Clinical trial NCT03501394: What Factors Affect Breast Cancer Neoadjuvant Chemotherapy Efficacy?
Official title: What Are the Factors Affecting Neoadjuvant Chemotherapy Efficacy in Breast Cancer? A Non-invasive in Vivo Study Using Specialist Magnetic Resonance (MR) Methods
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Breast Neoplasm Malignant Breast Tissue
Keywords: Magnetic Resonance Imaging
Neoadjuvant Chemotherapy
Lead sponsor: University of Aberdeen
Sponsor class: OTHER
Collaborators: name: NHS Grampian
First posted: 2018-04-18
Enrollment: 25
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single group longitudinal study.
Primary purpose: BASIC_SCIENCE

Brief summary: Breast cancer is the most prevalent cancer affecting women. To treat locally advanced breast cancers, neoadjuvant chemotherapy (NACT) is often carried out before surgery to reduce the tumour size to allow breast conservation surgery. However, treatment response for individual patients varies, where the tumour may not respond to treatment and the quality of patient care is compromised if the NACT treatment plan is not optimised. Therefore, the assessment of NACT efficacy is beneficial for the early identification of these patients and appropriate management of treatment.

Breast tumours have unique features compared to healthy tissue, including abnormal tissue structure and biochemical composition. With NACT there are specific changes to such tumour features indicating tumour treatment response.

The purpose of this study is to establish how the changes to breast tumour features following NACT treatment are seen in non-invasive imaging. This study will look at scans of breast tumours using magnetic resonance imaging (MRI). Changes to tissue structure will be measured by advanced diffusion MRI techniques and changes to tumour related biochemical substances will be measured by advanced magnetic resonance spectroscopy techniques. The investigators aim to assess if these techniques can provide information on the tumour treatment response following subsequent rounds of NACT treatment.

In this longitudinal study, 25 patients undergoing NACT will be recruited for four repeated MRI investigations over the course of NACT treatment. Magnetic resonance (MR) measurements of tissue microstructure and biochemical composition will be compared against histological measurements and radiological assessments of treatment response.

The study will recruit patients undergoing treatment at the NHS Grampian. This research is funded by Friends of ANCHOR, Tenovus Scotland Grampian and the NHS Grampian Endowment Research Fund.

Detailed description: In this single group longitudinal study, the investigators propose that functional images from magnetic resonance (MR) methods performed at baseline and after 6 cycles of neoadjuvant chemotherapy (NACT) are in agreement with histological findings from pre-treatment biopsy and post-treatment surgically excised tissue. MR methods will be performed at baseline (pre-treatment) and after the 1st, 3rd and 6th (post-treatment) cycles of NACT treatment. The investigators hypothesise that specific physiological changes detected through MR methods are a manifestation of tumour response to NACT confirmed by histology and radiological assessment (Hypothesis 1). The investigators further hypothesise that early sensitivity to physiological changes manifesting from tumour response to NACT can be revealed by MR measurements after the first and third cycle of treatment (Hypothesis 2).

Research Question 1: Is there a difference in physiological parameters revealed by MR measurements at baseline and after completion of NACT?

Research Question 2: Do the physiological measurements at the completion of NACT from MR measures agree with histological findings?

Research Question 3: Is there a difference between MR measurements at baseline and after the first and third cycle of NACT?

Research Question 4: Is there a difference in MR measurements at baseline, first and third cycle of NACT, between positive treatment responders and non-responders.

MR measurements will be compared against clinical and study specific results from histological analysis and radiological assessment of MRI, mammography and ultrasound measures of tumour treatment response. Information collected from a health questionnaire will supplement interpretation of the data.

To test the effects of NACT on specific aspects of tumour physiology, paired t-tests will be performed on MR measures of lactate concentration, lipid composition and diffusion parameters, between baseline and post-treatment assessments (Research Question 1).

To examine the relationship between MR measurements and histology, correlation analysis will be conducted between baseline and post-treatment assessments. MR measures will be correlated against corresponding percentage changes in histological findings between biopsy and tumour excision (Research Question 2).

To evaluate MR measures as early markers of NACT efficacy, paired t-tests will be carried out between MR measures at pre-treatment and post 1st and 3rd cycles of NACT treatment (Research Question 3), with independent group difference determined between responders and non-responders (Research Question 4).

Eligibility criteria: Inclusion Criteria:

* Patients with pathologically confirmed invasive breast cancer undergoing neoadjuvant chemotherapy and surgery.

Exclusion Criteria:

* Condition to contradictive to MRI investigation with contrast agent (poor renal function, contrast agent allergy, metal implants or pace maker).
* Started hormone or chemotherapy treatment before recruitment.
* Undergoing treatment for concurrent cancer diagnosis.
* Marker coil contradictive to MRI investigation.

Primary outcomes:
measure: Baseline: Water diffusion probability density function (Full-Width-At-Half-Maximum, FWHM, units of micrometre)
timeFrame: Scan at pre-treatment baseline (Prior to start of Cycle 1, each cycle is 21 days)
measure: Post Cycle 1: Water diffusion probability density function (Full-Width-At-Half-Maximum, FWHM, units of micrometre)
timeFrame: Scan at the end of Cycle 1 (Each cycle is 21 days)
measure: Post Cycle 3: Water diffusion probability density function (Full-Width-At-Half-Maximum, FWHM, units of micrometre)
timeFrame: Scan at the end of Cycle 3 (Each cycle is 21 days)
measure: Post Treatment: Water diffusion probability density function (Full-Width-At-Half-Maximum, FWHM, units of micrometre)
timeFrame: Scan at the end of Cycle 6 (Each cycle is 21 days)
measure: Baseline: Water diffusivity (units of mm^2 /s)
timeFrame: Scan at pre-treatment baseline (Prior to start of Cycle 1, each cycle is 21 days)
measure: Post Cycle 1: Water diffusivity (units of mm^2 /s)
timeFrame: Scan at the end of Cycle 1 (Each cycle is 21 days)
measure: Post Cycle 3: Water diffusivity (units of mm^2 /s)
timeFrame: Scan at the end of Cycle 3 (Each cycle is 21 days)
measure: Post Treatment: Water diffusivity (units of mm^2 /s)
timeFrame: Scan at the end of Cycle 6 (Each cycle is 21 days)
measure: Baseline: Lactate Concentration (units of mM)
timeFrame: Scan at pre-treatment baseline (Prior to start of Cycle 1, each cycle is 21 days)
measure: Post Cycle 1: Lactate Concentration (units of mM)
timeFrame: Scan at the end of Cycle 1 (Each cycle is 21 days)
measure: Post Cycle 3: Lactate Concentration (units of mM)
timeFrame: Scan at the end of Cycle 3 (Each cycle is 21 days)
measure: Post Treatment: Lactate Concentration (units of mM)
timeFrame: Scan at the end of Cycle 6 (Each cycle is 21 days)
measure: Baseline: Lipid Peak Volume Ratio (Ratio Units)
timeFrame: Scan at pre-treatment baseline (Prior to start of Cycle 1, each cycle is 21 days)
measure: Post Cycle 1: Lipid Peak Volume Ratio (Ratio Units)
timeFrame: Scan at the end of Cycle 1 (Each cycle is 21 days)
measure: Post Cycle 3: Lipid Peak Volume Ratio (Ratio Units)
timeFrame: Scan at the end of Cycle 3 (Each cycle is 21 days)
measure: Post Treatment: Lipid Peak Volume Ratio (Ratio Units)
timeFrame: Scan at the end of Cycle 6 (Each cycle is 21 days)
measure: Baseline: Fat Fraction (units of %)
timeFrame: Scan at pre-treatment baseline (Prior to start of Cycle 1, each cycle is 21 days)
measure: Post Cycle 1: Fat Fraction (units of %)
timeFrame: Scan at the end of Cycle 1 (Each cycle is 21 days)
measure: Post Cycle 3: Fat Fraction (units of %)
timeFrame: Scan at the end of Cycle 3 (Each cycle is 21 days)
measure: Post Treatment: Fat Fraction (units of %)
timeFrame: Scan at the end of Cycle 6 (Each cycle is 21 days)
Secondary outcomes:
measure: Core Biopsy Tumour Tissue: Ki-67 Staining Percentage (units of %)
timeFrame: Pre-treatment baseline biopsy (Taken prior to start of Cycle 1, each cycle is 21 days). Assessed following completion of treatment cycles and the routine reporting of core biopsy and excised tissue samples.
measure: Excised Tumour Tissue: Ki-67 Staining Percentage (units of %)
timeFrame: Post-treatment surgery excision (Post Cycle 6, each cycle is 21 days). Assessed following the completion of routine pathological reporting of the excised tissue.
measure: Core Biopsy Tumour Tissue: Serotonin Staining Score (arbitrary units)
timeFrame: Pre-treatment baseline biopsy (Taken prior to start of Cycle 1, each cycle is 21 days). Assessed following completion of treatment cycles and the routine reporting of core biopsy and excised tissue samples.
measure: Excised Tumour Tissue: Serotonin Staining Score (arbitrary units)
timeFrame: Post-treatment surgery excision (Post Cycle 6, each cycle is 21 days). Assessed following the completion of routine pathological reporting of the excised tissue.
measure: Core Biopsy Tumour Tissue: Cellularity (units of %)
timeFrame: Pre-treatment baseline biopsy (Taken prior to start of Cycle 1, each cycle is 21 days). Assessed following completion of treatment cycles and the routine reporting of core biopsy and excised tissue samples.
measure: Excised Tumour Tissue: Cellularity (units of %)
timeFrame: Post-treatment surgery excision (Post Cycle 6, each cycle is 21 days). Assessed following the completion of routine pathological reporting of the excised tissue.
Other outcomes:
Locations:
city: Aberdeen
country: United Kingdom
facility: NHS Grampian
state: Aberdeenshire
Study officials:
affiliation: University of Aberdeen
name: Jiabao He, PhD
role: STUDY_CHAIR
affiliation: University of Aberdeen
name: Nicholas Senn, MPhys
role: PRINCIPAL_INVESTIGATOR
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