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

Digestive System Diseases

Rectal Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Intestinal Diseases

Rectal Diseases

Drug name: Sodium Copper Chlorophyllin Dosage form: Tablet Dosage: 750 mg Route of administration: Oral Frequency: Once daily in the morning before food. Duration: From 10-14 days before radiotherapy up to 3 months after the last dose of cytotoxic therapy

Drug Name: Placebo Dosage form: 1 Tablet Route of administration: Oral Frequency: Once daily in the morning before food. Duration: From 10-14 days before radiotherapy up to 3 months after the last dose of cytotoxic therapy

Additional Chlorophyllin tablet with Short Course radiotherapy based total neoadjuvant treatment +/- brachytherapy boost dose

Chlorophyllin, Sodium Copper Complex

Additional Placebo tablet with Short Course radiotherapy based total neoadjuvant treatment +/- brachytherapy boost dose

Placebo

Prof. Rahul Krishnatry, M.D.

Rahul Krishnatry, MD

The goal of this clinical trial is to see, if addition of chlorophyllin to neoadjuvant Chemo-radiotherapy can reduce the gastro-intestinal/genitourinary/hematological toxicity rates and improve the quality of life in patient's diagnosed with locally advanced rectal cancer.

This is a randomized placebo control trial, wherein participants randomized to Chlorophyllin arm will receive the drug of interest along with the standard treatment. Participants randomized to other arm will receive placebo along with the standard treatment.

Researchers will compare the difference between the outcomes from both the arms and will also observe the non-operative management success rates.

The current standard treatment for locally advanced rectal cancer includes neoadjuvant (treatment given before Surgery) radiotherapy \& chemotherapy followed by surgery if needed or wait and watch in patients whom tumour has completely regressed. It has been observed that even after receiving this intensive treatment patients, almost 70% of patients develop acute toxicity (during or within 3 months) of grade 2 or higher (needing medication for toxicity). This affects their treatment tolerance, completion and quality of life.

In this study Researchers are going to see if addition of drug Chlorophyllin (derived from green plant leaves) along with standard treatment would help in reducing the acute toxicity. This is a randomized study which has two arms; Arm 1 is test arm where participants will receive drug of interest (Chlorophyllin) and in other arm participants will receive Placebo. Upon successful completion of study, outcomes from both the study arm will compared and participants will be followed by standard protocol for 2 years.

SCRT in TNT With or Without Chlorophyllin

Short Course Radiotherapy Based Total Neoadjuvant Therapy With Or Without Chlorophyllin (SCOTCH Study)

Incidence of grade 2 or higher Common Terminology Criteria for Adverse Events (CTCAE) acute gastro-intestinal (GI)/genitourinary (GI)/haematological toxicity (HT).

Minimum value: Grade 1 Maximum value: Grade 5 Grade 1 late toxicity means a good outcome. Grade 2 or higher late toxicity means a worse outcome.

To estimate the 2-year overall complete response rates (clinical or pathological) in whole cohort and if any difference between chlorophyllin and control arms.

To estimate the 2-year organ preservation rates by estimating patients who did not need surgery for rectal cancer (Total mesorectal excision; TME) at two years and if any difference between chlorophyllin and control arms.

To estimate the 2-year disease free survival, Distant metastasis free survival, loco-regional failure free survival, and overall survival rates in the whole cohort, and if any difference between two arms and between patients with successful non-operative management versus others.

To compare treatment-related early and late toxicities (grade 2 Common Terminology Criteria for Adverse Events, version 5.0) for two years between the groups as (3).

Minimum value: Grade 1 Maximum value: Grade 5 Grade 1 late toxicity means a good outcome. Grade 2 or higher late toxicity means a worse outcome.

To estimate surgical complications based on Clavien-Dindo classification. Minimum value: Grade 1 Maximum value: Grade 5 Grade 1 surgical complications means a good outcome. Grade 2 or higher surgical complications means a worse outcome.

To estimate and compare Health Related Quality of Life (QOL) between various groups as (3). using quality of life questionnaires (QLQ) of European Organization for Research and Treatment of Cancer (EORTC) These questionnaires will be filled by patient at six month interval of follow up.

The direct cost of per patient for various supportive medications, hospital admissions will be estimated in both arms and compared to see if any financial benefit of reduction in toxicity.

Record of medicines and details of hospitalization will be maintained.

To study the correlation of tumour volume with used radiotherapy doses leading to a successful non-operative management versus not in the study group of patients.

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
SCRT in TNT With or Without Chlorophyllin	NCT05856305	Rectal Neoplasm...	Chlorophyllin, ... Placebo	18 Years - 90 Years	Tata Memorial Centre

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