Breast Neoplasm Malignant Breast TissueNCT03501394
What Factors Affect Breast Cancer Neoadjuvant Chemotherapy Efficacy?
A study testing Magnetic Resonance Imaging, Histopathological Analysis and Health Questionnaire in people with Breast Neoplasm Malignant Breast Tissue, run by University of Aberdeen at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Neoplasm Malignant Breast Tissue
- What is being tested?
- Magnetic Resonance Imaging, Histopathological Analysis and Health Questionnaire
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 2 May 2018to Jun 2019
- 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
- Patients with pathologically confirmed invasive breast cancer undergoing neoadjuvant chemotherapy and surgery.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
NHS Grampian
Aberdeen, Aberdeenshire, AB25 2ZD
Nicholas Senn, MPhys, +44 (0)1224 43-8351, r03ns15@abdn.ac.uk
Nicholas Senn, MPhys
About this study
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
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.
Read more
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.
Read the 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).
- Conditions
- Breast Neoplasm Malignant Breast Tissue
- Being tested
- Magnetic Resonance Imaging, Histopathological Analysis, Health Questionnaire
- Keywords
- Magnetic Resonance Imaging, Neoadjuvant Chemotherapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Magnetic Resonance ImagingOther
Patients will undergo 4 MRI sessions during NACT treatment. The first scan will take place at treatment baseline before their first cycle of NACT treatment. The second scan will take place following the first treatment cycle prior to the second treatment cycle. Likewise, the third and last scan will take place after the third treatment cycle and sixth (final) treatment cycle prior to surgery. MRI scan sessions will be composed of research scans including diffusion and lipid profiling MR imaging methods and MR spectroscopy (MRS) methods.
Histopathological AnalysisOther
Study specific analysis will be performed on the core biopsy and tissue removed in surgery following the completion of NACT treatment. Standard routine histological analysis will be performed, as well as study specific analysis for immunostaining, grading and slide scan imaging for measurement of cellularity markers.
Health QuestionnaireOther
Health and demographic information will be collected.
| Study group | Role | What they receive |
|---|---|---|
| Single Arm | Experimental | 25 patients with pathologically confirmed invasive breast cancer who will undergo neoadjuvant chemotherapy treatment (NACT) and surgery will be recruited. During the study, patients will receive the standard care and the current study will not alter the care plan offered to them. All patients in the single arm will undergo 4 magnetic resonance imaging scan sessions. Histopathological analysis will be performed on the core biopsy and tumour tissue removed in surgery. Health questionnaire will be completed by each patient. Receives: Other: Magnetic Resonance Imaging; Other: Histopathological Analysis; Other: Health Questionnaire |
What is being measured
The primary outcome is the main question the study is designed to answer.
Baseline: Water diffusion probability density function (Full-Width-At-Half-Maximum, FWHM, units of micrometre)
The water diffusion probability density function will be quantified by the Full-Width-At-Half-Maximum with units of micrometre
Measured: Scan at pre-treatment baseline (Prior to start of Cycle 1, each cycle is 21 days)
Post Cycle 1: Water diffusion probability density function (Full-Width-At-Half-Maximum, FWHM, units of micrometre)
The water diffusion probability density function will be quantified by the Full-Width-At-Half-Maximum with units of micrometre
Measured: Scan at the end of Cycle 1 (Each cycle is 21 days)
Post Cycle 3: Water diffusion probability density function (Full-Width-At-Half-Maximum, FWHM, units of micrometre)
The water diffusion probability density function will be quantified by the Full-Width-At-Half-Maximum with units of micrometre
Measured: Scan at the end of Cycle 3 (Each cycle is 21 days)
Post Treatment: Water diffusion probability density function (Full-Width-At-Half-Maximum, FWHM, units of micrometre)
The water diffusion probability density function will be quantified by the Full-Width-At-Half-Maximum with units of micrometre
Measured: Scan at the end of Cycle 6 (Each cycle is 21 days)
Baseline: Water diffusivity (units of mm^2 /s)
Water diffusivity with units of mm^2 /s
Measured: Scan at pre-treatment baseline (Prior to start of Cycle 1, each cycle is 21 days)
Post Cycle 1: Water diffusivity (units of mm^2 /s)
Water diffusivity with units of mm^2 /s
Measured: Scan at the end of Cycle 1 (Each cycle is 21 days)
Post Cycle 3: Water diffusivity (units of mm^2 /s)
Water diffusivity with units of mm^2 /s
Measured: Scan at the end of Cycle 3 (Each cycle is 21 days)
Post Treatment: Water diffusivity (units of mm^2 /s)
Water diffusivity with units of mm^2 /s
Measured: Scan at the end of Cycle 6 (Each cycle is 21 days)
Baseline: Lactate Concentration (units of mM)
Lactate concentration with units of mM
Measured: Scan at pre-treatment baseline (Prior to start of Cycle 1, each cycle is 21 days)
Post Cycle 1: Lactate Concentration (units of mM)
Lactate concentration with units of mM
Measured: Scan at the end of Cycle 1 (Each cycle is 21 days)
Post Cycle 3: Lactate Concentration (units of mM)
Lactate concentration with units of mM
Measured: Scan at the end of Cycle 3 (Each cycle is 21 days)
Post Treatment: Lactate Concentration (units of mM)
Lactate concentration with units of mM
Measured: Scan at the end of Cycle 6 (Each cycle is 21 days)
Baseline: Lipid Peak Volume Ratio (Ratio Units)
Lipid peak volume ratio value with units of ratio
Measured: Scan at pre-treatment baseline (Prior to start of Cycle 1, each cycle is 21 days)
Post Cycle 1: Lipid Peak Volume Ratio (Ratio Units)
Lipid peak volume ratio value with units of ratio
Measured: Scan at the end of Cycle 1 (Each cycle is 21 days)
Post Cycle 3: Lipid Peak Volume Ratio (Ratio Units)
Lipid peak volume ratio value with units of ratio
Measured: Scan at the end of Cycle 3 (Each cycle is 21 days)
Post Treatment: Lipid Peak Volume Ratio (Ratio Units)
Lipid peak volume ratio value with units of ratio
Measured: Scan at the end of Cycle 6 (Each cycle is 21 days)
Baseline: Fat Fraction (units of %)
Fat Fraction with units of %
Measured: Scan at pre-treatment baseline (Prior to start of Cycle 1, each cycle is 21 days)
Post Cycle 1: Fat Fraction (units of %)
Fat Fraction with units of %
Measured: Scan at the end of Cycle 1 (Each cycle is 21 days)
Post Cycle 3: Fat Fraction (units of %)
Fat Fraction with units of %
Measured: Scan at the end of Cycle 3 (Each cycle is 21 days)
Post Treatment: Fat Fraction (units of %)
Fat Fraction with units of %
Measured: Scan at the end of Cycle 6 (Each cycle is 21 days)
Secondary outcomes (6)
Core Biopsy Tumour Tissue: Ki-67 Staining Percentage (units of %)
Ki-67 staining percentage with units of %, assessed on core biopsy tissue taken prior to start of treatment cycles.
Measured: 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.
Excised Tumour Tissue: Ki-67 Staining Percentage (units of %)
Ki-67 staining percentage with units of %, assessed on excised tissue taken from surgery following completion of treatment cycles.
Measured: Post-treatment surgery excision (Post Cycle 6, each cycle is 21 days). Assessed following the completion of routine pathological reporting of the excised tissue.
Core Biopsy Tumour Tissue: Serotonin Staining Score (arbitrary units)
Serotonin staining score with arbitrary units (multiplication of staining percentage and stain intensity scored 1 - 3), assessed on core biopsy tissue taken prior to start of treatment cycles.
Measured: 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.
Excised Tumour Tissue: Serotonin Staining Score (arbitrary units)
Serotonin staining score with arbitrary units (multiplication of staining percentage and stain intensity scored 1 - 3), assessed on excised tissue taken from surgery following completion of treatment cycles.
Measured: Post-treatment surgery excision (Post Cycle 6, each cycle is 21 days). Assessed following the completion of routine pathological reporting of the excised tissue.
Core Biopsy Tumour Tissue: Cellularity (units of %)
Cellularity with units of %, assessed on core biopsy taken prior to start of treatment cycles.
Measured: 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.
Excised Tumour Tissue: Cellularity (units of %)
Cellularity with units of %, assessed on excised tissue taken from surgery following completion of treatment cycles.
Measured: Post-treatment surgery excision (Post Cycle 6, each cycle is 21 days). Assessed following the completion of routine pathological reporting of the excised tissue.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2018
- Study start2 May 2018
- Primary completionJun 2019 (estimated)
- Study completionJun 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for Breast Neoplasm Malignant Breast TissueStudies of the same condition, open and under way.
- 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
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single group longitudinal study.
- Masking
- None (open label)
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Aberdeen
- Sponsor type
- University, hospital or other
- Collaborators
- NHS Grampian
- Responsible party
- Sponsor
- Investigators
- Jiabao He, PhD, Study chair, University of AberdeenNicholas Senn, MPhys, Principal investigator, University of Aberdeen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03501394
- Sponsor's protocol ID
- 2/108/7
- Other IDs
- 234794, 17/LO/1777
- Status last verified
- Apr 2018
- First submitted
- 28 Mar 2018
- Last updated
- 3 May 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Lee MC, Newman LA. Management of patients with locally advanced breast cancer. Surg Clin North Am. 2007 Apr;87(2):379-98, ix. doi: 10.1016/j.suc.2007.01.012.
PubMed 17498533Luangdilok S, Samarnthai N, Korphaisarn K. Association between Pathological Complete Response and Outcome Following Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer Patients. J Breast Cancer. 2014 Dec;17(4):376-85. doi: 10.4048/jbc.2014.17.4.376. Epub 2014 Dec 26.
PubMed 25548587Graham LJ, Shupe MP, Schneble EJ, Flynt FL, Clemenshaw MN, Kirkpatrick AD, Gallagher C, Nissan A, Henry L, Stojadinovic A, Peoples GE, Shumway NM. Current approaches and challenges in monitoring treatment responses in breast cancer. J Cancer. 2014 Jan 5;5(1):58-68. doi: 10.7150/jca.7047.
PubMed 24396498Danishad KK, Sharma U, Sah RG, Seenu V, Parshad R, Jagannathan NR. Assessment of therapeutic response of locally advanced breast cancer (LABC) patients undergoing neoadjuvant chemotherapy (NACT) monitored using sequential magnetic resonance spectroscopic imaging (MRSI). NMR Biomed. 2010 Apr;23(3):233-41. doi: 10.1002/nbm.1436.
PubMed 20175134Woodhams R, Kakita S, Hata H, Iwabuchi K, Kuranami M, Gautam S, Hatabu H, Kan S, Mountford C. Identification of residual breast carcinoma following neoadjuvant chemotherapy: diffusion-weighted imaging--comparison with contrast-enhanced MR imaging and pathologic findings. Radiology. 2010 Feb;254(2):357-66. doi: 10.1148/radiol.2542090405.
PubMed 20093508Walenta S, Mueller-Klieser WF. Lactate: mirror and motor of tumor malignancy. Semin Radiat Oncol. 2004 Jul;14(3):267-74. doi: 10.1016/j.semradonc.2004.04.004.
PubMed 15254870Carmona-Fontaine C, Bucci V, Akkari L, Deforet M, Joyce JA, Xavier JB. Emergence of spatial structure in the tumor microenvironment due to the Warburg effect. Proc Natl Acad Sci U S A. 2013 Nov 26;110(48):19402-7. doi: 10.1073/pnas.1311939110. Epub 2013 Nov 11.
PubMed 24218566Bolan PJ, Meisamy S, Baker EH, Lin J, Emory T, Nelson M, Everson LI, Yee D, Garwood M. In vivo quantification of choline compounds in the breast with 1H MR spectroscopy. Magn Reson Med. 2003 Dec;50(6):1134-43. doi: 10.1002/mrm.10654.
PubMed 14648561Baik HM, Su MY, Yu H, Mehta R, Nalcioglu O. Quantification of choline-containing compounds in malignant breast tumors by 1H MR spectroscopy using water as an internal reference at 1.5 T. MAGMA. 2006 May;19(2):96-104. doi: 10.1007/s10334-006-0032-4. Epub 2006 May 9.
PubMed 16779565He Q, Shkarin P, Hooley RJ, Lannin DR, Weinreb JC, Bossuyt VI. In vivo MR spectroscopic imaging of polyunsaturated fatty acids (PUFA) in healthy and cancerous breast tissues by selective multiple-quantum coherence transfer (Sel-MQC): a preliminary study. Magn Reson Med. 2007 Dec;58(6):1079-85. doi: 10.1002/mrm.21335.
PubMed 17969083Naressi A, Couturier C, Castang I, de Beer R, Graveron-Demilly D. Java-based graphical user interface for MRUI, a software package for quantitation of in vivo/medical magnetic resonance spectroscopy signals. Comput Biol Med. 2001 Jul;31(4):269-86. doi: 10.1016/s0010-4825(01)00006-3.
PubMed 11334636Yamada I, Hikishima K, Miyasaka N, Tokairin Y, Ito E, Kawano T, Kobayashi D, Eishi Y, Okano H. Esophageal carcinoma: Evaluation with q-space diffusion-weighted MR imaging ex vivo. Magn Reson Med. 2015 Jun;73(6):2262-73. doi: 10.1002/mrm.25334. Epub 2014 Jun 19.
PubMed 24947492Cheung SM, Wu WS, Senn N, Sharma R, McGoldrick T, Gagliardi T, Husain E, Masannat Y, He J. Towards detection of early response in neoadjuvant chemotherapy of breast cancer using Bayesian intravoxel incoherent motion. Front Oncol. 2023 Dec 6;13:1277556. doi: 10.3389/fonc.2023.1277556. eCollection 2023.
PubMed 38125950
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03501394
- Acronym / sponsor ID
- 2/108/7
- Conditions
- Breast Neoplasm Malignant Breast Tissue
- Keywords
- Magnetic Resonance Imaging, Neoadjuvant Chemotherapy
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- University of AberdeenUniversity, hospital or other
- Collaborators
- NHS Grampian
- Study start
- 2 May 2018 (actual)
- Primary completion
- Jun 2019 (estimated)
- Study completion
- Jun 2019 (estimated)
- First posted
- 18 Apr 2018 (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.
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).
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single group longitudinal study.
| Arm | Type | Receives |
|---|---|---|
| Single Arm | Experimental | Other: Magnetic Resonance Imaging, Other: Histopathological Analysis, Other: Health Questionnaire25 patients with pathologically confirmed invasive breast cancer who will undergo neoadjuvant chemotherapy treatment (NACT) and surgery will be recruited. During the study, patients will receive the standard care and the current study will not alter the care plan offered to them. All patients in the single arm will undergo 4 magnetic resonance imaging scan sessions. Histopathological analysis will be performed on the core biopsy and tumour tissue removed in surgery. Health questionnaire will be completed by each patient. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Patients with pathologically confirmed invasive breast cancer undergoing neoadjuvant chemotherapy and surgery.
Key exclusion criteria (4 listed)
- 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.
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 |
|---|---|---|
| Magnetic Resonance ImagingPatients will undergo 4 MRI sessions during NACT treatment. The first scan will take place at treatment baseline before their first cycle of NACT treatment. The second scan will take place following the first treatment cycle prior to the second treatment cycle. Likewise, the third and last scan will take place after the third treatment cycle and sixth (final) treatment cycle prior to surgery. MRI scan sessions will be composed of research scans including diffusion and lipid profiling MR imaging methods and MR spectroscopy (MRS) methods. | Other | Single Arm |
| Histopathological AnalysisStudy specific analysis will be performed on the core biopsy and tissue removed in surgery following the completion of NACT treatment. Standard routine histological analysis will be performed, as well as study specific analysis for immunostaining, grading and slide scan imaging for measurement of cellularity markers. | Other | Single Arm |
| Health QuestionnaireHealth and demographic information will be collected. | Other | Single Arm |
Primary outcome
Baseline: Water diffusion probability density function (Full-Width-At-Half-Maximum, FWHM, units of micrometre)
Time frame: Scan at pre-treatment baseline (Prior to start of Cycle 1, each cycle is 21 days)
The water diffusion probability density function will be quantified by the Full-Width-At-Half-Maximum with units of micrometre
Post Cycle 1: Water diffusion probability density function (Full-Width-At-Half-Maximum, FWHM, units of micrometre)
Time frame: Scan at the end of Cycle 1 (Each cycle is 21 days)
The water diffusion probability density function will be quantified by the Full-Width-At-Half-Maximum with units of micrometre
Post Cycle 3: Water diffusion probability density function (Full-Width-At-Half-Maximum, FWHM, units of micrometre)
Time frame: Scan at the end of Cycle 3 (Each cycle is 21 days)
The water diffusion probability density function will be quantified by the Full-Width-At-Half-Maximum with units of micrometre
Post Treatment: Water diffusion probability density function (Full-Width-At-Half-Maximum, FWHM, units of micrometre)
Time frame: Scan at the end of Cycle 6 (Each cycle is 21 days)
The water diffusion probability density function will be quantified by the Full-Width-At-Half-Maximum with units of micrometre
Baseline: Water diffusivity (units of mm^2 /s)
Time frame: Scan at pre-treatment baseline (Prior to start of Cycle 1, each cycle is 21 days)
Water diffusivity with units of mm^2 /s
Post Cycle 1: Water diffusivity (units of mm^2 /s)
Time frame: Scan at the end of Cycle 1 (Each cycle is 21 days)
Water diffusivity with units of mm^2 /s
Post Cycle 3: Water diffusivity (units of mm^2 /s)
Time frame: Scan at the end of Cycle 3 (Each cycle is 21 days)
Water diffusivity with units of mm^2 /s
Post Treatment: Water diffusivity (units of mm^2 /s)
Time frame: Scan at the end of Cycle 6 (Each cycle is 21 days)
Water diffusivity with units of mm^2 /s
Baseline: Lactate Concentration (units of mM)
Time frame: Scan at pre-treatment baseline (Prior to start of Cycle 1, each cycle is 21 days)
Lactate concentration with units of mM
Post Cycle 1: Lactate Concentration (units of mM)
Time frame: Scan at the end of Cycle 1 (Each cycle is 21 days)
Lactate concentration with units of mM
Post Cycle 3: Lactate Concentration (units of mM)
Time frame: Scan at the end of Cycle 3 (Each cycle is 21 days)
Lactate concentration with units of mM
Post Treatment: Lactate Concentration (units of mM)
Time frame: Scan at the end of Cycle 6 (Each cycle is 21 days)
Lactate concentration with units of mM
Baseline: Lipid Peak Volume Ratio (Ratio Units)
Time frame: Scan at pre-treatment baseline (Prior to start of Cycle 1, each cycle is 21 days)
Lipid peak volume ratio value with units of ratio
Post Cycle 1: Lipid Peak Volume Ratio (Ratio Units)
Time frame: Scan at the end of Cycle 1 (Each cycle is 21 days)
Lipid peak volume ratio value with units of ratio
Post Cycle 3: Lipid Peak Volume Ratio (Ratio Units)
Time frame: Scan at the end of Cycle 3 (Each cycle is 21 days)
Lipid peak volume ratio value with units of ratio
Post Treatment: Lipid Peak Volume Ratio (Ratio Units)
Time frame: Scan at the end of Cycle 6 (Each cycle is 21 days)
Lipid peak volume ratio value with units of ratio
Baseline: Fat Fraction (units of %)
Time frame: Scan at pre-treatment baseline (Prior to start of Cycle 1, each cycle is 21 days)
Fat Fraction with units of %
Post Cycle 1: Fat Fraction (units of %)
Time frame: Scan at the end of Cycle 1 (Each cycle is 21 days)
Fat Fraction with units of %
Post Cycle 3: Fat Fraction (units of %)
Time frame: Scan at the end of Cycle 3 (Each cycle is 21 days)
Fat Fraction with units of %
Post Treatment: Fat Fraction (units of %)
Time frame: Scan at the end of Cycle 6 (Each cycle is 21 days)
Fat Fraction with units of %
6 secondary outcomes
Core Biopsy Tumour Tissue: Ki-67 Staining Percentage (units of %)
Time frame: 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.
Excised Tumour Tissue: Ki-67 Staining Percentage (units of %)
Time frame: Post-treatment surgery excision (Post Cycle 6, each cycle is 21 days). Assessed following the completion of routine pathological reporting of the excised tissue.
Core Biopsy Tumour Tissue: Serotonin Staining Score (arbitrary units)
Time frame: 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.
Excised Tumour Tissue: Serotonin Staining Score (arbitrary units)
Time frame: Post-treatment surgery excision (Post Cycle 6, each cycle is 21 days). Assessed following the completion of routine pathological reporting of the excised tissue.
Core Biopsy Tumour Tissue: Cellularity (units of %)
Time frame: 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.
Excised Tumour Tissue: Cellularity (units of %)
Time frame: Post-treatment surgery excision (Post Cycle 6, each cycle is 21 days). Assessed following the completion of routine pathological reporting of the excised tissue.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2018.
- Background: PubMed 17498533Lee MC, Newman LA. Management of patients with locally advanced breast cancer. Surg Clin North Am. 2007 Apr;87(2):379-98, ix. doi: 10.1016/j.suc.2007.01.012.
- Background: PubMed 25548587Luangdilok S, Samarnthai N, Korphaisarn K. Association between Pathological Complete Response and Outcome Following Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer Patients. J Breast Cancer. 2014 Dec;17(4):376-85. doi: 10.4048/jbc.2014.17.4.376. Epub 2014 Dec 26.
- Background: PubMed 24396498Graham LJ, Shupe MP, Schneble EJ, Flynt FL, Clemenshaw MN, Kirkpatrick AD, Gallagher C, Nissan A, Henry L, Stojadinovic A, Peoples GE, Shumway NM. Current approaches and challenges in monitoring treatment responses in breast cancer. J Cancer. 2014 Jan 5;5(1):58-68. doi: 10.7150/jca.7047.
- Background: PubMed 20175134Danishad KK, Sharma U, Sah RG, Seenu V, Parshad R, Jagannathan NR. Assessment of therapeutic response of locally advanced breast cancer (LABC) patients undergoing neoadjuvant chemotherapy (NACT) monitored using sequential magnetic resonance spectroscopic imaging (MRSI). NMR Biomed. 2010 Apr;23(3):233-41. doi: 10.1002/nbm.1436.
- Background: PubMed 20093508Woodhams R, Kakita S, Hata H, Iwabuchi K, Kuranami M, Gautam S, Hatabu H, Kan S, Mountford C. Identification of residual breast carcinoma following neoadjuvant chemotherapy: diffusion-weighted imaging--comparison with contrast-enhanced MR imaging and pathologic findings. Radiology. 2010 Feb;254(2):357-66. doi: 10.1148/radiol.2542090405.
- Background: PubMed 15254870Walenta S, Mueller-Klieser WF. Lactate: mirror and motor of tumor malignancy. Semin Radiat Oncol. 2004 Jul;14(3):267-74. doi: 10.1016/j.semradonc.2004.04.004.
- Background: PubMed 24218566Carmona-Fontaine C, Bucci V, Akkari L, Deforet M, Joyce JA, Xavier JB. Emergence of spatial structure in the tumor microenvironment due to the Warburg effect. Proc Natl Acad Sci U S A. 2013 Nov 26;110(48):19402-7. doi: 10.1073/pnas.1311939110. Epub 2013 Nov 11.
- Background: PubMed 14648561Bolan PJ, Meisamy S, Baker EH, Lin J, Emory T, Nelson M, Everson LI, Yee D, Garwood M. In vivo quantification of choline compounds in the breast with 1H MR spectroscopy. Magn Reson Med. 2003 Dec;50(6):1134-43. doi: 10.1002/mrm.10654.
- Background: PubMed 16779565Baik HM, Su MY, Yu H, Mehta R, Nalcioglu O. Quantification of choline-containing compounds in malignant breast tumors by 1H MR spectroscopy using water as an internal reference at 1.5 T. MAGMA. 2006 May;19(2):96-104. doi: 10.1007/s10334-006-0032-4. Epub 2006 May 9.
- Background: PubMed 17969083He Q, Shkarin P, Hooley RJ, Lannin DR, Weinreb JC, Bossuyt VI. In vivo MR spectroscopic imaging of polyunsaturated fatty acids (PUFA) in healthy and cancerous breast tissues by selective multiple-quantum coherence transfer (Sel-MQC): a preliminary study. Magn Reson Med. 2007 Dec;58(6):1079-85. doi: 10.1002/mrm.21335.
- Background: PubMed 11334636Naressi A, Couturier C, Castang I, de Beer R, Graveron-Demilly D. Java-based graphical user interface for MRUI, a software package for quantitation of in vivo/medical magnetic resonance spectroscopy signals. Comput Biol Med. 2001 Jul;31(4):269-86. doi: 10.1016/s0010-4825(01)00006-3.
- Background: PubMed 24947492Yamada I, Hikishima K, Miyasaka N, Tokairin Y, Ito E, Kawano T, Kobayashi D, Eishi Y, Okano H. Esophageal carcinoma: Evaluation with q-space diffusion-weighted MR imaging ex vivo. Magn Reson Med. 2015 Jun;73(6):2262-73. doi: 10.1002/mrm.25334. Epub 2014 Jun 19.
- Individual participant dataSharing planned: No
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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.
Jiabao He, PhD study chair
University of Aberdeen
Nicholas Senn, MPhys principal investigator
University of Aberdeen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Magnetic Resonance Imaging, Histopathological Analysis and Health Questionnaire in people with Breast Neoplasm Malignant Breast Tissue, run by University of Aberdeen at 1 site in United Kingdom.
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 1 inclusion and 4 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: status not confirmed, as of the sponsor's last update on 3 May 2018. 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 United Kingdom. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Nicholas Senn, MPhys (+44 (0)1224 438351, r03ns15@abdn.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Baseline: Water diffusion probability density function (Full-Width-At-Half-Maximum, FWHM, units of micrometre) (time frame: Scan at pre-treatment baseline (Prior to start of Cycle 1, each cycle is 21 days)). The study lists 20 primary outcomes in all. 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 NCT03501394, which also lists 13 linked publications.
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 3 May 2018.