjuvant treatment and surgery (approx. 6 months from diagnosis)
Secondary outcomes (2)
Radiological lesion volume on DCE MRI after NAC
Measured in three dimensions as described in ACR BI-RADS Atlas® 5th Edition
Measured: After neoadjuvant treatment (approx. 6 months from diagnosis)
pathological complete response, defined as ypT0/ypN0
Pathological complete response, defined as ypT0/ypN0
Measured: After neoadjuvant treatment and surgery (approx. 6 months from diagnosis)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jan 2020
- Study start2 Jan 2019
- Primary completion16 May 2022
- Study completion16 May 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by UMC UtrechtThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 61 participants (actual)
Sponsor and investigators
- Lead sponsor
- UMC Utrecht
- Sponsor type
- University, hospital or other
- 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 - Val d'Aurelle
- Responsible party
- Principal investigator, Dr. Kenneth Gilhuijs, UMC Utrecht
- Investigators
- Kenneth GA Gilhuijs, PhD, Principal investigator, UMC Utrecht
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04223492
- Sponsor's protocol ID
- 19-396
- Acronym
- LIMA
- Status last verified
- Dec 2023
- First submitted
- 20 Dec 2019
- Last updated
- 28 Dec 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Meta-data will be made publicly available. A steering committee will assess any request for reuse of the data.
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.
PubMed 36127090
Study at a glance
From the registry record, last updated by the sponsor on 28 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Liquid Biopsies and Imaging in Breast Cancer
- ClinicalTrials.gov ID
- NCT04223492
- Acronym / sponsor ID
- LIMA / 19-396
- Conditions
- Breast Cancer
- Keywords
- Breast Cancer, Neoadjuvant, Response Prediction, Liquid Biopsies, Magnetic resonance imaging, Circulating Tumor DNA
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 61 participants (actual)
- Lead sponsor
- UMC UtrechtUniversity, hospital or other
- 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 - Val d'Aurelle
- Study start
- 2 Jan 2019 (actual)
- Primary completion
- 16 May 2022 (actual)
- Study completion
- 16 May 2022 (actual)
- First posted
- 10 Jan 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Neoadjuvant systemic treatment | Other | Diagnostic Test: Liquid biopsy, Diagnostic Test: Multi-parametric MRIAll patients undergo standard neoadjuvant treatment and additional multi-parametric MRI and liquid biopsies during neoadjuvant treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Histologically proven invasive breast carcinoma
- Planned for neoadjuvant chemotherapy (and in case of a Her2-positive tumor: addition of trastuzumab and/or pertuzumab)
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Liquid biopsyA blood sample containing circulating tumor DNA and circulating tumor cells. | Diagnostic test | Neoadjuvant systemic treatment |
| Multi-parametric MRIMulti-parametric MRI combines different imaging protocols in one session to measure more functional items than perfusion alone, addressing different aspects of tumor biology. | Diagnostic test | Neoadjuvant systemic treatment |
Primary outcome
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
2 secondary outcomes
Radiological lesion volume on DCE MRI after NAC
Time frame: After neoadjuvant treatment (approx. 6 months from diagnosis)
pathological complete response, defined as ypT0/ypN0
Time frame: After neoadjuvant treatment and surgery (approx. 6 months from diagnosis)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Dec 2023.
- Derived from this study: PubMed 36127090Janssen 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.
- Individual participant dataSharing planned: Yes. Meta-data will be made publicly available. A steering committee will assess any request for reuse of the data.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kenneth GA Gilhuijs, PhD principal investigator
UMC Utrecht
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Liquid biopsy and Multi-parametric MRI in people with Breast Cancer, run by UMC Utrecht at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Residual Cancer Burden index in surgical resection specimen (time frame: After neoadjuvant treatment and surgery (approx. 6 months from diagnosis)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04223492, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Dec 2023.