Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Symptoms and General Pathology

Prostatic Neoplasms

Hypoxia

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Signs and Symptoms, Respiratory

Patients randomized to this group will perform a wattmax test immediately followed by 4 intervals of high and low intensity based on percentage of wattmax. Immediately after the exercise bout is finished patients will receive one dose of pimonidazole hydrochloride (500 mg per m2 body surface) in order to quantify tumor hypoxia by pathological analyses after removal of the prostate by radical prostatectomy the following day.

Patients randomized to the control group will not be doing any exercise, but will after approximately 35 min from baseline blood sampling receive one dose of pimonidazole hydrochloride (500 mg per m2 bodysurface) in order to quantify tumor hypoxia by pathological analyses after removal of the prostate by radical prostatectomy the following day.

Patients randomized to the HIIT bout will perform one single supervised High Intensity Interval Training bout consisting firstly of a wattmax test on a stationary bike, in order to set the training intensity. This is followed by 10 minutes at low intensity at approximately 30% of wattmax. Subsequently patients will perform 16 min with 4 cycles with High and Low intensity. HI intervals consisting of 1 min with 100% of wattmax followed by 3 min recovery with the intensity load of 30% of wattmax.

High Intensity Interval Training bout

Sissal S Djurhuus, MD

Background and purpose: The purpose of this study is to investigate the effect of one acute exercise bout on tumor hypoxia in patients with localized prostate cancer undergoing radical prostatectomy.

The primary hypothesis is that exercise reduces tumor hypoxia and that the reduction is greater in patients performing one acute high intensity exercise bout compared to no training controls.

The investigators have not been able to identify any prior or current randomized trials investigating exercise and tumor hypoxia, and believe that such research is warranted and would be of great importance. Moreover there is a need for studies including biological measurements to allow a full assessment of the effect of exercise on diverse biomarkers and mechanistic pathways, which may influence cancer survival.

Subjects: Patients with histologically verified prostate adenocarcinoma scheduled for radical prostatectomy at Urologic Department, Rigshospitalet, Copenhagen, Denmark.

Methods: In this randomized controlled pilot study 30 patients with localized prostate cancer undergoing radical prostatectomy will be included and randomized 2:1 to either one single acute High Intensity Interval Training bout or usual care and no training the day prior to radical prostatectomy.

All patients will undergo assessment at inclusion (baseline) and the day prior to surgery.

Assessment includes: anthropometrics; blood pressure; resting hearth rate; hip and waist circumference, ECG, quality of life by self-report questionnaires; fasting blood sample measuring PSA (prostate specific antigen), cholesterol, triglycerides, insulin, c-peptide, HbA1c, glucose and inflammatory markers.

All patients will receive one dose of pimonidazole hydrochloride (500 mg per m2 body surface) in order to quantify tumor hypoxia by pathological analyses after removal of the prostate.

Biological tissue from tumor (primary prostate biopsies) will also be retrieved from the respective local pathological departments and from the perioperative prostate specimen and sent to protocol analyses.

The purpose of this study is to investigate the effect of one acute exercise bout on tumor hypoxia in patients with localized prostate cancer randomized to one single acute I) High Intensity Interval Training bout compared to (II) usual care and no training prior to radical prostatectomy.

In addition to this the aim is to investigate the effect of one exercise bout on tumor vessel morphology and to investigate the effect of one acute exercise bout on intratumoral immune cell infiltration and to investigate the modulation of tumor-metabolism, -biology and signaling in patients randomized to either one acute High Intensity Interval Training bout compared to usual care and no training, the day prior to surgery.

Moreover this study will explore the acute response in immune cells, hormones and cytokines in blood samples taken before, during and after a single exercise session, and will collect physiological (metabolic profile and metabolic inflammatory markers) and psycho-social (e.g. fatigue, emotional well-being, anxiety) information regarding patients randomized to either one acute High Intensity Interval Training bout compared to usual care and no training, the day prior to surgery.

The Effect of Exercise on Tumor Hypoxia in Men With Localized Prostate Cancer Undergoing Radical Prostatectomy.

The Effect of Exercise on Tumor Hypoxia in Men With Localized Prostate Cancer Undergoing Radical Prostatectomy - a Randomized Controlled Pilot Study

Quantification of tumor hypoxia will be assessed using pimonidazole staining

Intratumoral immune cell infiltration will be quantified using histological analyses

Tumor vessel morphology will be evaluated using histological analyses

Tumor samples will undergo proteomic analyses in order to uncover potential upregulated biomarkers

Changes in immune cells during an acute exercise bout will be measured in blood samples using flowcytometry

Concentration of epinephrine will be measured in blood samples by radioimmunoassay analyses.

Concentration of nor-epinephrine will be measured in blood samples by radioimmunoassay analyses.

Concentration of various interleukines will be measured in blood samples by measured in blood samples by Enzyme-Linked Immunosorbent Assay (ELISA) analyses.

Concentrations of TNFa will be measured in blood samples by Enzyme-Linked Immunosorbent Assay (ELISA) analyses.

Concentrations of IFNγ will be measured in blood samples by Enzyme-Linked Immunosorbent Assay (ELISA) analyses.

Concentration of CRP will be measured in fasting blood sample by standard laboratory methods.

Concentrations of total cholesterol will be measured in fasting blood samples by standard laboratory methods.

Concentrations of LDL- cholesterol will be measured in fasting blood samples by standard laboratory methods.

Concentrations of HDL- cholesterol will be measured in fasting blood samples by standard laboratory methods.

Concentrations of triglycerides will be measured in fasting blood samples by standard laboratory methods.

Concentrations of HbA1C will be measured in fasting blood samples by standard laboratory methods.

Concentrations of insulin will be measured in fasting blood samples by standard laboratory methods.

Concentrations of glucose will be measured in fasting blood samples by standard laboratory methods.

The participants in the HIIT group will undergo a maximal graded exercise test on a bicycle ergometer for evaluation of cardiovascular function and determination of the maximum watt (wattmax). The test starts with a 3 min warm up at 70 watt (the watts may have to be adjusted to the individual fitness level). Warm up is immediately followed by a 20 watt increase every 1 min until exhaustion. The maximum watt will be calculated.

Rigshospitalet, Denmark

Principal investigator

Respiratory Tract (Lung and Bronchial) Diseases

Skin and Connective Tissue Diseases

Digestive System Diseases

Heart and Blood Diseases

Immune System Diseases

Lung Neoplasms

Carcinoma

Breast Neoplasms

Inflammation

Carcinoma, Hepatocellular

Thromboembolism

Thrombosis

Embolism

Embolism and Thrombosis

Vascular Diseases

All Drugs and Chemicals

Anticoagulants

Antineoplastic Agents

Coagulants

Anti-Infective Agents

Amino Acids

Immunomodulating Agents

Rivaroxaban

Palbociclib

Factor Xa Inhibitors

Antithrombins

Antithrombin III

Protease Inhibitors

Serine Proteinase Inhibitors

HIV Protease Inhibitors

Enzyme Inhibitors

Protein Kinase Inhibitors

Serine

Cancer patients without any incidence of thromboembolism will be included if they are non-carriers of the targeted gene-related polymorphism (GRP).

Cancer patients without any incidence of thromboembolism will be included if they are carriers of the targeted gene-related polymorphism.

Cancer patients with incidence of thromboembolism will be included if they are carriers of the targeted gene-related polymorphism.

Cancer patients with incidence of thromboembolism will be included if they are carriers of the targeted gene-related polymorphism and will be subjected to Palbociclib treatment.

Cancer patients with incidence of thromboembolism will be included if they are carriers of the targeted gene-related polymorphism and will be subjected to anti-coagulant treatment.

Palbociclib will be administered at a dose of 125 mg oral on a 21/7 cycle.

Rivaroxaban will be administered at a dosage of 15 mg intravenously twice a day for 21 days, followed by 20 mg once daily for the subsequent 21 days.

diagnostics of patients' carriers or not of the risk allele(s)

Nehman Makdissy, Professor

Malak Naboulsi, MD

David Wehbe, MD

Samar Hamoui, PhD

Fida Ayoubi, PhD

Noha Ibrahim, PhD

Nadine Ghotme, PhD

Christelle Rahme, MD, MSc

Elisa Makdessi, MSc

Bassam Bou Deleh, MSc

Joelle Moustafa, MSc

Maria Mouawad, MSc

This study aims to assess biomarkers and their related polymorphisms in the context of cancer-associated thromboembolism, with a particular focus on their interaction with the immune system. The roles of immune checkpoints, inflammatory and angiogenesis factors, as well as circulating immune cells will be elucidated. Additionally, our investigation extends to the exploration of long non-coding RNAs (LncRNAs) and genes associated with the coagulation vascular system. Initially, these aspects will be evaluated in the context of colorectal cancer, with the intention to expand our research to other solid tumors.

The identification of these biomarkers and genetic factors holds the potential to revolutionize therapeutic approaches for patients with cancer-associated thromboembolism, shedding light on their chemotherapy resistance. The effectiveness of combining immunotherapy with targeted inhibitors like Palbociclib and anticoagulants such as Rivaroxaban, among other potential interventions, will be assessed.

This study aims to make significant contributions to the understanding of these critical aspects, ultimately leading to the development of more effective treatment strategies for cancer patients.

Cancer, especially solid tumors, remains a significant global health challenge despite ongoing advancements in risk factor identification and targeted therapies. Among the various complexities of cancer treatment, the relationship between cancer and thromboembolism, characterized by arterial and venous thrombosis, has attracted attention due to its significant impact on patient outcomes.

Cancer cells activate the coagulation system, leading to prothrombotic disorders in the vascular wall and promoting tumor progression. Patients with cancer, particularly those undergoing systemic chemotherapy, face an increased risk of thromboembolism due to abnormal blood clotting mechanisms.

Recent research has emphasized the importance of identifying novel biomarkers for risk assessment, prognosis determination, and treatment selection in cancer. Among these biomarkers, long non-coding RNAs (LncRNAs) and those of the vascular coagulation system have emerged as pivotal players in cancer development and progression. However, their role as prognostic and predictive biomarkers for cancer risk and treatment response remains relatively unexplored.

Understanding the complex interplay between cancer, immune responses, and thromboembolism is crucial. Immunological subsets, including central immune effector T cells (CD8+, CD25+), NK cells, and macrophages, have been linked to cancer prognosis. Furthermore, therapies that modulate the immune system, such as immunotherapy and cell-based therapies, hold promise for improving cancer treatment outcomes.

Most notably, these therapies exhibit immunomodulatory effects, triggering immunogenic cell death and preventing immunosuppression. However, their efficacy may be compromised in cases of cancer associated with clotting abnormalities within the circulatory system. Progenitor cells, including stem cells and endothelial progenitor cells (EPCs), are emerging as potential players in cancer therapy, offering new avenues for research.

Among the innovative approaches is the assessment of circulating immune and endothelial progenitor cells (termed "CIEs"), which may play significant roles in the mechanisms underlying cancer-associated thromboembolism. Understanding the relationship between these cells, inflammatory and angiogenic factors, immune checkpoint, and cancer progression could pave the way for improved cancer risk assessment and treatment strategies.

This study seeks to contribute to our understanding of the intricate connections between LncRNA, coagulation-related biomarkers, thromboembolism, immune responses, and cancer, using solid tumors as a representative example. By shedding light on these complex interactions, this study aims to identify potential biomarkers that can guide risk assessment and treatment decisions, ultimately improving the management of cancer patients.

Exploring Cancer-Associated Thromboembolism Prognosis Biomarkers and Polymorphisms

Unveiling Prognosis Cancer-Associated Thromboembolism Biomarkers and Their Related Polymorphisms: Exploring Their Involvement With Immune Circulating Cells and Therapeutic Reversibility

The outcome measure of VTE including DVT, PE, and other thromboembolic events will be assessed by : (1) Clinical Assessment: Clinical symptoms such as swelling and pain in the lower limbs, tenderness behind the lower leg and/or medial thigh, and supplementary evaluation with color ultrasound of the veins in both lower limbs (lower extremity venography); (2) Imaging: CT pulmonary arteriography (CTPA) will be employed in conjunction with related clinical manifestations such as dyspnea and shortness of breath for diagnosing PE; (3) Laboratory Criteria: Diagnostic criteria will also consider laboratory parameters, including elevated D-dimer levels (\> 1000 ng/mL), increased fibrinogen levels (\> 700 mg/dL), and shortened activated partial thromboplastin time (aPTT) (\< 20 sec).

The assessment of cancer progression will be conducted using the standardized TNM staging system and applying the Response Evaluation Criteria (RECIST) guideline (ver. 1.1). Clinical parameters, laboratory tests indicative of cancer progression (including tumor markers and histopathological analysis), and relevant imaging modalities (e.g., CT, MRI, or PET scans) will be employed to evaluate the extent of primary tumor growth, lymph node involvement, and the presence of distant metastases. Progression-Free Survival (PFS), a key primary clinical endpoint for assessing cancer progression, will be calculated as the duration (in months) from the date of enrollment in the study until the tumor progresses, new lesions appear, or until the participant's death from any cause. Cancer progression will be determined based on RECIST guidelines, considering an increase in tumor size or the appearance of new lesions according to imaging assessments and clinical evaluations.

The objective of this outcome is to identify and characterize novel biomarkers associated with thromboembolism and cancer progression. Specifically, the assessment will focus on Long Non-Coding RNAs (LncRNAs) such as CDKN2B and CDKN2B-AS1, and markers related to the vascular coagulation system including ACE, PAI-1, FXIII, and Prothrombin. This identification process will involve collecting biological samples (e.g., blood, tissue) from enrolled patients at the time of study enrollment. The assessment will analyze and evaluate the expression and polymorphisms of the studied genes (CDKN2B, CDKN2B-AS1, ACE, PAI-1, FXIII, and Prothrombin) using quantitative PCR (qPCR), with Ct (Cycle threshold) as the common unit of measure for all genes. This comprehensive assessment aims to enhance our understanding of the molecular signatures linked to thromboembolism and cancer progression, illuminating potential diagnostic and therapeutic avenues for improved patient outcomes.

This primary outcome assesses treatment response in patients undergoing Palbociclib therapy for controlling cancer progression and thromboembolism. The evaluation will employ RECIST criteria to measure the percentage change in tumor size, indicative of treatment effectiveness.

Analysis of overall survival and progression-free survival rates among groups

The objective of this secondary outcome is to examine genetic variants, with a specific focus on the rs1333049 G\>C polymorphism within the CDKN2B-AS1 gene. The screening for polymorphism(s) will be determined by genotyping analysis using TaqMan PCR-based genotyping for SNP identification.

Monitoring and reporting of adverse events related to the Palbociclib and Rivaroxaban treatment regimen.

This outcome aims to comprehensively assess immune cell populations involved in the immune response, including T cells, B cells, natural killer (NK) cells, dendritic cells (DCs), and macrophages. The objective is to characterize changes in immune cell subsets over time, providing insights into the immune response dynamics. The assessment will involve immunophenotyping using flow cytometry to quantify and analyze the different immune cell populations. The unit of measure for this assessment will be the percentage of change of T cells, B cells, NK cells, DCs, and macrophages in the total population. The percentage of change will be determined up to a period of 60 months relatively to their levels at the diagnostic time.

This outcome focuses on assessing the levels of cytokines secreted by immune cells, including interferons (IFNs), interleukins (ILs), and tumor necrosis factor (TNF). The objective is to understand cytokine dynamics and their role in the immune response. The assessment will involve cytokine profiling by flow cytometry or ELISA. The levels of IFNs, ILs, and TNF will be measured as a percentage of change over a period of 60 months, relative to their levels at the diagnostic time. This standardized approach of using a common unit of measure will enable a comprehensive and unified evaluation of cytokine variations, providing critical insights into the immune response dynamics throughout the study duration.

This outcome aims to evaluate the presence and distribution of TILs within the tumor microenvironment. The objective is to understand the role of TILs in the immune response against the tumor. The assessment will involve analyzing tissue samples for TIL presence and distribution by immunohistochemistry (IHC) or flow cytometry.

This outcome focuses on investigating the expression of immune checkpoint molecules, specifically programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). The objective is to understand the role of immune checkpoints in regulating the immune response. The assessment will involve evaluating immune checkpoint expression using techniques such as flow cytometry or PCR. The levels of PD-1 and CTLA-4 expression will be measured in the percentage of change over a period of 60 months, relative to their levels at the diagnostic time. Utilizing a standardized common unit of measure ensures a uniform assessment, allowing for a comprehensive understanding of the immune checkpoint dynamics and their impact on the immune response throughout the study's duration.

This outcome aims to assess alterations in angiogenic factors, with a specific focus on Vascular Endothelial Growth Factor (VEGF), in relation to treatment and study outcomes. VEGF is a key regulator of angiogenesis and is associated with tumor vascularization. The serum concentrations of VEGF-A/C will be measured by ELISA, providing valuable insights into the angiogenic processes linked to the immune response and their potential impact on treatment outcomes.

Haykel Hospital

Lebanese University

Principal Investigator, Professor

Central Nervous System Depressants

Ethanol

The HIIT-group will receive usual care plus a supervised aerobic High Intensity Interval Training program consisting of 4 weekly sessions of approximately 35 minutes.

Patients randomized to usual care control will receive the standard patient care program as provided by the Department of Urology, Rigshospitalet.

Supervised aerobic High Intensity Interval Training program consisting of 4 weekly sessions of approximately 35 minutes. Patients will perform a test of maximum cardio-respiratory (VO2 peak test). Using the patient's individual wattmax, a personalized exercise program will be prescribed.

After a light warm-up, patients will perform 25 min of aerobic high intensity interval training on a stationary bicycle, intervals will consist of cycles of HI intervals with 120% of wattmax for 1 min followed by recovery for 3 min at 30% of wattmax. Each session will be supervised by trained instructors to ensure proper technique, and progression in training load.

High Intensity Interval Training

The reference group will receive the standard patient care program as provided by the Department of Urology, Rigshospitalet.This includes information regarding smoking cessation and alcohol reduction and a physiotherapist consultation regarding pelvic floor exercises. This group is allowed to exercise on their own initiative or participate in any standard care hospital- or municipality-based exercise program. This will be monitored by self-report.

Usual Care Observational Control

Background and purpose: The purpose of this study is to investigate the effect of exercise on intratumoral natural killer (NK)-cell variability in patients with localized prostate cancer undergoing radical prostatectomy.

The primary hypothesis is that exercise induces epinephrine-mediated intratumoral natural killer (NK)-cell infiltration in patients with localized prostate cancer, and that the infiltration is greater in patients performing High Intensity Interval Training compared to usual care controls.

Currently there is a lack of randomized controlled trials examining different types of exercise in patients with localized prostate cancer. Moreover there is a need for studies including biological measurements to allow a full assessment of the effect of exercise on diverse biomarkers and mechanistic pathways, which may influence cancer survival.

Subjects: Patients with histologically verified prostate adenocarcinoma scheduled for radical prostatectomy at Urologic Department, Rigshospitalet, Copenhagen, Denmark.

Methods: In this randomized controlled pilot study 30 patients with localized prostate cancer undergoing radical prostatectomy will be included and randomized 2:1 to either High Intensity Interval Training (HIIT) exercise intervention or observational control receiving usual care from inclusion and until planned surgery (radical prostatectomy).

All patients will undergo assessments at inclusion (baseline) and at follow-up after the exercise intervention period (maximum 8 weeks) 3-5 days prior to surgery.

Assessments include: anthropometrics; blood pressure; resting hearth rate; cardiorespiratory fitness by cardiopulmonary exercise test (VO2 peak.); body composition by DXA scan; quality of life by self-report questionnaires; fasting blood sample measuring cholesterol, triglycerides, insulin, c-peptide, HbA1c, glucose, hormones and inflammatory markers.

Biological tissue from tumor (primary prostate biopsies) will be retrieved from the respective local pathological departments and from the perioperative prostate specimen and sent to protocol analyses.

The purpose of this study is to investigate the effect of exercise on the variability of intratumoral Natural Killer (NK)-cell infiltration in tumor biopsies taken before and after an exercise intervention in patients randomized 2:1 to one of two study arms: I) High Intensity Interval Training (HIIT) (N=20) or II) usual care, prior to radical prostatectomy.

In addition to this the investigators wish to investigate the effect of HIIT exercise on the infiltration of other immune cells into the tumor, tumor vessel morphology, modulation of tumor-metabolism, -biology and signaling.

Finally the aim is to explore the effect of pre-operative HIIT exercise on physiological (e.g. cardiovascular fitness, body composition, metabolic profile and metabolic inflammatory markers) and psycho-social (e.g. fatigue, emotional well-being, anxiety) endpoints relative to usual care.

PROstaTe Cancer - Exercise-STudy (PRO-TEST)

Effect of Different Exercise Regimens on Intratumoral Natural Killer (NK) Cell Variability in Men With Localized Prostate Cancer Undergoing Radical Prostatectomy - a Randomized Controlled Pilot Study

Natural killer (NK)-cell infiltration will be quantified using histological analyses.

Tumor vessel morphology will be evaluated using histological analyses.

Tumor samples will undergo proteomic analyzes in order to uncover potential upregulated biomarkers.

Quantification of immune cells will be measured in blood samples by flowcytometry analyses.

Concentrations of epinephrine will be measured in blood samples by radioimmunoassay analyses.

Concentrations of nor-epinephrine will be measured in blood samples by radioimmunoassay analyses.

Concentrations of IL-1 (Interleukin 1) will be measured in blood samples by Enzyme-Linked Immunosorbent Assay (ELISA) analyses.

Concentrations of IL-2 (Interleukin 2) will be measured in fasting blood samples by Enzyme-Linked Immunosorbent Assay (ELISA) analyses.

Concentrations of IL-6 (Interleukin 6) will be measured in fasting blood samples by Enzyme-Linked Immunosorbent Assay (ELISA) analyses.

Concentrations of IL-8 (Interleukin 8) will be measured in fasting blood samples by Enzyme-Linked Immunosorbent Assay (ELISA) analyses.

Concentrations of IL-10 (Interleukin 10) will be measured in fasting blood samples by Enzyme-Linked Immunosorbent Assay (ELISA) analyses.

Concentrations of IL- 15Rα (IL- 15 receptor alpha) complex will be measured in blood samples by Enzyme-Linked Immunosorbent Assay (ELISA) analyses.

Concentrations of LDL-cholesterol will be measured in fasting blood samples by standard laboratory methods

Concentrations of HDL-cholesterol will be measured in fasting blood samples by standard laboratory methods

Concentrations of triglycerides will be measured in fasting blood samples by standard laboratory methods

Concentrations of HbA1C will be measured in fasting blood samples by standard laboratory methods

Concentrations of Insulin will be measured in fasting blood samples by standard laboratory methods

Body weight and anthropometrics (height, waist and hip circumference) will be assessed using standard procedures. Resting heart rate and blood pressure (Microlife, BPA100) will be determined in a supine position. Body composition (fat mass, bone mass and fat-free mass) and bone mineral density are analyzed by whole-body dual-energy X-ray absorptiometry (DXA) scan (Lunar, Lunar Corporation Madison, Wisconsin, USA). Transverse scans at 1 cm intervals are made from head to toe measuring the absorption of x-ray beams at two different energy levels as these are sent through the body. Since the different chemical compounds in the body absorb the intensity of the X-rays differently, the scan allows for a valid determination of bone mass, fat mass and fat-free/bone-free mass

The participants will undergo a maximal graded exercise test on a bicycle ergometer for evaluation of cardiovascular function and determination of the peak oxygen uptake (VO2peak). The test starts with a 5 min warm up at 70 watt (the watts may have to be adjusted to the individual fitness level). Warm up is immediately followed by a 20 watt increase every 1 min until exhaustion. Ventilation and expired gases will be measured during the test via an indirect calorimetric system, and heart rate will be assessed simultaneously.

The participants will undergo a maximal graded exercise test on a bicycle ergometer for evaluation of cardiovascular function and determination of the maximum watt (wattmax). The test starts with a 5 min warm up at 70 watt (the watts may have to be adjusted to the individual fitness level). Warm up is immediately followed by a 20 watt increase every 1 min until exhaustion. The maximum watt will be calculated.

Patient reported quality of life is measured by Functional Assessment of Cancer Treatment (FACT)

Patient reported sleep quality is measured by the Pittsburgh Sleep Quality Index (PSQI) questionaire.

Patient reported Anxiety and Depression is measured by the Hospital Anxiety and Depression Scale (HADS).

Patient reported physical activity is measured by the International Physical Activity Questionaire (IPAQ) - short form.

T-cell infiltration will be quantified using histological analyses.

MD, PhD student

Pain

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Adjuvants, Anesthesia

Analgesics

Antipyretics

Bupivacaine

Fentanyl

Analgesics, Opioid

Acetaminophen

Anesthetics

Anesthetics, Local

Narcotics

Anesthetics, Intravenous

Anesthetics, General

Analgesics, Non-Narcotic

Epidural catheter: Bupivacain 1,0 mg/ml + Fentanyl 2 micrograms/ml. Oral analgesia: Paracetamol, NSAID and placebo tablets.

Epidural analgesia: Placebo. Oral analgesia: Paracetamol, NSAID and opioids tablets.

Bupivacain to be given in epidural catheter

Bupivacaine in epidural catheter

Fentanyl to be given in epidural catheter

Fentanyl in epidural catheter

Placebo (for Bupivacain and Fentanyl i epidural catheter)

Oral Paracetamol

Oral NSAID

Oral opioids

Placebo tablets to be given instead of oral opioids

Placebo (for oral opioids)

Jimmy H Holm, MD

Whereas it, in the case of conventional thoracotomy, has been demonstrated that thoracic epidural analgesia is more effective than systemic opioids in terms of pain relief and preservation of postoperative pulmonary function, the efficacy of epidural analgesia in video-assisted thoracic surgical (VATS) procedures, has not been sufficiently studied, but a beneficial effect might very well be present.

On the other hand, the risks associated with placement of a thoracic epidural catheter are well known and if similar pain relief can be achieved without it with no or only insignificant alternative side effects, this would be preferable.

The literature regarding the usefulness of epidural analgesia for reducing pain in Video-Assisted Thoracic Surgery is, at best, scarce with two small studies showing some effect and two showing no difference, none of the studies being blinded randomized controlled trials of adequate size.

The SEAVATS Study will try to answer this question.

Study plan:

The hypothesis is that there is no difference in the amount of pain the patients will experience after VATS for pulmonary neoplasms.

Study design and setting:

The project is designed as a prospectively, double blinded, randomized, placebo controlled study comparing pain in two groups of patients.

Both groups of patients will:

* Have a epidural catheter placed.
* Receive a basis level of analgesics consisting of paracetamol and a nonsteroidal anti- inflammatory drug combined with a nerveblock placed intercostally during surgery.
* Have access to i.v. opioids as needed for any experienced pain after surgery.

One group of patients will be given local anaesthetics through the epidural catheter supplemented with placebo medication orally while the other group will receive saline in the epidural catheter supplemented with opioids orally.

Data collection:

Data will, during hospitalization, be collected in the operating theatre, in the postoperative care unit and in the surgical ward. Six months after surgery a questionnaire will be send to the patients to do follow-up regarding residual sequelae after surgery and placement of epidural catheter. Further follow-up with questionnaire has been planned for subsequent years.

As a secondary objective, in fifty-six of the patients from The SEAVATS Study, blood samples will be gathered during surgery and one hour and 24 hours after surgery, and compared with pre-operative levels.

These blood samples will be analysed for immune cells (NK-cells, levels and activity) and cytokines (IL-6, IL-10, IL-12 and IFN-gamma) as indicators of immunological response to surgery.

Research ethics:

The project has obtained ethics approval from The Regional Scientific Ethical Committees for Southern Denmark and acceptance to perform clinical research has been granted by The Danish Health and Medicines Authority. Consent to data collection has been provided by The Danish Data Protection Agency. Before entering the project, consent will be obtained from all patients. Rigorous data security will be maintained for five years and afterwards all data will be deleted. The Study is registered with The European Union Drug Regulating Authorities Clinical Trials Database (EudraCT) with EudraCT number 2014-000760-18 and is monitored by The Good Clinical Practice unit for Southern Denmark.

Supplementary Epidural Analgesia in Video-Assisted Thoracic Surgery (VATS) - The SEAVATS Study

Levels of NK-cells will be examined as an indicator of immunological response to surgery.

(The secondary outcomes "Immune cells", "Cytokines" and "Survival after VATS" should rightly have been registered in a separate sub study with a separate ClinicalTrials entry with "Immune cells - NK cell levels" as primary outcome measure and "Immune cells - NK cell activity", Cytokines" and "Survival after VATS" as a secondary outcomes as a separate sample size calculation was done to determine the needed inclusion for this part of the study. Now, instead, these outcomes will be defined as "Other Pre-specified Outcomes" with this explanation.)

The NK-cell activity will be examined as an indicator of immunological response to surgery.

(The secondary outcomes "Immune cells", "Cytokines" and "Survival after VATS" should rightly have been registered in a separate sub study with a separate ClinicalTrials entry with "Immune cells - NK cell levels" as primary outcome measure and "Immune cells - NK cell activity", Cytokines" and "Survival after VATS" as a secondary outcomes as a separate sample size calculation was done to determine the needed inclusion for this part of the study. Now, instead, these outcomes will be defined as "Other Pre-specified Outcomes" with this explanation.)

Levels of cytokines (IL-6, IL-10, IL-12 and IFN-gamma) will be examined as indicators of immunological response to surgery.

(The secondary outcomes "Immune cells", "Cytokines" and "Survival after VATS" should rightly have been registered in a separate sub study with a separate ClinicalTrials entry with "Immune cells - NK cell levels" as primary outcome measure and "Immune cells - NK cell activity", Cytokines" and "Survival after VATS" as a secondary outcomes as a separate sample size calculation was done to determine the needed inclusion for this part of the study. Now, instead, these outcomes will be defined as "Other Pre-specified Outcomes" with this explanation.)

Postoperative survival analysis. (The secondary outcomes "Immune cells", "Cytokines" and "Survival after VATS" should rightly have been registered in a separate sub study with a separate ClinicalTrials entry with "Immune cells" as primary outcome measure and "Cytokines" and "Survival after VATS" as a secondary outcomes as a separate sample size calculation was done to determine the needed inclusion for this part. Now, instead, these outcomes will be defined as "Other Pre-specified Outcomes" with this explanation.) (text initially added October 27th 2021, as the text was by mistake no included in the update after the protocol amendment 27 July 2016)

Self reported pain intensity 5 times a day both in rest and during activity until chest tube is removed or day 4 after operation is reached.

The consumption of i.v. opioids is registered daily until chest tube is removed or day 4 after operation is reached.

The duration of the surgical procedure will be registered.

Procedural time and competence level of MD placing catheter

Side effects observed using epidural analgesia including itching, nausea, vomiting, procedural pain, hypotension, dizziness, respiratory depression, reduced pulmonary function.

Questionnaire sent to patients 6, 12, 24 and 60 months after surgery. (criteria edited as part of a protocol amendment July 27th 2016 for a subsequent biomarkers study).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
The Effect of Exercise on Tumor Hypoxia in Men With Localized Prostate Cancer Undergoing Radical Prostatectomy.	NCT03675529	Prostate Cancer	High Intensity ...	18 Years -	Rigshospitalet, Denmark
The Effect of Exercise on Tumor Hypoxia in Men With Localized Prostate Cancer Undergoing Radical Prostatectomy.	NCT03675529	Prostate Cancer	High Intensity ...	18 Years -	Rigshospitalet, Denmark
Exploring Cancer-Associated Thromboembolism Prognosis Biomarkers and Polymorphisms	NCT06065592	Cancer Solid Tumor Thromboembolism Cardiovascular ... Immune System D... Inflammatory Di... Colon Cancer Breast Cancer Prostate Cancer Hepatocellular ... Lung Cancer Chemotherapy Immunotherapy	Palbociclib Rivaroxaban SNP	18 Years -	Lebanese University
PROstaTe Cancer - Exercise-STudy (PRO-TEST)	NCT02954783	Prostate Cancer	High Intensity ... Usual Care Obse...	18 Years -	Rigshospitalet, Denmark
Supplementary Epidural Analgesia in Video-Assisted Thoracic Surgery (VATS) - The SEAVATS Study	NCT02359175	Lung Neoplasms Pain Immune Suppress...	Bupivacaine in ... Fentanyl in epi... Placebo (for Bu... Oral Paracetamo... Oral NSAID Oral opioids Placebo (for or...	18 Years -	Odense University Hospital
Immunophenotyping From Blood of Patients With Malignant Gliomas	NCT02022384	Anaplastic Astr... Glioblastoma Mu...	Blood sample an...	18 Years -	University of Erlangen-Nürnberg Medical School
Exploring Cancer-Associated Thromboembolism Prognosis Biomarkers and Polymorphisms	NCT06065592	Cancer Solid Tumor Thromboembolism Cardiovascular ... Immune System D... Inflammatory Di... Colon Cancer Breast Cancer Prostate Cancer Hepatocellular ... Lung Cancer Chemotherapy Immunotherapy	Palbociclib Rivaroxaban SNP	18 Years -	Lebanese University
Immune Cells as a New Biomarker of Response in Patients Treated by Immunotherapy for Advanced Hepatocellular Carcinoma	NCT05044676	Hepatocellular ...	patients with h...	18 Years - 90 Years	Assistance Publique - Hôpitaux de Paris
Supplementary Epidural Analgesia in Video-Assisted Thoracic Surgery (VATS) - The SEAVATS Study	NCT02359175	Lung Neoplasms Pain Immune Suppress...	Bupivacaine in ... Fentanyl in epi... Placebo (for Bu... Oral Paracetamo... Oral NSAID Oral opioids Placebo (for or...	18 Years -	Odense University Hospital
Immune Profile and Prognosis of Malignant Liver Tumors With Radiofrequency Ablation (RFA) Therapy	NCT04707547	Liver Cancer	immunotherapy w... Radiofrequency ...	20 Years -	Taipei Medical University WanFang Hospital

Spots Global Cancer Trial Database for immune cells

Every month we try and update this database with for immune cells cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.