Neoplasms

Symptoms and General Pathology

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Neoplasm Metastasis

Hemorrhage

Cystitis

Cystitis, Hemorrhagic

Urinary Bladder Diseases

Urologic Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Male Urogenital Diseases

Anti-Infective Agents

All Drugs and Chemicals

Anti-Inflammatory Agents

Micronutrients

Mineral

Anti-Bacterial Agents

Antioxidants

Antiviral Agents

Copper

Chlorophyllin

Trace Elements

Protective Agents

Copper Supplement

Participants will receive oral Sodium Copper Chlorophyllin at a dose of 750mg once daily (OD) on an empty stomach.

Sodium-copper-chlorophyllin (CHL) is a phytopharmaceutical drug obtained from green plant pigment, chlorophyll. Chlorophyllin scavenges radiation-induced free radicals and reactive oxygen species. It is used as a food colorant and OTC in the USA, Japan, Australia and China for many years for a variety of health benefits including prevention of body odour in geriatric patients, enhanced wound healing, antibacterial action, prevention of cancer in the high-risk populations exposed to hepatocarcinogen aflatoxin B1, treatment of faecal incontinence etc. Studies have shown that CHL has immunostimulatory, anti-inflammatory and antiviral effects in addition to antioxidant and radioprotective properties. It increases the expression of a transcription factor (protein) Nrf2 which improves lymphocyte survival and enables efficient detoxification after exposure to radiation. The duration of therapy will be up to 6 months depending upon the response of participants.

Sodium Copper Chlorophyllin

Dr. Gagan Prakash

Dr. Vikram Gota

Dr. Vedang Murthy

Dr. Amit Joshi

Dr. Mahendra Pal

Dr. Priyamvada Maitre

Dr. Supriya Sastri

Dr. Santosh Menon

Dr. Nilesh Sable

Dr. Aparna Katdare

To assess the efficacy of oral chlorophyllin tablets for urinary bleeding following radiation therapy for cancers of pelvic organs.

Radiation therapy to the pelvis is a commonly used treatment modality for urological, gynaecological and rectal cancers. Intensity modulation and image guidance have improved the delivery of radiation therapy in recent times. However, this does not eliminate the risk of radiation-induced damage to the adjacent healthy tissue - in this consideration, the bladder. Hemorrhagic cystitis accounts for 5-7% of emergency urology admissions. The procedure for the management of radiation cystitis proceeds from non-invasive oral drugs and HBOT to minimally invasive treatment like intravesical therapy and angioembolization, to more morbid procedures like cystectomy and urinary diversion. Although these treatment modalities have shown some success, most patients continue to have recurrent/persistent hematuria. There is a need to explore options of other oral/intravesical agents which can aid in mucosal healing and stop hematuria with lasting effects. Sodium-copper-chlorophyllin (CHL) is a phytopharmaceutical drug obtained from green plant pigment, chlorophyll. It is a semi-synthetic mixture of sodium copper salts derived from chlorophyll. Chlorophyllin scavenges radiation-induced free radicals and reactive oxygen species. Research at BARC has shown that chlorophyllin prevents radiation-induced toxicity in normal hematopoietic tissues and normal epithelial cells. A phase 1 clinical study in healthy volunteers indicate that CHL is safe and tolerable in humans and has not shown any severe adverse events. The purpose of this study is to evaluate the safety and efficacy of oral sodium copper chlorophyllin in hemorrhagic cystitis secondary to radiation therapy for pelvic malignancy.

A prospective, single centre, single-arm, interventional phase II study.

Chlorophyllin Tablets for Urinary Bleeding Following Radiation Therapy for Cancers of Pelvic Organs

A Phase II Study to Evaluate Oral Chlorophyllin in Hemorrhagic Cystitis Secondary to Radiation Therapy for Pelvic Malignancies

All study-related information will be strictly maintained and will be shared only with the IEC and DSMB authorities.

Objective Response Rate (ORR) The proportion of patients with CR/PR.The ORR will be determined as below.Complete response(CR):resolution of hematuria (gross/macroscopic hematuria for grade II/III and microscopic hematuria for grade I hemorrhagic cystitis) Partial response(PR):improvement (decrease by at least 1 grade of hemorrhagic cystitis but not complete resolution of hematuria over 3 months from the start of treatment.The grading of hemorrhagic cystitis will be as per the CTCAE v5.0.

Bladder cancer index (BCI) scores will be calculated at baseline, 1 month and 3 months for each study participant.

Minimum value - 0, Maximum value - 100, Higher scores depict better outcome.

Treatment Failure (TF) defined as requirement of alternative intervention for persistent severe hematuria within 3 months from the start of treatment or early stoppage due to intolerable side effects in the absence of PR/CR \[Intervention: multiple cystoscopies with clot evacuation, cystectomy, hyperbaric oxygen therapy (HBOT) or transfusion due to persistent drop in hemoglobin\].

Treatment failure-free survival is defined as the time from enrolment to the date of first intervention up to 3 months or date of discontinuation of therapy due to intolerable side effects in the absence of PR/CR.

QoL will be measured using the EORTC-QLQ-30 questionnaire at baseline, 1 month and 3 months for each study participant.

Minimum value - 0, Maximum value cannot be predetermined. five functional scales (physical, role, cognitive, emotional, and social), three symptom scales (fatigue, pain, and nausea and vomiting), a global health status / QoL scale, and a number of single items assessing additional symptoms commonly reported by cancer patients (dyspnoea, loss of appetite, insomnia, constipation and diarrhoea) and perceived financial impact of the disease. Therefore, higher scores depict better outcomes for some scales whereas for some scales lower scores depict better outcomes.

Bhabha Atomic Research Centre (BARC), Mumbai

Tata Memorial Centre

Professor, Urologic Oncology

Nutritional and Metabolic Diseases

Nervous System Diseases

Syndrome

Urinary Bladder Neoplasms

Malnutrition

Pain

Urinary Bladder, Neurogenic

Endometriosis

Cystitis, Interstitial

Genital Diseases, Female

Genital Diseases

Neurologic Manifestations

Seven days of preoperative oral supplementation with an immune-enhanced oral nutrition

Immunonutrition: Oral Impact®, Nestlé Health Science, Switzerland.

IN will be administered as per manufacturer suggestion, i.e. three times a day during 7 days preoperatively. Oral Impact® is a powdered oral feed that provides 309 kcal/bag

Immunonutrition

Ilaria Lucca, MD

François Crettenand, MD

Bernhard Kiss, MD

Thomas Tawadros, PhD

The goal of this clinical trial research study is to evaluate the impact of preoperative oral immunonutrition (IN) on post-operative complications in patients undergoing a cystectomy.

As a secondary focus, this study will aim to develop a signature that would identify patients that would benefit the most from IN.

This is a multicentric (Swiss: N=3), prospective, controlled, pragmatic, parallel-group comparative study with block randomization stratified by centers.

Despite standardized surgical technique and the development of new perioperative care protocols, cystectomy morbidity remains a serious challenge for urologists. Most common postoperative complications, such as infections, often lead to longer length of stay and worse survival. Malnutrition has been identified as an independent and modifiable risk factor for both mortality and morbidity. Immunonutrition (IN), containing arginine, ribonucleic acid and omega-3 polyunsaturated fatty acids, aims to improve the nutritional status, immunological function and clinical outcome of surgical patients. Meta-analyses have demonstrated that preoperative IN reduces complications and length of hospital stay after major bowel surgery. Evidence-based data on preoperative oral IN support for cystectomy patients are lacking, which does not allow this treatment to be widely accepted, recommended, or reimbursed by health insurances in most European countries. Uncertainties also remain about the exact mechanism by which IN modulates the host immune response.

Complication rates after cystectomy range from 40-75%. Malnutrition has been identified as an independent and modifiable risk factor for both mortality and morbidity. To date, and in the last 20 years, no single intervention has allowed for a significant reduction in morbidity after cystectomy, which remains one of the highest in surgery. The present adequately powered multicenter RCT has the potential of changing current practice by recommending preoperative IN before cystectomy in case of positive results. If the present RCT demonstrates a benefit in administrating IN prior to cystectomy, urological guidelines will be modified accordingly to this new evidence. IN will then be recommended before cystectomy for the patient's benefit. The investigators truly believe that the proposed study is of high clinical importance with potential impact on perioperative urology guidelines.

Multicenter, prospective, controlled, pragmatic, parallel-group comparative study with block randomization stratified by centers

The Role of Preoperative Immunonutrition on Morbidity and Immune Response After Cystectomy (INCyst Trial)

The Role of Preoperative Immunonutrition on Morbidity and Immune Response After Cystectomy - A Multicenter Randomized Controlled Trial (INCyst Trial)

Long term overall and cancer-specific survival for bladder cancer patients

Assessment of the quality of life after surgery through a questionnaire (EORTC QLQ-C30)

Identification of biomarkers predictive of postoperative complications studying the patient's immune and microbiome signature: analysis of immune cells in the blood, analysis of the polyfunctionality of blood T cells, analysis of immune-related proteins in the urine and serum, microbiota analysis, expression of Argininosuccinate synthetase 1

Determination of infectious complications rate at 30 days after surgery (pneumonia, urinary tract infection, surgical site infection, sepsis, shock).

Determination of the Comprehensive Complication Index (CCI) at 30 and 90 days after surgery. The range is between 0 (no complication) to 100 (death).

Determination of the mortality rate at 30 and 90 days after surgery

Determination of the post-operative complication-free survival

Serum arginine levels will be assessed at enrolment (between Day -30 and Day -10) and at preoperative admission after intake of the allocated nutrition (Day -1) in all patients treated at Lausanne, CHUV.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Chlorophyllin Tablets for Urinary Bleeding Following Radiation Therapy for Cancers of Pelvic Organs	NCT05348239	Hemorrhagic Cys...	Sodium Copper C...	18 Years -	Tata Memorial Centre
Chlorophyllin Tablets for Urinary Bleeding Following Radiation Therapy for Cancers of Pelvic Organs	NCT05348239	Hemorrhagic Cys...	Sodium Copper C...	18 Years -	Tata Memorial Centre
The Role of Preoperative Immunonutrition on Morbidity and Immune Response After Cystectomy (INCyst Trial)	NCT05726786	Bladder Cancer Interstitial Cy... Painful Bladder... Neurogenic Blad... Hemorrhagic Cys... Endometriosis Bladder Disease	Immunonutrition	18 Years -	Centre Hospitalier Universitaire Vaudois
The Role of Preoperative Immunonutrition on Morbidity and Immune Response After Cystectomy (INCyst Trial)	NCT05726786	Bladder Cancer Interstitial Cy... Painful Bladder... Neurogenic Blad... Hemorrhagic Cys... Endometriosis Bladder Disease	Immunonutrition	18 Years -	Centre Hospitalier Universitaire Vaudois

Spots Global Cancer Trial Database for hemorrhagic cystitis