Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Skin and Connective Tissue Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Lung Neoplasms

Melanoma

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Male Urogenital Diseases

Adoptive Cell Transfer of tumor infiltrating lymphocytes that were selected for tumor reactivity by the expression of cell surface proteins CD39 an CD103 and expanded in vitro. A suspension of 1-40 billion cells will be delivered one time by intravenous infusion.

Adoptive Cell Transfer of tumor infiltrating lymphocytes that were selected for tumor reactivity by the expression of cell surface proteins CD39 and CD103 and expanded in vitro in the presence of PH-762, a silencing RNA that reduces the expression of the checkpoint inhibitor PD-1. A suspension of 1-40 billion cells will be delivered one time by intravenous infusion.

intravenous infusion of T cell suspension

DP CD8 TIL

DP CD8 TIL KD

Low dose IL-2 delivered subcutaneously for 1, 2 or 3 weeks

Low dose IL-2

Colin J Thalhofer, PhD

Ryan D Montler, MBA

Christopher B Fountain, RN, BSN, OCN

Brendan D Curti, MD

The subject of this study is the adoptive transfer of selected autologous tumor infiltrating lymphocytes (TIL) after in vitro expansion for the treatment of solid tumor malignancies. The TIL selection process is based on evidence showing that CD8+ TIL which co-express both CD39 and CD103 harbor the bulk of tumor-reactivity and that the remaining CD8 TIL is mainly composed of non-tumor reactive bystander cells. All of the expanded TIL that are produced (1-40 billion are expected) will be delivered in the form of a cell suspension to the participants by intravenous infusion. It is proposed that these selected TIL will produce a more potent and efficacious treatment of late-stage cancer.

Our research identified a subpopulation of CD8 tumor infiltrating lymphocytes (TIL) highly enriched for tumor reactivity that can be identified and isolated based on the co-expression of CD39 and CD103. The investigators refer to this tumor-reactive cell population as DP CD8 TIL. The DP CD8 TIL can constitute as few as 2% and up to 70-80% of the CD8 TIL directly isolated from tumors, suggesting that in any given patient a substantial percentage of their CD8 TIL can be bystanders lacking tumor specificity. The CD8 DP TIL were highly enriched for cells that recognize autologous tumor as evidenced by interferon gamma production, 4-1BB upregulation and autologous tumor cell killing. The investigators also found that T cell receptors within the CD8 DP TIL population share very little overlap with the other sub-populations of CD8 TIL, suggesting that they have a distinct antigen recognition pattern.

The DP CD8 TIL express high levels of PD-1 especially when encountering tumor Ag(s) in situ. Pre-clinical experiments have shown that the potency of DP CD8 TIL can be enhanced by decreasing PD-1 checkpoint expression by incubating them with siRNA that targets PD-1. The investigators hypothesize that transient knockdown of PD-1 expression will enable DP CD8 TIL to initiate a more effective and persistent anti-tumor response without increasing toxicity. The investigators refer to DP CD8 TIL after PD-1 knockdown as DP CD8 TIL KD. Although preclinical experiments have shown the value of siRNA modulation of PD-1 in DP T cells, this strategy has not been studied in humans. The main goals of this phase I first-in-human study are to define toxicity and understand the biology and anti-tumor activity of DP CD8 TIL alone and with siRNA PD-1 modulation. Thus, the trial is designed as a randomized comparison of DP CD8 TIL and DP CD8 TIL KD with comprehensive immune monitoring as detailed below.

Lymphodepleting chemotherapy just before adoptive transfer facilitates proliferation and persistence of adoptively transferred T cells as has been demonstrated in other adoptive cellular therapy trials over the last 30 years. Similarly, interleukin-2 (IL-2) administered after adoptive transfer enhances T-cell proliferation, persistence, and cytotoxicity. The investigators have also performed pre-clinical experiments confirming the need for IL-2 after DP CD8 TIL adoptive transfer to achieve maximum antitumor effect in a human xenograft model. Cyclophosphamide and fludarabine will be given prior to adoptive transfer of the DP CD8 TIL and high dose IL-2 (600,000 IU/kg IV with a maximum of 6 doses over 6 days) will be administered starting within 24 hours of the adoptive transfer followed by subcutaneous IL-2 in dose-escalation cohorts of IL-2, 5 MIU/m2 TIW starting on day +8 for 1 weeks, 2 weeks or 3 weeks if tolerated.

Autologous adoptive T cell therapy provided to three cohorts of patients receiving supportive subcutaneous IL-2 therapy for one, two ,or three weeks. Each cohort will be randomized between therapy with DP CD8 TIL or DP CD8 TIL having PD-1 expression reduced by silencing RNA during invitro cell expansion

Adoptive Cell Therapy Using Cancer Specific CD8+ Tumor Infiltrating Lymphocytes in Adult Patients With Solid Tumors

Phase I Randomized Open Label Trial Investigating Adoptive Transfer of CD39+CD103+CD8+ Tumor-isolated T Cells (AGX148) Alone or Combined With siRNA Modulation of PD-1 (AGX148/PH-762) in Patients With Advanced Solid Tumors

Frequency and severity of treatment-related adverse events as assessed by CTCAE v5.0 in participants treated with DP CD8 TIL adoptive cell therapy with and without ex vivo siRNA PD-1 modulation after lymphodepleting chemotherapy and followed by high-dose and low-dose IL-2.

Objective response using Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria in participants treated with DP CD8 TIL adoptive cell therapy with and without ex vivo siRNA PD-1 modulation after lymphodepleting chemotherapy and followed by high-dose and low-dose IL-2.

Adoptively transferred T cells circulating in the peripheral blood will be identified and quantified over time to identify any differences in the persistence of DP CD8 TIL and DP CD8 TIL KD.

within each cohort of participants receiving 1, 2 or 3 weeks of low-dose subcutaneous IL-2 administration

between different cohorts of low-dose subcutaneous IL-2 administration

Phio Pharmaceuticals Inc.

Providence St Joseph Health

AgonOx, Inc.

Blood and Lymph Conditions

Skin Neoplasms

Lymphedema

Lymphatic Diseases

Patients with any type of skin melanoma (at the level of the lower limb), urogenital or gynaecological cancer scheduled for lymph node dissection

screening of patients at risk for developing unilateral or bilateral lower limb lymphedema

clinical assessment

Tessa De Vrieze, Dr.

Lymphedema is a chronic, debilitating disorder characterized by abnormal tissue swelling, adipose deposition and tissue fibrosis, resulting from disruption, blockage, or genetic abnormalities of the lymphatic system. Secondary lymphedema is an acquired lymphedema due to trauma, surgery, radiotherapy or infection among others resulting in a decreased transport capacity of the lymphatic system. This can be combined with an additional load on the lymphatic system due to obesity, venous hypertension or a wound, among others. Advances in oncologic treatment have led to an ever-increasing number of cancer survivors over time. As a result, morbidities related to this treatment (such as secondary lymphedema) are likely to increase too.

Risk factors for the development of LLL after treatment for (gynaecological) cancer are: pelvic and para-aortic lymphadenectomy, the number of pelvic lymph nodes removed, adjuvant radiotherapy, adjuvant chemotherapy, increasing BMI/ BMI ≥25 kg/m², lymphocyst formation, increasing age, increasing time since surgery and insufficient physical activity level.

To the investigators knowledge, no evidence exists regarding which (combination of) measuring methods are most sensitive to detect early lymphedema at the lower limbs after the treatment of cancer. Thresholds for identifying subclinical edema on one or both lower limbs are lacking.

Therefore the investigators want to develop a screening set for patients at risk for developing LLL. Which measurement method (and which criterion) shows the best diagnostic accuracy in screening patients at risk for LLL after cancer treatment? And: What is the added value of combining different measurement methods in terms of diagnostic accuracy?

Development of a Clinical Screening, Diagnostic and Evaluation Tool for Patients With Lower Limb Lymphedema: Aim 2

Development of a Clinical Screening, Diagnostic and Evaluation Tool for Patients With Lower Limb Lymphedema: Development of a Screening Set for Patients at Risk for Developing LLL

Sensitivity of reliable and clinical feasible measurement methods (resulted from aim 1: NCT05269264) regarding the screening of patients at risk for developing unilateral or bilateral LLL at 6 weeks, 6, and 12 months post-surgery

Specificity of reliable and clinical feasible measurement methods (resulted from aim 1: NCT05269264) regarding the screening of patients at risk for developing unilateral or bilateral LLL at 6 weeks, 6, and 12 months post-surgery

Diagnostic accuracy of reliable and clinical feasible measurement methods (resulted from aim 1: NCT05269264) regarding the screening of patients at risk for developing unilateral or bilateral LLL at 6 weeks, 6, and 12 months post-surgery

Dependent variable = presence of lower limb lymphoedema Independent variable= Age (years) will be self-reported through interview.

Dependent variable = presence of lower limb lymphoedema Independent variable= Baseline physical activity level : will be assessed with the International Physical Activity Questionnaire (IPAQ).

The IPAQ is a 27-item self-reported measure of physical activity for use with individual adult patients aged 15 to 69 years old. Results can be reported in categories (low activity levels, moderate activity levels or high activity levels) or as a continuous variable (MET minutes a week). MET minutes represent the amount of energy expended carrying out physical activity.

Dependent variable = presence of lower limb lymphoedema Independent variable= Educational level: will be self-reported through interview.

Dependent variable = presence of lower limb lymphoedema Independent variable= baseline Body Mass Index

Dependent variable = presence of lower limb lymphoedema Independent variable= baseline comorbidities

Comorbidities will be reported through a self-developed co-morbidity questionnaire, based on IDEWE questionnaire.

Dependent variable = presence of lower limb lymphoedema Independent variable= Type of cancer Information regarding the type of cancer is collected by exploring the patient's medical file.

Dependent variable = presence of lower limb lymphoedema Independent variable= Tumor stage

Information regarding the tumor stage of is collected by exploring the patient's medical file.

Dependent variable = presence of lower limb lymphoedema Independent variable= Lymph node stage

Information regarding the lymph node stage of is collected by exploring the patient's medical file.

Dependent variable = presence of lower limb lymphoedema Independent variable=Number of positive lymph nodes: is collected through the patient's medical file.

Information regarding the complications related to the surgery as well as adjuvant therapies is collected. Surgical complications will be assessed according to the Clavien-Dindo Classification of Surgical Complications.

Cancer treatment characteristics are collected (i.e. type of surgery, type of lymph node dissection, number of lymph nodes removed, presence of postoperative drain, number of positive lymph nodes, adjuvant therapies; by exploring the patient's medical file.

Type of lymph node dissection: Limited- Standard- Extended- Super extended

Cancer treatment characteristics are collected (i.e. type of surgery, type of lymph node dissection, number of lymph nodes removed, presence of postoperative drain, number of positive lymph nodes, adjuvant therapies; by exploring the patient's medical file.

Cancer treatment characteristics , including adjuvant radiotherapy are collected; by exploring the patient's medical file.

Calculation of the proportion of patients with leg (or foot) lymphedema, defined as 5.0% or more increase of the leg (or foot) volume in each leg (or foot), at a certain time point, compared to the volumes at baseline; OR patients with a score of at least 5 out of 52 on the detect-OL questionnaire in case it is clearly indicated whether symptoms are present in one or both legs (in order to be able to categorize patients to the "unilateral LLL" or "bilateral LLL" group).

Additionally, the proportion of presence of LLL in patients having received a lymph node dissection due to gynaecological cancer vs. due to urogenital cancer vs. due to skin melanoma will be compared. The distribution of LLL (unilateral vs. bilateral, regions of the lower limb) will be encountered and compared.

Universitaire Ziekenhuizen KU Leuven

KU Leuven

Post-doctoral research fellow and physiotherapist, PhD in Biomedical Sciences (Catholic University of Leuven) and Medical Sciences (University of Antwerp)

Symptoms and General Pathology

Neoplasm Metastasis

Neoplastic Processes

All Drugs and Chemicals

Technetium Tc 99m Medronate

Radiopharmaceuticals

Injection of radioactive element (Tc-99m MDP) then imaging with gamma camera and low dose CT (SPECT/CT)

Tc-99m MDP and gamma camera

Maram M Shafeek, Resident

Samir S Mohamed, Professor

HebatAllah A Askar, Lecturer

Rehab M Helmy, Lecturer

The study aims to compare the diagnostic performance of planar bone scan and two bed SPECT/CT in detection of bone metastases in patients with urogenital cancer.

Genitourinary malignancies represent a heterogeneous group of diseases linked by anatomical and physiological function. Renal cell carcinoma (RCC); urothelial carcinoma of the bladder, ureter, and renal pelvis, and prostate adenocarcinoma (PC) are the most commonly encountered histological subtypes within this group. Planar bone scintigraphy (PBS) with di-phosphonate compounds is widely used, cost-effective and sensitive imaging modality for detecting osseous metastases especially in prostate cancer. However, it suffers from low specificity as well as low sensitivity in purely osteolytic lesions. Single-photon emission computed tomography (SPECT) is a three-dimensional acquisition method that has demonstrated greater sensitivity and specificity compared to planar images, especially for detecting vertebral metastases. The introduction of SPECT/CT images improves the lesion-to-background ratio, allows anatomic lesion localization, removes the superimposition of anatomical structures, such as urinary bladder activity, and provides anatomical data, thereby increasing the sensitivity, specificity and positive predictive value of bone scan. As the technology advances, current SPECT/CT machines have become capable of sequentially covering, and accurately merging, more than one field of view (FOV) in a reasonable time. In this study, we aim to compare the diagnostic performance of two-bed SPECT/CT images and planar bone scintigraphy in detection of bone metastases in genitourinary malignancies.

Two Bed SPECT/CT Versus Planar Bone Scintigraphy in Detection of Osseous Metastases in Patients With Genitourinary Malignancies

Analysis and comparison of diagnostic performance indices between two-bed SPECT/CT images and planar bone scans for the detection of osseous metastases in genitourinary malignancies.

Assiut University

Principal investigator

Nocturia

Polyuria

Lower Urinary Tract Symptoms

Urological Manifestations

Urination Disorders

Urologic Diseases

patients planned for transperitoneal pelvic lymph node dissection for treatment of urogenital cancer (including prostate or bladder cancer)

The information about lymphoedema and its prevention is given during the hospital stay by the physical therapist of the department of urology. Skincare consists of daily skin moisturizer of feet and legs and prevention and care of wounds. Active exercises are performed to gain endurance and muscle strength after surgery and to stimulate the blood and lymph circulation. The exercises are supervised by the home physical therapist. Frequency of the supervised exercises is gradually decreased. If a patient develops lymphoedema, he/she receives compression stockings.

usual care

Nele Devoogdt, Prof. Dr.

Charlotte Van Calster, MSc.

After the treatment of urogenital cancer, a person may develop lymphoedema of the leg(s) and/ or midline region. Clinical symptoms include abnormal tissue swelling, sensation of limb heaviness, erythema, pain, and impaired limb function. Lymphoedema can have a negative impact on quality of life (QoL) and the impact of lymphoedema on the cancer treatment decision making process is underestimated. A limited number of studies have evaluated the incidence rate of midline and leg lymphoedema after surgery for urogenital cancers and have investigated the prognostic variables. In addition, to the researchers knowledge, no evidence exists regarding which (combination of) clinical measuring methods are most sensitive to detect early lymphoedema at the lower limbs after the treatment of urogenital cancer. Therefore, in this prospective observational study, the epidemiology (i.e. incidence/ prevalence rate and prognostic variables) and the detection methods of lower limb lymphoedema after pelvic lymph node dissection for urogenital cancer will be investigated.

Additionally, the epidemiology of nocturia and nocturnal polyuria will be studied (since this information is also missing in literature).

Lymphoedema is caused by malfunction of the lymphatic system whether or not in combination with extra load on this system. Some patients develop lymphoedema after treatment for cancer: secondary lymphoedema or acquired lymphoedema. In 2018, 11 645 patients in Belgium were diagnosed with urogenital cancer cancer, including prostate and bladder cancer. A possible treatment consists of prostatectomy or cystectomy in combination with transperitoneal pelvic lymph node dissection. Patients who undergo treatment for cancer may develop lower limb lymphoedema or lymphoedema at midline. To the researchers knowledge, investigation of incidence of lower limb lymphoedema (LLL) is limited. Also, the prognostic variables for the development of LLL are unknown. Furthermore, no scientific evidence consists regarding which (combination of) clinical measurement methods are most sensitive to detect early LLL after transperitoneal pelvic lymph node dissection. Thresholds to identify subclinical lymphoedema in one or both legs are lacking. Besides lymphoedema in the lower limbs, treatment for cancer also often results in urinary problems. Especially urinary stress incontinence has been described in literature. However, in clinical practice, it is clear that prostatectomy is often associated with other urinary complications, as nocturia and nocturnal polyuria. To the researchers knowledge, there are no trials investigating the prognostic variables for the development of nocturia/ nocturnal polyuria after transperitoneal pelvic lymph node dissection for urogenital cancer.

Therefore, the researchers will execute a trial investigating the epidemiology (i. e incidence, prevalence and prognostic variables), detection methods and the feasibility of a trial about the early treatment of LLL after transperitoneal pelvic lymph node dissection for urogenital cancer. The epidemiology of LLL, nocturia and nocturnal polyuria will be investigated.

Participants: 150 patients undergoing a transperitoneal pelvic lymph node dissection for urogenital cancer will be included. These participants will be followed-up from baseline (pre-surgery) until 1 year post-surgery. All participants are evaluated at the University Hospitals Leuven, campus Gasthuisberg.

Procedure: The potential participant will be screened first to see if the patients meets the inclusion criteria. After signing the informed consent form, the participant will be followed in the prospective observational trial. The duration of the prospective observational trial is 2 years. Participants can be included until 1 year after the start of the trial.

Evaluation: There will be clinical evaluation of lymphoedema as well as treatment for lymphoedema. Participants in the prospective observational trial will be evaluated 4 times: baseline (pre-surgery), 6 weeks, 6 and 12 months post-surgery.

Treatment: All participants in the prospective observational trial receive standard of care. This consists out of information, skincare and exercises. The information about lymphoedema and its prevention is given by the physical therapist of the department of urology during the hospital stay. Skincare consists of daily moisturizer of legs and feet and prevention and care of wounds. The exercises are supervised by the home physical therapist. The frequency of the session at the physical therapist are gradually decreased.

Lymphoedema and Nocturia/Nocturnal Polyuria After Pelvic LND for Urogenital Cancer

Lymphoedema and Nocturia/ Nocturnal Polyuria After Pelvic Lymph Node Dissection (LND): Prospective Observational Study

Calculation of the proportion of patients who developed leg lymphoedema during a certain time interval (defined as 5.0% or more increase of the leg volume) and calculation of the proportion of patients who developed midline lymphoedema during a certain time interval (defined as 20% or more increase of the baseline water content at the prepubic region)

Dependent variable = presence of leg lymphoedema/ presence of midline lymphoedema Independent variable= Age (years) will be self-reported through interview.

Baseline fat mass will be measured using Bio-impedance Spectroscopy

Baseline physical activity level will be assessed with the International Physical Activity Questionnaire (IPAQ).

The IPAQ is a 27-item self-reported measure of physical activity for use with individual adult patients aged 15 to 69 years old. Results can be reported in categories (low activity levels, moderate activity levels or high activity levels) or as a continuous variable (MET minutes a week). MET minutes represent the amount of energy expended carrying out physical activity.

Educational level will be self-reported through interview.

Comorbidities will be reported through a self-developed co-morbidity questionnaire, based on IDEWE questionnaire.

Information regarding the type of urogenital cancer (prostate versus bladder) and the stage of the urogenital cancer is collected (i.e. histological subtype, PSA (if PCa), pTN stage, ISUP grade group (if PA); by exploring the patient's medical file.

Number of positive lymph nodes is collected through the patient's medical file.

Calculation of the proportion of patients with leg lymphoedema at a certain time point (defined as 5.0% or more increase of the leg volume) and calculation of the proportion of patients with midline lymphoedema at a certain time point (defined as 20% or more increase of the baseline water content at the prepubic region): 6 weeks, 6 and 12 months post-surgery

To investigate reliability, all participants with lower limb lymphoedema at 12 months post-surgery will be evaluated three times with each evaluation method: intra and interrater reliability will be determined

To determine feasibility of each method, time efficiency will be examined for each method: setup time (time needed to prepare the measurement), execution time ( time needed for a bilaterally execution of the measurement) and total time (required for the setup and the execution of the measurement) (min, sec)

limitations regarding clinical feasibility will be listed and scored (yes/no) for each method.

As "gold standard" to compare the different measurement methods with, every patient will be evaluated individually once by the project's international expert panel, during a monthly (virtual) meeting (2 up to 3h). They will decide whether patients should be labelled as showing 'presence of early signs of lower limb lymphoedema (1)' or 'no signs (0)'. Decision making will occur with an initial assessment of the experts, i.e. in advance of the monthly meeting. Then the project manager will lead the meeting on the basis of the assessments and subsequently conduct a new 'vote'. In case \>2/3 of the experts (= clear majority) decides a patient should receive a diagnosis of lymphoedema, then this patient receives the diagnosis.

outcomes resulting from the measurement method will be compared against the yes/no score regarding clinical presence of LLL from our international expert group

Calculation of the proportion of patients with nocturia/ nocturnal polyuria at a certain time point: baseline, at 6 weeks, 6 and 12 months post-surgery

Age (years) will be self-reported through interview

late-night fluid intake will be assessed through the micturition chart that (during 24 hours, in the week prior to the assessment visit) has to be filled in by the patient before surgery and at 6 weeks, 6 months and 12 months after surgery. The patient has to write down the time, frequency and quantity of urinating during the day and night. The time of drinking a consumption, the amount of a consumption and which consumption also has to be recorded.

late-night caffeine/alcohol use (3 hours before going to bed) will be assessed through the micturition chart that (during 24 hours, in the week prior to the assessment visit) has to be filled in by the patient before surgery and at 6 weeks, 6 months and 12 months after surgery. The patient has to write down the time, frequency and quantity of urinating during the day and night. The time of drinking a consumption, the amount of a consumption and which consumption also has to be recorded.

Baseline physical activity level will be assessed with the International Physical Activity Questionnaire (IPAQ).

The IPAQ is a 27-item self-reported measure of physical activity for use with individual adult patients aged 15 to 69 years old.

information regarding the type of urogenital cancer (prostate versus bladder) and the stage of the urogenital cancer is collected (i.e. histological subtype, PSA (if PCa), pTN stage, ISUP grade group (if PA); by exploring the patient's medical file.

information regarding the lymph node stage is collected by exploring the patient's medical file.

Surgical complications will be assessed according to the Clavien-Dindo Classification of Surgical Complications. Complications will be determined as 30-day, 90-day or late (\>90 days) complications.

Information about the type of lymph node dissection is collected by exploring the patient's medical file.

Type of lymph node dissection: Limited- Standard- Extended- Super extended

number of lymph nodes removed: by exploring the patient's medical file.

Cancer treatment characteristics , including radiotherapy are collected; by exploring the patient's medical file.

Cancer treatment characteristics are collected, including the presence of postoperative drain, are collected by exploring the patient's medical file.

The presence of leg lymphoedema (defined as 5.0% or more increase of the leg volume) and midline lymphoedema (defined as 20% or more increase of the baseline water content at the prepubic region)

Antineoplastic Agents

Atezolizumab

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Patients receive 2 x 3-weekly cycles of Atezolizumab (one infusion on the first day of each cycle) prior to cystectomy surgery.

ABACUS-2 Trial Coordinator

Thomas Powles

This study is being carried out to see if the drug atezolizumab can reduce the size of tumours in patients with types of urothelial cancer before surgery. Atezolizumab is designed to stop a protein called PD-L1 (programmed death-ligand 1) being expressed on the cancer, allowing the immune system to recognise the tumour cells as foreign bodies and attack them. Atezolizumab has been shown to have activity in urothelial cancer which has spread.

There two cohorts for this trial. One cohort will investigate the most common histological type of urothelial cancer (transitional cell carcinoma) outside the bladder, for example in the upper urinary tract. The other cohort will investigate rarer histological subtypes (such as such as squamous cell or adenocarcinoma) of urothelial cancer throughout the entire urinary system.

This study will be recruiting patients from hospitals in the UK, France and Spain. If a patient is eligible for the study and decides to take part, they will receive up to two 3-weekly cycles of atezolizumab. 4-8 weeks after being enrolled, the patient will have an operation to remove the bladder (cystectomy) or the kidney, ureter and part of the bladder (nephroureterectomy or distal ureteral resection) as per normal practice. Following surgery, they will attend three hospital visits (4,12 and 24 weeks after surgery) and their disease progress/survival will be followed over the next 2 years. The clinical team will compare the patient's tumour tissue samples,scan results and blood results from before and after treatment with atezolizumab in order to see how well the drug works and if it is safe. Many of the procedures involved in this study are offered as standard care and participation in this trial will not delay surgery.

Neoadjuvant Immune Checkpoint Inhibitor Treatment in Urothelial Cancer

Phase 2 Study of Neoadjuvant Immune Checkpoint Inhibitors in Urothelial Cancer

No microscopic evidence (pT0/Tis/Cis) of residual disease in the bladder based on histological evaluation of the resected bladder specimen collected during cystectomy (post-treatment) \[Bladder Cohort\]

- No microscopic evidence (pT0/Tis/Cis) of residual disease in the renal pelvis or ureter in the resected sample collected during radical surgery for upper tract disease (post-treatment) \[UTUC Cohort\]

ynamic changes in T cell subpopulations (CD8 and/or CD3) measured in tumour samples collected pre- and post-treatment.

Incidence, nature and severity of Adverse Events graded according to NCI-CTCAE v5.0. Surgical complications will be assessed by the Clavien-Dindo scoring system.

RR defined as a ≥30% decrease in tumour diameter from the baseline scan based on local investigator assessments.

DFS defined as time between the date of enrolment to first evidence of relapse based on local investigator assessments or death, whichever occurs first.

OS, defined as the time between the date of enrolment and death due to any cause.

Hoffmann-La Roche

Queen Mary University of London

Skin care, exercise and compression stocking:

The patient has to wear custom-made compression thigh stocking(s) in case of unilateral/ bilateral swelling of the leg and has to wear a bermuda in case of swelling of the midline region. The patient continues the skin care and continues/ restarts exercise therapy with the home physical therapist 2 times a week. Frequency of exercises is gradually decreased: M1-3 2x/w, M4-6 1x/w, M7-9 1x/M; M10-12 only self-exercises.

Usual care + manual lymph drainage. Manual lymph drainage is performed by the home physical therapist. Every session lasts for 30 minutes.

Frequency of manual lymph drainage is gradually decreased: M1-3 2x/w, M4-6 1x/w, M7-9 1x/M; M10-12 only self-MLD.

Manual lymph drainage

skin care, exercise and compression stocking

Usual care

After the treatment of urogenital cancer, a person may develop lymphoedema of the leg(s) and/ or midline region. Lymphoedema is the result of a dysfunction in the lymphatic system and is characterized by excessive retention of lymphatic fluid in the interstitial compartment, adipose deposition and chronic tissue inflammation resulting in fibrosis. Clinical symptoms include abnormal tissue swelling, sensation of limb heaviness, erythema, pain, and impaired limb function.

The added value of manual lymph drainage, applied in patients with mild (early) lower limb lymphoedema and in addition to skin care, exercises and a compression stocking, has never been investigated.

Therefore, the objective of this randomised controlled pilot trial is to investigate the feasibility of a trial about the added value of manual lymph drainage (to skin care, exercises and wearing compression stocking) in patients with mild (early) lower limb lymphoedema. In fact, the investigators want to determine the sample size for a trial investigating the effectiveness of MLD and want to investigate the feasibility of the study design.

Lymphoedema and Nocturia/ Nocturnal Polyuria After Pelvic Lymph Node Dissection for Urogenital Cancer

Lymphoedema and Nocturia/ Nocturnal Polyuria After Pelvic Lymph Node Dissection (LND) for Urogenital Cancer: Randomised Controlled Trial (Pilot)

Lymphoedema-specific quality of life will be evaluated using the Lymph-ICL-LL questionnaire: The Lymph-ICF-LL is a descriptive, evaluative tool containing 28 questions about impairments in function, activity limitations, and participation restrictions in patients with lower limb lymphoedema. The questionnaire has 5 domains: physical function, mental function, general tasks/household activities, mobility activities, and life domains/social life.

Volume measurements will be done at midline, leg and foot. Volume midline: circumference at the level of the hip and distance navel - pubic bone, with tapeline.

Volume leg: circumference measurements in sitting position, with knee extension, foot supported by chair; reference point is the upper border of the patella and every 4cm up to the groin and to the ankle, with perimeter Volume foot: figure of 8 method: in sitting position, with knee extension, foot supported by chair and relaxed; with tapeline; make the figure 8 between the distal part of medial and lateral malleolus and the proximal border of metatarsal I and V

Health-related quality of life will be assessed with the EuroQol EQ-5D-5L (questionnaire).

The EQ-5D, developed by the EuroQol Group, is a generic HRQoL instrument commonly used for indirect utility measurement. It is a descriptive system for health states, encompassing 5 dimensions of health (mobility, self-care, usual activities, pain/discomfort and anxiety/depression), combined with a visual analogue scale ranging from "worst imaginable health state" to "best imaginable health state". Each health dimension has 5 levels of severity (EQ-5D-5L;5L: no problems, slight problems, moderate problems, severe problems,extreme problems /unable to).

Each EQ-5D health state is labelled by a code, e.g. 21531, where each digit represents the severity level of a dimension. By convention, the order of dimensions is mobility, self-care, usual activities, pain/discomfort and anxiety/depression.

Physical activity will be assessed with the International Physical Activity Questionnaire (IPAQ).

The IPAQ is a 27-item self-reported measure of physical activity for use with individual adult patients aged 15 to 69 years old.

Water content in the leg and midline region will be measured using the MoistureMeterD Compact.

Extracellular fluid in the lower limb will be measured with bio-impedance spectroscopy.

Body weight will be measured with an electronic balance

Number of infection episodes during the previous 6 months is questioned

Number of patients accepting to participate in the randomized controlled pilot trial

If the participant is randomised to the intervention group with manual lymph drainage, information is collected regarding the type of lymph drainage, the number of sessions and the duration of one session.

Difficulties concerning the intervention will be registered

The number of drop-outs in both the experimental as the control group

Rare Diseases

Carcinoma

Carcinoma, Renal Cell

Kidney Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Urologic Neoplasms

Kidney Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Anti-Infective Agents

Bevacizumab

Sirolimus

Interferons

Interferon-alpha

Temsirolimus

MTOR Inhibitors

Angiogenesis Inhibitors

Growth Inhibitors

Antiviral Agents

Immunologic Factors

Protein Kinase Inhibitors

Enzyme Inhibitors

Immunosuppressive Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Clotrimazole

Miconazole

Antifungal Agents

Bevacizumab 10 mg/kg intravenous (IV) q8wks + Temsirolimus 25 mg IV weekly

Bevacizumab 10 mg/kg intravenous (IV) q8wks + Interferon-Alfa 9MU SC TIW

Bevacizumab 10 mg/kg intravenous (IV) q8wks

Interferon-Alfa 9MU

Pfizer CT.gov Call Center

Primary objective: Comparison of independently assessed progression free survival (PFS) in subjects administered Bevacizumab + Temsirolimus vs. those administered Bevacizumab + Interferon-Alfa. Secondary objectives: safety, Investigator assessed PFS, objective response rate (independently assessed), and overall survival.

Study Comparing Bevacizumab + Temsirolimus vs. Bevacizumab + Interferon-Alfa In Advanced Renal Cell Carcinoma Subjects

Phase 3b, Randomized, Open-Label Study Of Bevacizumab + Temsirolimus Vs. Bevacizumab + Interferon-Alfa As First-Line Treatment In Subjects With Advanced Renal Cell Carcinoma

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Adoptive Cell Therapy Using Cancer Specific CD8+ Tumor Infiltrating Lymphocytes in Adult Patients With Solid Tumors	NCT05902520	HNSCC Melanoma Gynecologic Can... Colorectal Canc... Lung Cancer Urogenital Canc...	DP CD8 TIL DP CD8 TIL KD Low dose IL-2	18 Years -	AgonOx, Inc.
Development of a Clinical Screening, Diagnostic and Evaluation Tool for Patients With Lower Limb Lymphedema: Aim 2	NCT05421377	Lower Limb Lymp...	clinical assess...	18 Years -	KU Leuven
Adoptive Cell Therapy Using Cancer Specific CD8+ Tumor Infiltrating Lymphocytes in Adult Patients With Solid Tumors	NCT05902520	HNSCC Melanoma Gynecologic Can... Colorectal Canc... Lung Cancer Urogenital Canc...	DP CD8 TIL DP CD8 TIL KD Low dose IL-2	18 Years -	AgonOx, Inc.
Two Bed SPECT/CT Versus Planar Bone Scintigraphy in Detection of Osseous Metastases in Patients With Genitourinary Malignancies	NCT05597215	Bone Metastases Urogenital Canc...	Tc-99m MDP and ...	18 Years -	Assiut University
Lymphoedema and Nocturia/Nocturnal Polyuria After Pelvic LND for Urogenital Cancer	NCT05300308	Urogenital Canc... Lower Limb Lymp... Nocturia Nocturnal Polyu...	usual care	18 Years -	Universitaire Ziekenhuizen KU Leuven
Neoadjuvant Immune Checkpoint Inhibitor Treatment in Urothelial Cancer	NCT04624399	Urogenital Canc...	Atezolizumab	18 Years - 99 Years	Queen Mary University of London
Lymphoedema and Nocturia/ Nocturnal Polyuria After Pelvic Lymph Node Dissection for Urogenital Cancer	NCT05266157	Lower Limb Lymp... Urogenital Canc...	Manual lymph dr... Usual care	18 Years -	Universitaire Ziekenhuizen KU Leuven
Study Comparing Bevacizumab + Temsirolimus vs. Bevacizumab + Interferon-Alfa In Advanced Renal Cell Carcinoma Subjects	NCT00631371	Renal Cell Carc...	Bevacizumab Temsirolimus Bevacizumab Interferon-Alfa...	18 Years -	Pfizer
Bintrafusp Alfa (M7824) and NHS-IL12 (M9241) Alone and in Combination With Stereotactic Body Radiation Therapy (SBRT) in Adults With Metastatic Non-Prostate Genitourinary Malignancies	NCT04235777	Urothelial Canc... Bladder Cancer Genitourinary C... Urogenital Neop... Urogenital Canc...	M7824 M9241 Stereotactic bo...	18 Years -	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for urogenital cancer