Urinary Tract, Sexual Organs, and Pregnancy Conditions

Symptoms and General Pathology

All Conditions

Neoplasms

Urinary Bladder, Overactive

Urinary Bladder Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

Lower Urinary Tract Symptoms

Urological Manifestations

All Drugs and Chemicals

Cholinergic Antagonists

Cholinergic Agents

Neurotransmitter Agents

Questionnaires, anticholinergic treatment, urodynamic study

Michael Vainrib, MD

Bladder carcinoma is the most common malignancy of the urinary tract. Approximately 75-85% of patients with bladder cancer present with a disease that is confined to the mucosa or submucosa. These categories are grouped as non-muscle-invasive bladder tumors(i.e. superficial tumors).

Bladder cancer is the fifth most common cancer in the United States, with an estimated 67,160 newly diagnosed cases and 13,750 deaths in the United States in 2007. The 5-year survival rate is 82% for all stages combined. The standard of treatment for patients with superficial bladder cancer is surgical transurethal resection (TUR) of tumors, with an 80% early success rate. However, nearly 70% of these patients will develop tumor recurrence, with 25% showing progression to muscle-invading disease, within 5 years with TUR.

It is therefore necessary to consider adjuvant therapy in all patients. The absolute risks of recurrence and progression do not always indicate the risk at which a certain therapy is optimal. The choice of therapy may be considered differently according to what risk is acceptable for the individual patient and the urologist.

Intravesical chemotherapy and immunotherapy are widely used as adjuvant therapies after TUR, to prevent recurrence and progression of superficial disease. Systemic therapy is typically reserved for higher stage, muscle-invading, or metastatic diseases. The urinary bladder is an ideal organ for regional therapy.

The urethra provides easy access of therapeutic agents to the urinary bladder. The presence of the specialized asymmetric unit membrane on the urothelium serves as a barrier and limits the absorption of molecules or particulates into the systemic circulation.

The rationale for intravesical therapy is to maximize the exposure of tumors located in the bladder cavity to therapeutics agents while limiting the systemic exposure and thereby limiting the host toxicities; the primary goal is to eradicate existing or residual tumors through direct cytoablation or immunostimulation. The unique properties of the urinary bladder render it a fertile ground for evaluating novel approaches to regional therapy, including local hyperthermia, co-administration of permeation enhancers, bioadhesive carriers, and gene therapy.

One of the developing treatments for high-risk superficial bladder cancers is the combination of intravesical chemotherapy and hyperthermia (HT), called chemohyperthermia (C-HT). The most common form of C-HT uses the Synergo HT system, in which local HT is administered via direct microwave irradiation of the urothelium by means of a 915-MHz intravesical microwave applicator. The target intravesical temperature is set between 41.8C and 44.8C and is measured by five thermocouples integrated in a 20-F treatment catheter. To avoid injury, the urethra is continuously cooled. Due to extensive global experience with its use and a significant amount of preclinical data demonstrating improved antineoplastic efficacy when heated, mitomycin C (MMC) is the most common intravesical chemotherapy agent used in conjunction with HT.

The most common adverse events during treatment were bladder spasms and bladder pain. Literature reports bladder spasms in 21.6% of patients, and bladder pain in 17.5%. Bladder spasms tended to occur more frequently with the prophylactic schedule, whereas pain was present equally in the prophylactic and ablative schedules but more commonly after the ablative schedule. In the first days following C-HT, storage LUTS (frequency, dysuria, urgency, nocturia) (25.6%) and hematuria (6.0%) are the most common adverse events. Most studies mention that these symptoms were mild and transient, resolving spontaneously within a few days of treatment. One study described severe cystitis complaints in three patients (16%), but other studies have not confirmed these adverse events. Two studies report the development of a contracted bladder and severe urinary incontinence after ablative C-HT. However, the possibility cannot be excluded that previous transurethral resection and intravesical chemotherapy might have contributed to this event.

Following the appearance of bothersome storage LUTS, patient should be managed by existing guidelines. Based on AUA/SUFU Diagnosis and Treatment of Overactive Bladder (Non-Neurogenic) in Adults Guidelines published in 2012 patients should be diagnosed, followed and treated according to the suggested algorithm.

In our study, we would like to assess the severity of OAB symptoms and their response to a standard OAB treatment according to AUA Guidelines for Non-neurogenic OAB as well as to assess urodynamic study variables in those who didn't respond to a standard medical treatment and bothered by their OAB symptoms.

Severity of Overactive Bladder Symptoms in Patients After Synergo Treatment

Severity of Overactive Bladder Symptoms in Patients After Synergo Treatment for Bladder Cancer

OAB-SS, OAB-Q, OAB-SQ - questionnaires Urodynamic study results in patients who will undergo the test

relationship between the answers in OAB-SS, OAB-Q, OAB-SQ - questionnaires, Urodynamic study results in patients who will undergo the test and type of Synergo protocol, number of treatments received, time of hyperthermia per treatment, bladder cancer stage at the beginning of Synergo treatment.

OAB-SS, OAB-Q, OAB-SQ - questionnaires and relationship to Urodynamic study results in patients who will undergo the urodynamic test

OAB-SQ - questionnaire and urodynamic study results

Meir Medical Center

Wounds and Injuries

Carcinoma

Carcinoma, Papillary

Carcinoma in Situ

Hyperthermia

Fever

Non-Muscle Invasive Bladder Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Antineoplastic Agents

Anti-Infective Agents

Mitomycins

Mitomycin

BCG Vaccine

Anti-Bacterial Agents

Antibiotics, Antitubercular

Alkylating Agents

Enzyme Inhibitors

Bladder radiofrequency-induced hyperthermia will be delivered in combination with each instillation of MMC in accordance with the Sponsor operational guidelines.

Subjects will receive a series of induction followed by a series of maintenance bladder instillations of Synergo® RITE + MMC

Synergo® RITE + MMC

Michael A O'Donnell, MD

This study will determine whether Synergo® RITE + MMC treatment is efficacious as second-line therapy for CIS NMIBC BCG-unresponsive patients with or without papillary NMIBC, through examination of the complete response rate (CRR) and disease-free duration for complete responders. The study will also explore progression-free survival time, bladder preservation rate, and overall survival time.

The study will address an unmet need to identify a treatment effective in both ablating the disease and providing a prolonged disease-free period for patients. Ideally, the treatment will delay progression to invasive disease, thus preserving the bladder.

Mitomycin C Intravesical Chemotherapy in Conjunction With Synergo® Radiofrequency-Induced Hyperthermia for Treatment of Carcinoma in Situ Non-Muscle Invasive Bladder Cancer Patients Unresponsive to Bacillus Calmette-Guérin, With or Without Papillary Tumors.

A Multicenter, Single-Arm Study Evaluating the Efficacy of Synergo® Radiofrequency-Induced Thermochemotherapy Effect (RITE) With Mitomycin C (Synergo® RITE + MMC) in CIS Non-Muscle Invasive Bladder Cancer (NMIBC) Bacillus Calmette-Guérin (BCG)-Unresponsive Patients With or Without Papillary NMIBC

* no CIS
* no papillary HG tumor
* no papillary T1 tumor
* no extra-vesical UC tumor
* no progression

a patient will be considered a complete responder only if all the criteria above are met.

Patients experiencing a new occurrence of a benign tumor or low-grade Ta will be allowed to continue in the study (tumor will be resected); such an occurrence will not constitute an event in the primary analysis.

Patients with tumors of the ostium and/or upper tract and/or prostatic urethra will be considered to have achieved a complete response in the primary analysis but will be removed from the study.

time of recurrence for complete response patients from the 3-month visit until the time of recurrence or until the last follow-up, whichever occurs sooner.

Medical Enterprises Ltd.

Behaviors and Mental Disorders

Body Temperature Changes

Stress Disorders, Traumatic

Heat Stress Disorders

Vaccines

Adjuvants, Immunologic

Immunologic Factors

Synergo radiofrequency (RF)-Induced hyperthermia-chemotherapy (SHTC) with mitomycin C (RITE) intravesical therapy as first-line adjuvant treatment for intermediate and high-risk NMIBC,

Intravesical BCG therapy as first-line adjuvant treatment for intermediate and high-risk NMIBC,

Synergo radiofrequency (RF)-Induced hyperthermia-chemotherapy with mitomycin C (RITE). Intravesical instillation of MMC utilizing the Synergo system.

Synergo + MMC

Bacillus Calmette-Guérin

Igal Ruvinsky, PhD

Gerson Luedecke, Dr. med.

A multi-institutional, prospective, randomised, open-label, superiority, comparative, active-controlled, phase 3 study. The study will compare Synergo RF-induced hyperthermia-chemotherapy (SHTC) plus mitomycin C (MMC) to standard treatment of bacillus Calmette-Guérin (BCG) therapy as first-line adjuvant treatment for intermediate and high-risk NMIBC, and will evaluate recurrence and progression rate over two years of follow-up.

SHTC - EUROPE-1 Synergo Hyperthermia-Chemotherapy by European Urologists' Research Operation Preserving Evolution Study I

A Multi-Centre, Randomised, Open-Label Active-Controlled Study Comparing Safety and Efficacy of Synergo Radiofrequency (RF)-Induced Hyperthermia-Chemotherapy With Mitomycin C (RITE) Versus Bacillus Calmette-Guérin (BCG) as First-Line Treatment of Non-Muscle Invasive Papillary Bladder Cancer (NMIBC)

The recurrence-free survival time in patients with NMIBC following treatment with SHTC (investigational arm) compared to BCG (controlled arm).

Safety (rate of adverse events), as well as tolerability of SHTC compared to BCG in terms of the frequency, severity and nature of adverse events and the treatment received.

Proportion of treatment discontinuation of SHTC compared to BCG

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Severity of Overactive Bladder Symptoms in Patients After Synergo Treatment	NCT01955408	Overactive Blad... Bladder Cancer Synergo	Questionnaires,...	18 Years -	Meir Medical Center
Mitomycin C Intravesical Chemotherapy in Conjunction With Synergo® Radiofrequency-Induced Hyperthermia for Treatment of Carcinoma in Situ Non-Muscle Invasive Bladder Cancer Patients Unresponsive to Bacillus Calmette-Guérin, With or Without Papillary Tumors.	NCT03335059	Bladder Cancer Bladder Neoplas... Bladder Tumors Cancer of Bladd... Cancer of the B... Malignant Tumor... Neoplasms, Blad... Urinary Bladder... Carcinoma in Si... Papillary Carci... BCG-Unresponsiv...	Synergo® RITE +...	18 Years -	Medical Enterprises Ltd.
SHTC - EUROPE-1 Synergo Hyperthermia-Chemotherapy by European Urologists' Research Operation Preserving Evolution Study I	NCT02254915	Urinary Bladder... Urologic Neopla... Urogenital Neop... Neoplasms Neoplasms by Si... Urinary Bladder... Urologic Diseas...	Synergo + MMC Bacillus Calmet...	18 Years -	Medical Enterprises Europe B.V.
Severity of Overactive Bladder Symptoms in Patients After Synergo Treatment	NCT01955408	Overactive Blad... Bladder Cancer Synergo	Questionnaires,...	18 Years -	Meir Medical Center
Severity of Overactive Bladder Symptoms in Patients After Synergo Treatment	NCT01955408	Overactive Blad... Bladder Cancer Synergo	Questionnaires,...	18 Years -	Meir Medical Center
SHTC - EUROPE-1 Synergo Hyperthermia-Chemotherapy by European Urologists' Research Operation Preserving Evolution Study I	NCT02254915	Urinary Bladder... Urologic Neopla... Urogenital Neop... Neoplasms Neoplasms by Si... Urinary Bladder... Urologic Diseas...	Synergo + MMC Bacillus Calmet...	18 Years -	Medical Enterprises Europe B.V.
Mitomycin C Intravesical Chemotherapy in Conjunction With Synergo® Radiofrequency-Induced Hyperthermia for Treatment of Carcinoma in Situ Non-Muscle Invasive Bladder Cancer Patients Unresponsive to Bacillus Calmette-Guérin, With or Without Papillary Tumors.	NCT03335059	Bladder Cancer Bladder Neoplas... Bladder Tumors Cancer of Bladd... Cancer of the B... Malignant Tumor... Neoplasms, Blad... Urinary Bladder... Carcinoma in Si... Papillary Carci... BCG-Unresponsiv...	Synergo® RITE +...	18 Years -	Medical Enterprises Ltd.

Spots Global Cancer Trial Database for synergo

Every month we try and update this database with for synergo 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.

Spots Global Cancer Trial Database for synergo

Every month we try and update this database with for synergo 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.

Every month we try and update this database with for synergo 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.