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MRI and Early Decision-making in Chemotherapy for Breast Cancer

Completed
Conditions
Breast Neoplasms
Interventions
Other: magnetic resonance imaging
Registration Number
NCT02449824
Lead Sponsor
University of Leeds
Brief Summary

Firstly, the investigators aim to show that breast tumour blood flow, measured as part of a standard MRI examination, decreases at the earliest stage of neoadjuvant chemotherapy in those patients who go on to respond to treatment. Importantly, the investigators will also show that blood flow does not decrease in those patients who fail to respond.

Secondly, the investigators will test whether the decrease in tumour blood flow over the whole course of neoadjuvant chemotherapy can predict the response of the tumour measured at the time of surgery.

Detailed Description

i) Background. In a recent pilot study of 18 patients undergoing neoadjuvant chemotherapy (NAC), the investigators demonstrated for the first time that it was feasible to measure breast tumour blood flow (TBF) as part of a standard clinical MRI exam. TBF decreased dramatically in clinical responders and when compared with similar results obtained by others using \[15-O\] H2O positron emission tomography, the data led the investigators to hypothesise that TBF will decrease after only 1 cycle of NAC in responders. The data also suggested that changes in TBF over the course of NAC might predict pathological response.

ii) Aims. The primary aim is to assess response to first line NAC non-invasively after only 1 cycle of treatment. A secondary aim is to predict pathological response based upon changes measured over the course of NAC.

iii) Techniques and Methodology. The investigators will measure TBF using a novel MRI approach in 40 patients studied before, following 1 cycle, at the mid-point and the end of a fixed course of NAC. The MRI data will be compared with histological and molecular markers, obtained from biopsies at baseline and after 1 cycle of NAC and from specimens obtained during surgery at the end of NAC, to assess mechanisms of response to chemotherapy. In a sub-study of 10 patients imaged twice at baseline the investigators will assess the reproducibility of the TBF measures.

iv) Impact on breast cancer research. These techniques will provide absolute measures of tumour function during therapy which will particularly benefit non-responders to first line NAC allowing clear and objective decisions to be made about possible early changes in their treatment.

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
40
Inclusion Criteria
  • Newly diagnosed large but operable invasive carcinoma of the breast. All molecular subtypes are eligible and incidentally detected small volume metastatic disease is NOT an exclusion criterion.
  • Clinical indication for NAC as determined by the Breast Therapeutic MDT.
  • Sufficient biopsy material taken at diagnosis to measure the standard molecular markers.
  • Participant is willing and able to give informed consent for participation in the study.
  • Female, aged 18 years or above.
  • Histologically or cytologically confirmed invasive carcinoma of the breast and having received no prior treatment for this.
  • Female participants of child bearing potential must be willing to ensure that they or their partner use effective contraception during the study.
  • Participant has adequate renal function (estimated glomerular filtration rate ≥ 30 ml/min).
  • In the Investigator's opinion, is able and willing to comply with all study requirements.
Exclusion Criteria
  • Previous breast cancer treated with radiotherapy or chemotherapy or recurrent breast cancer.
  • Female participant who is pregnant, lactating or planning pregnancy during the course of the study.
  • Significant renal impairment (estimated glomerular filtration rate < 30 ml/min).
  • Contraindication to MRI.

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
magnetic resonance imagingmagnetic resonance imagingParticipants will undergo MRI at baseline, after 1 cycle, 3 cycles and at completion of neoadjuvant chemotherapy.
Primary Outcome Measures
NameTimeMethod
Change in tumour blood flow between baseline and after 1 cycle of neoadjuvant chemotherapy2 weeks

Cycle 1 length \~ 2 weeks.

Secondary Outcome Measures
NameTimeMethod
Tumour blood flow at baseline, after 1 cycle and after 6 cycles compared with molecular markers measured from biopsy data obtained at baseline and after 1 cycle and measured from surgical specimens taken after 6 cycles.~15 weeks

Cycles 1,2 \& 3 each of 2 weeks length. Cycles 4, 5 \& 6 each of 3 weeks length.

Rate of change in tumour blood flow measured at baseline, after 1 cycle, 3 cycles and 6 cycles of NAC & pathological response.~18 weeks

Cycles 1,2 \& 3 each of 2 weeks length. Cycles 4, 5 \& 6 each of 3 weeks length + short delay before surgery.

Within patient coefficient of variation in the measure of blood flow obtained at 2 baseline visits.2 weeks

Trial Locations

Locations (1)

Leeds Teaching Hospitals NHS Trust, St James's University Hospital

🇬🇧

Leeds, United Kingdom

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