Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

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.

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.

Magnetic Resonance Imaging

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.

Histopathological Analysis

Health and demographic information will be collected.

Health Questionnaire

Nicholas Senn, MPhys

Jiabao He, PhD

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.

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).

Single group with one arm and no masking.

What Factors Affect Breast Cancer Neoadjuvant Chemotherapy Efficacy?

What Are the Factors Affecting Neoadjuvant Chemotherapy Efficacy in Breast Cancer? A Non-invasive in Vivo Study Using Specialist Magnetic Resonance (MR) Methods

The water diffusion probability density function will be quantified by the Full-Width-At-Half-Maximum with units of micrometre

Lipid peak volume ratio value with units of ratio

Ki-67 staining percentage with units of %, assessed on core biopsy tissue taken prior to start of treatment cycles.

Ki-67 staining percentage with units of %, assessed on excised tissue taken from surgery following completion of treatment cycles.

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.

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.

Cellularity with units of %, assessed on core biopsy taken prior to start of treatment cycles.

Cellularity with units of %, assessed on excised tissue taken from surgery following completion of treatment cycles.

NHS Grampian

University of Aberdeen

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Lymphoma

Hodgkin Disease

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Hodgkin Lymphoma

All Drugs and Chemicals

Carbon Monoxide

Participants previously treated at St. Jude Children's Research Hospital with thoracic radiation therapy for Hodgkin lymphoma.

Interventions: Neurocognitive Evaluation, Quantitative Brain Imaging, Neurologic Evaluation, Comprehensive Health Questionnaire, Vascular Testing, Cardiopulmonary Exercise Testing, Echocardiography, Pulmonary Function Testing, Serum Biomarkers, and Ophthalmology Examination.

A group of healthy individuals matched for age, sex and race.

Interventions: Neurocognitive Evaluation, Quantitative Brain Imaging, Neurologic Evaluation, Comprehensive Health Questionnaire, Vascular Testing, Cardiopulmonary Exercise Testing, Echocardiography, Pulmonary Function Testing, Serum Biomarkers, and Ophthalmology Examination.

The neurocognitive evaluation will include measures of academic achievement, intelligence, sustained attention, memory, processing speed, executive functions, functional behavior, and emotional functioning.

Neurocognitive Evaluation

Imaging will include raw images to both quantify white matter hyperintensities and hemosiderin deposits, as well as cortical thickness and tissue segmentation. Brain imaging will be repeated on participants who are concurrently enrolled on BRIGHT and MIND protocols at St. Jude and who completed prior brain imaging during the BRIGHT clinic visit. The repeat MRI will be done at their 6 month MIND clinic visit.

Quantitative Brain Imaging

Evaluation includes a complete review of neurologic symptoms, and interview and examination by the neurologist, assessment of neurologic symptoms and determination of their impact on day-to-day living, and quantified neurologic examination by the neurologist.

Neurologic Evaluation

Participants will be asked to complete an approximately 450-item survey to assess health history and status, social and demographic factors, health behaviors, and psychosocial constructs.

Digital assessment of endothelial function will be studied, and central blood and pulse pressure and carotid-femoral pulse wave velocity will be non-invasively measured.

Vascular Testing

Study participants will undergo cardiopulmonary exercise testing by treadmill. Those participants whose physical performance does not permit walking safely on the treadmill (extreme deconditioning, lower extremity paralysis, balance disorder, acute lower extremity injury) will perform cardiopulmonary exercise testing on a bicycle or upper extremity ergometer using a comparable testing protocol.

Cardiopulmonary Exercise Testing

A complete 3D as well as 2D echocardiogram with Doppler and M-mode will be performed.

Echocardiography

Pulmonary function testing will include spirometry, lung volume measurements by body plethysmography, and single-breath carbon monoxide-diffusion capacity (DLCO).

Pulmonary Function Testing

Blood for serum biomarkers associated with cardiovascular morbidity will be drawn, including high-sensitivity C-reactive protein, serum homocysteine.

Serum Biomarkers

Ophthalmology examination will include a review of symptoms, examination, and fundus imaging. The examination will consist of visual acuity testing, refraction testing, retinoscopy, ocular pressure, and examination under mydriasis. Fundus photography will be used to capture an image of the retina for examination of potential hypertensive retinopathy.

Ophthalmology Examination

Kevin Krull, PhD

While thoracic radiation therapy (TRT) has been a primary component in successful treatment of a variety of childhood and adult cancers, the exposure to this treatment has been associated with significant cardiovascular and pulmonary morbidity in long-term survivors. Within non-cancer populations, cardiovascular and pulmonary morbidity is associated with increased risk for cerebral vascular accidents (CVAs), accelerated brain atrophy and neurocognitive impairment. Patients with chronic heart disease demonstrate problems with attention, processing speed, memory, and executive functions. Chronic pulmonary disease also increases the risk of stroke, leukoencephalopathy, and neurocognitive impairment in non-cancer populations. The investigators propose to examine indices of brain integrity, including neurocognitive performance and brain MRI/MRA, in long-term adult survivors of Hodgkin lymphoma (HL) treated with thoracic radiation and no direct central nervous system therapy.

OBJECTIVES:

1. To evaluate brain integrity in adult survivors of childhood HL treated with thoracic radiation therapy.
2. To identify therapeutic factors associated with brain integrity in adult survivors of childhood HL who are at risk for cardiac and pulmonary morbidity.
3. To examine associations between cardiac, vascular and pulmonary health and brain integrity in adult survivors of childhood HL treated with thoracic radiation.

This is an observational study to collect health data from long-term survivors of Hodgkin lymphoma (HL). Data will be collected once at participant enrollment. The long-term effects of thoracic radiation therapy (TRT) given earlier as part of the treatment for HL will be examined in long-term survivors and compared to health data collected from normal volunteers.

HL survivors who were treated at St. Jude Children's Research Hospital (SJCRH) with TRT will be recruited to complete a comprehensive neurocognitive evaluation, brain MRI/MRA, a clinical neurological exam, peripheral pulse contour analysis, non-invasive central blood pressure monitoring, cardiopulmonary exercise testing, and serum biomarkers related to cardiac disease. As part of their standard St. Jude LIFE protocol evaluation, they also complete an echocardiogram, pulmonary function tests and questionnaires designed to evaluate broad health, psychological, socioeconomic and environmental factors that impact everyday life.

A comparison sample of healthy individuals, frequency-matched on age, sex and race will also be recruited. The comparison group will complete the comprehensive neurocognitive evaluation, brain MRI/MRA, clinical neurological exam, pulse contour analysis, non-invasive central blood pressure monitoring, and cardiopulmonary exercise testing. Through the St. Jude LIFE protocol, the comparison sample will also complete an echocardiogram, pulmonary function tests and questionnaires designed to evaluate broad health, psychological, socioeconomic and environmental factors that impact everyday life.

Blood (5 ml) will be collected, frozen and stored for future serum biomarker assays.

Brain Integrity in Survivors of Hodgkin Lymphoma Treated With Thoracic Radiation

Brain Integrity in Survivors of Hodgkin Lymphoma (HL) Treated With Thoracic Radiation

To evaluate brain integrity in adult survivors of childhood cancer treated with thoracic radiation therapy.

Two-sided two-sample t test will be conducted to compare the difference of neurocognitive impairment in area of sustained attention and memory in the HL survivors and matched controls.

To evaluate brain integrity in adult survivors of childhood cancer treated with thoracic radiation therapy.

Two-sided two-sample proportional test will be used to compare the rates of leukoencephalopathy and hemosiderin deposits between in the HL survivors and matched controls.

To evaluate brain integrity in adult survivors of childhood cancer treated with thoracic radiation therapy.

Two-sided two-sample proportional test will be used to compare the rates of neurologic symptoms between the HL survivors and matched controls.

In HL survivors only, outcome variables will be: sustained attention (continuous), memory (continuous), leukoencephalopathy (dichotomous) and hemosiderin deposits (dichotomous). Independent variables are radiation dose to cardiopulmonary structures. Covariates will include chemotherapy exposures, particularly anthracycline exposure. For each continuous response variable, linear regression model will be used to see its association with these independent variables, adjusted for race/age/sex. Other possible covariates include educational attainment, employment and occupation, current physical activity, and alcohol and tobacco. For each dichotomous response variable, logistic regression model will be used to see its association with these independent variables, adjusted for race/age/sex. AIC criteria will be used to select the final model.

In HL survivors only, outcome variables will be: sustained attention (continuous), memory (continuous), leukoencephalopathy (dichotomous) and hemosiderin deposits (dichotomous). Independent variables are cardiac, vascular and pulmonary health. For each continuous response variable, linear regression model will be used to see its association with these independent variables, adjusted for race/age/sex. Other possible covariates include educational attainment, employment and occupation, current physical activity, and alcohol and tobacco. For each dichotomous response variable, logistic regression model will be used to see its association with these independent variables, adjusted for race/age/sex. AIC criteria will be used to select the final model.

National Cancer Institute (NCI)

St. Jude Children's Research Hospital

Nutritional and Metabolic Diseases

Digestive System Diseases

Anemia

Anemia, Iron-Deficiency

Iron Deficiencies

Gastrointestinal Stromal Tumors

Hematologic Diseases

Metabolic Diseases

Iron Metabolism Disorders

Anemia, Hypochromic

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Micronutrients

Mineral

Iron

Iron Supplement

Participants receive a Ferric Carboxymaltose injection by vein. Dose repeated 1 week later.

Health questionnaire completed at Baseline and at Weeks 4, 8, 12, and 24.

Participants take iron supplements by mouth every day for up to 3 months.

Health questionnaire completed at Baseline and at Weeks 4, 8, 12, and 24.

15 mg/kg by vein (up to 750 mg) over 15 min infusion. Dose repeated 1 week later.

Ferric Carboxymaltose

Participants take iron supplements by mouth every day for up to 3 months.

Iron Supplements

Health questionnaire completed at Baseline and at Weeks 4, 8, 12, and 24.

Questionnaire

Saroj Vadhan-Raj, MD

The goal of this clinical research study is to compare Injectafer® (ferric carboxymaltose) with an iron supplement to learn which may be more effective in improving red blood cell counts in patients who have iron-deficiency anemia (a low red blood cell count) because of a gastrointestinal stromal tumor (GIST) and/or systemic therapy.

The safety of ferric carboxymaltose will also be studied.

This is an investigational study. Ferric carboxymaltose is FDA approved and commercially available to treat iron deficiency anemia; however, it is considered investigational to use in patients who have cancer-related or systemic therapy-related anemia.

Up to 50 participants will take part in this study. All will be enrolled at MD Anderson.

Study Groups and Study Drug Administration:

If you are found to be eligible to take part in this study, you will be randomly assigned (as in the flip of a coin) to 1 of 2 study groups. This is done because no one knows if one group is better, the same, or worse than the other.

* If you are in Group A, you will receive ferric carboxymaltose injection by vein over about 15 minutes. You will receive 2 injections about 7 days apart (for example, on Days 0 \[the day you are assigned to a study group\] and 7).
* If you are in Group B, you will take iron supplements by mouth every day. This is considered standard of care for iron deficiency anemia and the study staff will discuss with you which iron supplements you will take and their risks.

You and the study staff will know to which group you are assigned.

Length of Study:

You may receive up to 2 injections of ferric carboxymaltose (if you are in Group A) or up to 3 months of oral iron supplements (if you are in Group B). You will no longer be able to take the study drug if intolerable side effects occur or if you are unable to follow study directions.

Your participation on the study will be over after you have completed the Week 24 visit.

Study Visits:

Baseline (within 1 week after you have been assigned to a study group):

* You will have a physical exam.
* You will complete a questionnaire about your health. It should take about 5 minutes to complete.
* Blood (about 1 tablespoon) will be drawn for routine tests and to test the level of iron in your blood.

One (1) time every week during Months 1-3, blood (about 1 tablespoon) will be drawn for routine tests.

At about Weeks 4, 8, 12, and 24 (the end-of-study visit):

* You will have a physical exam (Weeks 12 and 24 only).
* You will complete the same questionnaire you did at baseline.
* Blood (about 1 tablespoon) will be drawn for routine tests and to test the level of iron in your blood.

During Weeks 16 and 20, blood (less than 1 tablespoon) will be drawn to test the level of iron in your blood.

If you leave the study before Week 24, you will have the Week 24 study visits as soon as possible after you leave the study.

Efficacy of Ferric Carboxymaltose in Gastrointestinal Stromal Tumor (GIST) Patients With Iron Deficiency Anemia (IDA) Receiving Systemic Therapy

The primary endpoint is response (CR rate) in HGB within 3 months. Participant considered as to have a complete response (CR) if his/her HGB level increases \> 2 g/dL from baseline during 3 months following initiation of the study drug, and/or transfusion-dependent patient is transfusion free.

American Regent, Inc.

M.D. Anderson Cancer Center

Participants receive a Ferric Carboxymaltose injection by vein. Dose repeated 1 week later.

Health questionnaire completed at Baseline and at Weeks 4, 8, 12, and 24.

Ferric Carboxymaltose: 15 mg/kg by vein (up to 750 mg) over 15 min infusion. Dose repeated 1 week later.

Questionnaire: Health questionnaire completed at Baseline and at Weeks 4, 8, 12, and 24.

Group A - Ferric Carboxymaltose

Participants take iron supplements by mouth every day for up to 3 months.

Health questionnaire completed at Baseline and at Weeks 4, 8, 12, and 24.

Iron Supplements: Participants take iron supplements by mouth every day for up to 3 months.

Questionnaire: Health questionnaire completed at Baseline and at Weeks 4, 8, 12, and 24.

Group B - Iron Supplement

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Saroj Vadhan,Clinical Professor, Cytokine & Supportive Oncology

Due to early termination of the protocol and low accrual not enough data collected to analyze the Complete Response Rate in Hemoglobin.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
What Factors Affect Breast Cancer Neoadjuvant Chemotherapy Efficacy?	NCT03501394	Breast Neoplasm...	Magnetic Resona... Histopathologic... Health Question...	18 Years -	University of Aberdeen
Brain Integrity in Survivors of Hodgkin Lymphoma Treated With Thoracic Radiation	NCT01820117	Hodgkin Lymphom...	Neurocognitive ... Quantitative Br... Neurologic Eval... Health Question... Vascular Testin... Cardiopulmonary... Echocardiograph... Pulmonary Funct... Serum Biomarker... Ophthalmology E...	18 Years -	St. Jude Children's Research Hospital
Efficacy of Ferric Carboxymaltose in Gastrointestinal Stromal Tumor (GIST) Patients With Iron Deficiency Anemia (IDA) Receiving Systemic Therapy	NCT02949947	Malignant Neopl... Gastrointestina...	Ferric Carboxym... Iron Supplement... Questionnaire	18 Years -	M.D. Anderson Cancer Center

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