The primary objective is to demonstrate proof of concept by exploring to what extent combinations of clinicipathological factors, multispectral magnetic resonance imaging (MRI), and liquid biopsies prior to, during and after completion of NAC, are…
ID
Source
Brief title
Condition
- Breast neoplasms malignant and unspecified (incl nipple)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary end point is Residual Breast Cancer Burden in surgical excision
specimen.
Secondary outcome
Secondary endpoints are radiological lesion volume on DCE MRI after NAC. In
addition, ypT0/ypN0 (i.e., absence of invasive cancer and in-situ cancer in the
breast and axillary nodes), ypT0/is ypN0 (i.e., absence of invasive cancer in
the breast and axillary nodes, irrespective of ductal carcinoma in situ), and
ypT0/is (i.e., absence of invasive cancer in the breast irrespective of ductal
carcinoma in situ or nodal involvement).
Background summary
It is currently impossible to predict which individual breast cancers will
respond sufficiently to chemotherapy and which will not. Neoadjuvant
chemotherapy (NAC) switches the order of the treatment: the chemotherapy is
given first - prior to surgery - allowing tumor response to be monitored while
the cancer is still in-situ. This treatment schedule also offers the
possibility to switch treatment upon demonstration of lack of response. Ideally
this should be done at the earliest signs of failure to treatment, to prevent
unnecessary exposure of patients to ineffective and often toxic chemotherapy.
Conversely, NAC may allow drug therapy to be stopped early when a complete
response has been achieved or if the disease becomes progressive. Anatomical
breast imaging is the standard method to assess response. However, it is well
known that in individual patients, changes in tumor size have limited efficacy
to predict the ultimate response after treatment. Whereas monitoring the
biological properties of the cancer using functional imaging may provide
complementary information, imaging can only visualize macroscopic disease.
Recent studies have suggested there is an inverse relation between the level of
circulating tumor cells and/or DNA fragments of tumor cells in the blood and
the response to chemotherapy, making this a potentially powerful tool in
predicting tumor response on a microscopic level, while also representing tumor
heterogeneity. We therefore hypothesize that a combination of known
clinicopathological factors, (functional) imaging and analysis of blood
(circulating tumor cells and tumor DNA) during NAC can reliably predict the
residual breast cancer burden after NAC in individual breast cancer patients.
Study objective
The primary objective is to demonstrate proof of concept by exploring to what
extent combinations of clinicipathological factors, multispectral magnetic
resonance imaging (MRI), and liquid biopsies prior to, during and after
completion of NAC, are able to forecast residual cancer burden after NAC in
addition to conventional clinical and pathological information.
Study design
Prospective observational cohort study
Study burden and risks
Patients in our study will undergo three MRI scans: before start of NAC,
halfway through and after completion of NAC. For some patients, this may mean
one additional MRI scan relative to routine clinical care, some patients would
undergo 3 MRI scans in routine clinical care. All patients will undergo a
PET/CT scan before the start of NAC. For a large portion of patients, this is
part of routine clinical care. For a subset, this will be for the purpose of
the study.
In addition, a blood draw of 30ml will be taken every first day of the
chemotherapy cycle. The blood draw will take place on a moment where a blood
draw or iv placement is planned, so the patients don*t have to undergo
additional venipuncture. The study entails no additional site visits, physical
examination, surveys or tests, apart from the before mentioned procedures.
Patients are expected to experience minimal burden and have negligible risk.
Allergic reaction to MRI contrast agent may occur in rare cases. Potential
benefits may be better staging by a PET/CT, and improved response evaluation by
an additional MRI.
Heidelberglaan 100
Utrecht 3584 CX
NL
Heidelberglaan 100
Utrecht 3584 CX
NL
Listed location countries
Age
Inclusion criteria
- Female patients aged 18 years or older
- 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
- ER-positive, HER2-negative, B&R grade 1 breast cancer
- Inflammatory breast cancer
- Distant metastases on PET/CT
- Ipsilateral breast cancer in history (contralateral breast cancer >5 years
ago is allowed)
- 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 contrastagent, and renal failure, defined by GFR < 30
mL/min/1.73m2.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL67308.041.19 |