Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Hematinics

Anti-Infective Agents

Paclitaxel

Albumin-Bound Paclitaxel

Trastuzumab

Pertuzumab

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Liver Extracts

Tubulin Modulators

Antimitotic Agents

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Antineoplastic Agents, Immunological

Patients aged 18 to 40 in good physical condition Eastern Cooperative Oncology Group (ECOG) scale 0-1, who are set to receive neoadjuvant chemotherapy will be selected. Criteria for entry into the study include proper liver, kidney and bone marrow function as well as heart ejection fraction of ≥ 50%. Treatment will be carried out according to 4 x AC regimen (doxorubicin 60 mg/ m2 cyclophosphamide 600 mg/ m2 i.v. every 21 or every 14 days + pegfilgastrim) followed by 12 x paclitaxel 80 mg/ m2 every 7 days and in the case of HER2 positive tumors trastuzumab ± pertuzumab (according to SPC).

The group in which, concurrently with chemotherapy,IPA will be ordered, by means of supervised high intensity interval training twice a week.

During the course of chemotherapy, the intensity of physical activity will be increasing.

HIIT training twice a week throughout the chemotherapy: treadmill, elliptical, stationary bicycle and indoor rower. The intensity of physical activity will be increasing during consecutive mesocycles. Each training session will begin with a 10-min. wole-body warm-up session at 50-60% hear rate (HR) max. Mesocycle 1 - one month with 4 sets of 1 min. 45 sec. of exercise at a maximal intensity of 75% HR max. Mesocycle 2 with exercises at 80% to 90% HR max divided into 3 periods: 1/ one month, session of 5 sets 1 min. 30 sec. each; 2/ two months, sessions of 5 sets 1 min. 45 sec. each; 3/ two months, sessions of 5 sets 2 min. each. Moreover patients will be instructed to individually perform- a 45-min. aerobic training session (e.g.: walking, jogging, roller skating, swimming) once a week, in patient's own time.

High Intensity Interval Training (HIIT)

Patients aged 18 to 40 in good physical condition (Eastern Cooperative Oncology Group (ECOG) scale 0-1) who are set to receive neoadjuvant chemotherapy will be selected. Criteria for entry into the study include proper liver, kidney and bone marrow function as well as heart ejection fraction of ≥ 50%. Treatment will be carried out according to 4 x AC regimen (doxorubicin 60 mg/ m2 cyclophosphamide 600 mg/ m2 i.v. every 21 or every 14 days + pegfilgastrim) followed by 12 x paclitaxel 80 mg/ m2 every 7 days and in the case of HER2 positive tumors trastuzumab ± pertuzumab (according to SPC).

neoadjuvant treatment (doxorubicin, cyclophosphamide, paclitaxel, trastuzumab, pertuzumab)

Patients will be asked to perform 150-300 min. of moderate-intensity aerobic activity or 75-150 min. of vigorous aerobic activity. Each participant will be monitored by an activity watch worn at all times by the patient.

Standard Supportive Care

Maria Litwiniuk, Prof

Joanna Kufel-Grabowska, MD, PhD

Maciej Górecki, PT, PhD

The main goal of this study is to assess the impact of supervised intense physical activity (IPA) on outcomes of neoadjuvant chemotherapy in young women with breast cancer (YWBC). In this project standard neoadjuvant chemotherapy will be used concordant with summary of product characteristics (SPC). However during treatment (including days of chemotherapy application) an additional modifier of therapy will be carried out in the form of intense physical activity. This strategy is not recognized in SPC. This project aims to improve the results of breast cancer treatment in young women. According to available data, nowadays this subset of breast cancer patients has worse therapy results in comparison to older women. This is partially because of the different tumor characteristics; young women are more likely to present with human epithelial growth factor receptor 2 (HER2) receptor overexpression or with triple negative breast cancer. In the treatment of YWBC, preoperative chemotherapy is most often the first step. This enables the opportunity to assess the effectiveness of additional interventions in a mode it was never tested before. It is believed that physical activity improves the results of breast cancer treatment, however there are only few reports describing its benefit and role in terms of preoperative chemotherapy.

In the current project, the investigators planned to introduce supervised increased physical activity concurrently with neoadjuvant treatment in YWBC at early stage of disease. The main goal of the study is to assess the effect of physical activity on preoperative chemotherapy outcomes. The change of tumor size after neoadjuvant chemotherapy, as well as the impact on Quality of Life (QoL) and Patients' Reported Outcome (PRO) in described above treatment modality. Secondary endpoints are the following: the pathologic Complete Response (pCR), disease free survival after 3 years (3-yr DFS), overall survival (OS), cardiotoxicity of treatment, the effect of physical activity on tumor microenvironment and Ki67 as well as the impact of increased physical activity on further patients' lifestyle changes.

The main goal of this study is to assess the impact of supervised intense physical activity (IPA) on outcomes of neoadjuvant chemotherapy in young women with breast cancer (YWBC). In this project standard neoadjuvant chemotherapy will be used concordant with summary of product characteristics (SPC). However during treatment (including days of chemotherapy application) an additional modifier of therapy will be carried out in the form of intense physical activity. This strategy is not recognized in SPC. This project aims to improve the results of breast cancer treatment in young women. According to available data, nowadays this subset of breast cancer patients has worse therapy results in comparison to older women. This is partially because of the different tumor characteristics; young women are more likely to present with human epithelial growth factor receptor 2 (HER2) receptor overexpression or with triple negative breast cancer. In the treatment of YWBC preoperative chemotherapy is most often the first step. This enables the opportunity to assess the effectiveness of additional interventions in a mode it was never tested before. It is believed that physical activity improves the results of breast cancer treatment, however there are only few reports describing its benefit and role in terms of preoperative chemotherapy.

In the current project the investigators planned to introduce supervised increased physical activity concurrently with neoadjuvant treatment in YWBC at early stage of disease. The main goal of the study is to assess the effect of physical activity on preoperative chemotherapy outcomes. The change of tumor size after neoadjuvant chemotherapy, as well as the impact on Quality of Life (QoL) and Patients' Reported Outcome (PRO) in described above treatment modality. Secondary endpoints are the following: the pathologic Complete Response (pCR), disease free survival after 3 years (3-yr DFS), overall survival (OS), cardiotoxicity of treatment, the effect of physical activity on tumor microenvironment and Ki67 as well as the impact of increased physical activity on further patients' lifestyle changes. Patients aged 18 to 40 in good physical condition Eastern Cooperative Oncology Group (ECOG) 0-1 who are set to receive neoadjuvant chemotherapy will be selected. Criteria for entry into the study include proper liver, kidney, and bone marrow function as well as heart ejection fraction ≥ 50%. Treatment will be carried out according to 4 x AC regimen (doxorubicin 60 mg/ m2 cyclophosphamide 600 mg/ m2 i.v. every 21 or every 14 days + pegfilgastrim) followed by 12 x paclitaxel 80 mg/ m2 every 7 days and in the case of HER2 positive tumors trastuzumab ± pertuzumab (according to SPC).

After receiving patients' agreement and signing informed consent form, the patient will undergo testing by a multidisciplinary panel of physicians. A cardiological assessment will be completed along with spiroergometry, bone density and anthropometric measurements. The patient will be asked to complete surveys assessing their QoL together with reporting their previous activity level and everyday functioning. Patients will be randomized into two groups - the comparator group undergoing chemotherapy and the intervention group in which additional intervention IPA will be ordered, in means of supervised high intensity interval training twice a week. Modalities of exercise will include: treadmill, elliptical, stationary bicycle and indoor rower. During the course of chemotherapy, the intensity of physical activity will be increasing. Moreover, throughout the entire therapy time, a 45-minute aerobic training session (e.g.: walk, jogging, roller skates, swimming) will be introduced once a week. In the control group, patients will be asked to independently perform their physical activity at an intensity and volume specified in general guidelines: 150-300 min. of moderate-intensity aerobic activity or 75-150 min. of vigorous aerobic activity. Each participant will be monitored at all times by the use of a standard biologic activity recording device.

After the administration of anthracycline, the following procedures will be done: tumor/tumor bed core needle biopsy, mammography, breast ultrasound and cardiological assessment. Following the completion of chemotherapy all testing will be repeated with the exception of bone density measurement and core biopsy. These tests will be repeated one year after surgery. In addition, patients will be assessed for their immune status before and after chemotherapy, as well as one year of observation. When tissue material is available an assessment of the composition of inflammatory infiltrate will be performed using immunohistochemical stainings for immune cell markers. The investigators also planned to preserve material taken from the primary tumor and possible metastasis for molecular analysis (next generation sequencing (NGS), microarrays). The observation will be carried out for 10 years with own resources.

Patients will be randomized into two groups. Patients which are set to receive neoadjuvant chemotherapy will be selected. Treatment will be carried out according to 4 x AC regimen (doxorubicin 60 mg/ m2 cyclophosphamide 600 mg/ m2 i.v. every 21 or every 14 days + pegfilgastrim) followed by 12 x paclitaxel 80 mg/ m2 every 7 days and in the case of HER2 positive tumors trastuzumab ± pertuzumab (according to SPC).

The group in which additional intervention IPA will be ordered, in means of supervised high intensity interval training twice a week. During the course of chemotherapy, the intensity of physical activity will be increasing. Moreover, throughout the entire therapy time, there will be introduced a 45-minute aerobic training session (e.g.: walk, jogging, roller skates, swimming) ones a week. In the control group patients will be asked to independently continue their regular physical activity same as prior to the oncologic treatment.

Supervised Physical Activity in Young Women With Early Breast Cancer During Neoadjuvant Chemotherpy

Score based on the QLQ-BR23 questionnaire which includes the following scales: body image (score range 4-16), sexual functioning (score range 2-8), systemic therapy side effects (score range 7-28), breast symptoms (score range 4-16), arm symptoms (score range 3-12), sexual enjoyment (score range 1-4), future perspectives (score range 1-4), being upset by hair loss (score range 1-4); higher score meaning worse outcome (higher level of symptomatology or lower level of functioning).

complete pathological response (pCR, pathologic Complete Response)

A change in LVEF \>10 percentage points, to a value below 50%.

For patients with acute onset dyspnea increase \<100 pg/ml, for patients with slow increase in breathlessness increase \>35 pg/ml.

Daily number of steps measured throughout the intervention using an activity watch.

Measured during physical activity using an activity watch.

Measured throughout the intervention using an activity watch.

Daily number of minutes spent actively measured using an activity watch.

Daily number of minutes of sleep measured using an activity watch.

Score based on Acceptance of Illness Scale, a single scale with range of points 8-40, with a higher score meaning better acceptance of one's medical condition.

Assessment of the percentage of immune cells infiltrating the tumor based on immunohistochemical staining of paraffin sections of a tumor. Staining will include the following markers: CD45, CD8, CD4 to assess absolute inflammatory cells, cytotoxic T cells, and helper T cells. The infiltrating cells will be measured as an area occupied by inflammatory cells over total area, and will be expressed as a percentage.

Ki67 will be assessed based on immunohistochemical staining of paraffine section of a tumor. Ki67 index will be measured as a number of ki67-positive cells over the total number of invasive cells, and will be expressed as a percentage.

The Greater Poland Cancer Centre

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

Symptoms and General Pathology

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Dilatation, Pathologic

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Proteasome Inhibitors

Measurement of the change in the vasodilatative reserve of the brachial artery

Flow mediated dilation

Matthias Totzeck

Lena Hinrichs

Treatment options for multiple myeloma have increased significantly over the last years with the approval of immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs). These therapies have markedly improved overall survival for these patients to a median of 5-7 years. Due to the advanced age, the myeloma patient collective has a high prevalence of pre-existing cardiovascular comorbidities. In addition, the primary disease process contributes to cardiovascular complications. With the beginning of anti-tumor therapy, an increased incidence of cardiovascular complications in myeloma patients can be determined. This includes hypertension, left ventricular dysfunction, heart failure and both arterial and venous thromboembolic events. The detailed mechanism by which proteasome inhibitors and immunomodulatory agents lead to increased cardiovascular events is not established at this time. Endothelial dysfunction, as a possible mechanism of cardiovascular toxicity, is difficult to assess. Flow-mediated dilation (FMD) is an noninvasive method to measure endothelial function by assessing the change in the vasodilatative reserve of the brachial artery. Several independent recent investigations implicate that vascular (endothelial) dysfunction precedes hypertension and heart failure. This has been related to a reduced level of metabolites of the l-arginine-nitric oxide (NO) signaling pathway.

Hypothesis:

1. Anti-myeloma therapy exert vascular toxicity by limiting endothelial function. Endothelial function, assessed by the change in the vasodilatative reserve of the brachial artery (flow-mediated dilation = FMD) decreases after myeloma therapy.
2. Patients with multiple myeloma have a limited endothelial function compared to a healthy control group.

A total of 40 myeloma patients will be examined. Measurements will be taken at baseline, 1 month and 6 month after myeloma therapy. Patients should not have received chemotherapy for at least 3 months. Furthermore a healthy sex- and age-matched control group will be examined.

Treatment options for multiple myeloma have increased significantly over the last years with the approval of immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs). These therapies have markedly improved overall survival for these patients to a median of 5-7 years, many continue to live for more than 10 years. Due to the advanced age, the myeloma patient collective has a high prevalence of pre-existing cardiovascular comorbidities. In addition, the primary disease process contributes to cardiovascular complications. With the beginning of anti-tumor therapy, an increased incidence of cardiovascular complications in myeloma patients can be determined. This includes hypertension, left ventricular dysfunction, heart failure and both arterial and venous thromboembolic events.

Proteasome inhibitors including bortezomib and carfilzomib, and immunomodulatory agents, e.g. lenalidomide, represent cornerstone therapies for multiple myeloma. The most common therapy choices are Bortezomib-based therapy (VCD, VC) and Carfilzomib-based therapy (KRD, KD). Induction therapy is given 4-6 cycles followed by autologous hematopoietic cell transplantation. Thereafter, many patients receive consolidation therapy. In patients not eligible for autologous hematopoietic cell transplantation, a prolonged course of initial chemotherapy is typically administered. The proteasome inhibitor Bortezomib is used predominately in the front line setting, while second-generation carfilzomib is used in relapsed/refractory disease.

Despite their efficacy, increased rates of cardiovascular complications occur in patients exposed to these particular therapies. Higher incidences of cardiac adverse events including hypertension, arrhythmia, heart failure, ischemic heart disease and cardiomyopathy has been reported in patients receiving carfilzomib and bortezomib. Immunomodulatory agents are known to increase the risk of venous thromboembolic disease particularly when combined with dexamethasone or other chemotherapy. Furthermore, increased incidence of myocardial infarction (MI) and cerebrovascular events has been demonstrated in patients treated with lenalidomide. The mechanism of PI- and IMiD-associated cardiotoxicity is not fully elucidated. PIs inhibit proteasome activity, leading to the accumulation of abnormal proteins which in turn activates apoptotic pathways in myeloma cells. IMiDs bind cereblon, a component of the E3 ubiquitin ligase which promotes proteasome-mediated degradation of the transcription factors, IKZF1 and IKZF. It is unclear if the protein degradation properties of these drugs contribute to cardiotoxicity, although clinical features of the toxicity suggest endothelial cell injury and dysfunction. It is possible that CV events may be augmented when these two classes of medications are co-administered and further enhanced by the additional endothelial stress conferred by steroids. The detailed mechanism by which proteasome inhibitors and immunomodulatory agents lead to increased cardiovascular events is not established at this time.

Endothelial dysfunction, as a possible mechanism of cardiovascular toxicity, is difficult to assess. Flow-mediated dilation (FMD) is an noninvasive method to measure endothelial function by assessing the change in the vasodilatative reserve of the brachial artery. Several independent recent investigations implicate that vascular (endothelial) dysfunction precedes hypertension and heart failure. This has been related to a reduced level of metabolites of the l-arginine-nitric oxide (NO) signaling pathway.

Hypothesis:

1. Anti-myeloma therapy exert vascular toxicity by limiting endothelial function. Endothelial function, assessed by the change in the vasodilatative reserve of the brachial artery (flow-mediated dilation = FMD) decreases after myeloma therapy.
2. Patients with multiple myeloma have a limited endothelial function compared to a healthy control group.

Study design:

A total of 40 myeloma patients will be examined. Measurements will be taken at baseline, 1 month 6 month after myeloma therapy. Patients should not have received chemotherapy for at least 3 months. Furthermore a healthy sex- and age-matched control group will be examined.

Primary endpoint:

• Endothelial function, assessed by the change in the vasodilatative reserve of the brachial artery (flow-mediated dilation = FMD), between baseline and 1 month data

Secondary endpoints:

* Endothelial function, assessed by the vasodilatative reserve of the brachial artery (flow-mediated dilation = FMD) between baseline data in myeloma patients and control group
* Change of left ventricular pump function (3D-EF, global longitudinal strain)
* Alteration of echocardiographic parameters of diastolic dysfunction
* Change in dyspnea symptoms (NYHA Classification)
* Modification of cardiac biomarkers (NT-pro BNP, Troponin)
* Change of circulating NO-Pool
* Change in metabolomics (Biobank)
* Change in arterial stiffness and augmentation index
* Change of quality of life rated according to Medical Outcomes Short-Form Survey, SF-36, Minnesota Living With Heart Failure Questionnaire
* Change in blood pressure

Vascular Functions in Myeloma Patients During Anti-tumor Therapy

Characterization of Vascular Functions in Myeloma Patients Before and During Anti-tumor Therapy

Assesed by E, E/A, E/e', IVRT, DT, e', e'/a', TEI index, sPAP, according to ASE/EACVI GUIDELINES AND STANDARDS, Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography: An Update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging, Sherif et al, 2016, J Am Soc Echocardiogr, 2016

Levels of arginine, citrulline, ornithine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and N-monomethylarginine (MMA)

Augmentation index (AIx), the pressure difference between the shoulder on the pressure wave and systolic pressure expressed as a ratio of pulse pressure is widely used as a proxy of wave reflection

The questionnaire is comprised of 21 important physical, emotional and socioeconomic ways heart failure can adversely affect a patient's life. After receiving brief standardized instructions, the patient marks a 0 (zero) to 5 scale to indicate how much each itemized adverse of heart failure has prevented the patient from living as he or she wanted to live during the past 4 weeks. The questionnaire is simply scored by summation of all 21 responses.

The SF-36 consists of 36 questions and is a general health questionnaire that provides information about the health status of the patient through 8 different dimensions. He makes statements about:

General Health Perception, Physical Health, Restricted physical role function, Physical pain, Vitality, Mental Healt, Restricted emotional role function, Social functioning. For the evaluation of the SF-36 questionnaire v1.0 you first recode all answers in predefined points using a recoding table. Then you calculate the average score of all questions of the respective health dimension, e.g. physical health, so you have 8 average points for the 8 dimensions. These 8 scores now describe the health status of the patient in their respective dimensions, which can then be assessed using comparison charts.

The possible score ranges from 0 to 100 points. 0 points represent the greatest possible restriction of health, while 100 points represent the absence of health restrictions.

University Hospital, Essen

Principal Investigator

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Coronary Artery Disease

Adenocarcinoma

Heart Diseases

Atherosclerosis

Ischemia

Myocardial Ischemia

Prostatic Neoplasms

Coronary Disease

Carcinoma

Neoplasms, Glandular and Epithelial

Arteriosclerosis

Arterial Occlusive Diseases

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

ISCHEMIC HEART DISEASE diagnostic

The purpose of the study: to increase the efficiency of diagnosis, treatment and prediction of the course of coronary heart disease in patients with adenocarcinoma of the prostate gland, depending on the hormonal status by determining the cardiovascular risk factors, factors of angiogenesis, structural and functional state of the heart, coronary vessels, kidney damage and their pharmacological correction.

Research methods:

1. general-clinical examination
2. Laboratory methods:

   * estimation of the generally accepted laboratory parameters
   * determination of blood lipid profile
   * Determination of the level of highly sensitive CRP by the method of immuno-enzyme analysis,
   * determination of the level of proteinuria, creatinine by the method of immuno-enzyme analysis with the subsequent calculation of GFR
   * determination of the level of insulin by the method of immuno-enzyme analysis with the subsequent calculation of indices of insulin resistance,
   * determination of the level of blood testosterone by the method of immuno-enzyme analysis,
   * determination of the levels of vascular-endothelial growth factor, angiosetamine by the immuno-enzyme assay,
3. Echo-doppler examination of vessels (endothelium-dependent vasodilatation with reactive hyperemia, determination of the thickness of CIM, GPI)
4. Ultrasound examination of the main vessels of the head and neck
5. ECG
6. Daily monitoring of BP
7. CT-angiographic examination of coronary vessels with the definition of the index of calcification
8. Statistical methods

Ischemic Heart Disease in Male With Prostate Adenocarcinoma

Ischemic Heart Disease in Male With Prostate Adenocarcinoma: Clinical and Pathogenetic Aspects of Diagnostics, Prognosis and Treatment

cardiovascular events development - myocardial infarction, stroke

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Supervised Physical Activity in Young Women With Early Breast Cancer During Neoadjuvant Chemotherpy	NCT06190600	Breast Cancer	High Intensity ... neoadjuvant tre... Standard Suppor...	18 Years - 40 Years	The Greater Poland Cancer Centre
Vascular Functions in Myeloma Patients During Anti-tumor Therapy	NCT03776331	Cardiooncology Myeloma Endothelial Dys...	Flow mediated d...	18 Years -	University Hospital, Essen
Ischemic Heart Disease in Male With Prostate Adenocarcinoma	NCT03474835	Ischemic Heart ... Prostate Adenoc...	ISCHEMIC HEART ...	-	Dnipropetrovsk State Medical Academy
Ischemic Heart Disease in Male With Prostate Adenocarcinoma	NCT03474835	Ischemic Heart ... Prostate Adenoc...	ISCHEMIC HEART ...	-	Dnipropetrovsk State Medical Academy

Spots Global Cancer Trial Database for cardiooncology